U.S. patent application number 09/774582 was filed with the patent office on 2001-08-09 for substituted cyclopentene derivatives and method for preparing the same.
This patent application is currently assigned to Nissan Chemical Industries, Ltd.. Invention is credited to Sato, Fumie.
Application Number | 20010012907 09/774582 |
Document ID | / |
Family ID | 13378583 |
Filed Date | 2001-08-09 |
United States Patent
Application |
20010012907 |
Kind Code |
A1 |
Sato, Fumie |
August 9, 2001 |
Substituted cyclopentene derivatives and method for preparing the
same
Abstract
A halogenated substituted cyclopentene derivative of formula
(I): 1 wherein R is a hydrogen atom, alkyl radical having 1-6
carbon atoms, alkenyl radical having 2-6 carbon atoms, alkynyl
radical having 2-6 carbon atoms, cycloalkyl radical having 3-8
carbon atoms, aralkyl radical having 7-19 carbon atoms, aryl
radical having 6-12 carbon atoms, alkoxy radical having 1-6 carbon
atoms, alkenyloxy radical having 2-6 carbon atoms, alkylthio
radical having 1-6 carbon atoms or alkenylthio radical having 2-6
carbon atoms; X.sup.1 is (.alpha.-OZ.sup.a, .beta.-H) or
(.alpha.-H, .beta.-OZ.sup.a), X.sup.3 is (.alpha.-OZ.sup.d,
.beta.-H), (.alpha.-H, .beta.-OZ.sup.d) or oxygen atom, each of
Z.sup.a and Z.sup.d, which may be the same or different, is a
hydrogen atom or a protective radical for a hydroxyl radical; and W
is a halogen atom.
Inventors: |
Sato, Fumie; (Fujisawa-shi,
JP) |
Correspondence
Address: |
BIRCH STEWART KOLASCH & BIRCH
PO BOX 747
FALLS CHURCH
VA
22040-0747
US
|
Assignee: |
Nissan Chemical Industries,
Ltd.
|
Family ID: |
13378583 |
Appl. No.: |
09/774582 |
Filed: |
February 1, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09774582 |
Feb 1, 2001 |
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09666602 |
Sep 20, 2000 |
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09666602 |
Sep 20, 2000 |
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09456413 |
Dec 8, 1999 |
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6191291 |
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09456413 |
Dec 8, 1999 |
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09149484 |
Sep 8, 1998 |
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6025518 |
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09149484 |
Sep 8, 1998 |
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08894879 |
Sep 2, 1997 |
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5874634 |
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08894879 |
Sep 2, 1997 |
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PCT/JP96/00422 |
Feb 23, 1996 |
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Current U.S.
Class: |
568/43 ; 568/380;
568/838 |
Current CPC
Class: |
C07F 7/1804 20130101;
Y02P 20/55 20151101; C07C 69/738 20130101; C07C 405/00 20130101;
C07C 2601/10 20170501 |
Class at
Publication: |
568/43 ; 568/380;
568/838 |
International
Class: |
C07C 049/597; C07C
323/22 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 2, 1995 |
JP |
7-68605 |
Claims
1. A halogenated substituted cyclopentene derivative of the formula
(I): 73 wherein R is a hydrogen atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, aralkyl radical having 7 to 19 carbon atoms, aryl
radical having 6 to 12 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms,
alkylthio radical having 1 to 6 carbon atoms or alkenylthio radical
having 2 to 6 carbon atoms; X.sup.1 is (.alpha.-OZ.sup.a, .beta.-H)
or (.alpha.-H, .beta.-OZ.sup.a), X.sup.3 is (.alpha.-OZ.sup.d,
.beta.-H), (.alpha.-H, .beta.-OZ.sup.d) or oxygen atom, each of
Z.sup.a and Z.sup.d, which may be the same or different, is a
hydrogen atom or a protective radical for a hydroxyl radical; and W
is a halogen atom.
2. A method for preparing a halogenated substituted cyclopentene
derivative of the formula (I): 74 wherein R, X.sup.1, X.sup.3, and
W are as defined below, said method comprising the step of reacting
a substituted cyclopentane derivative of the formula (II): 75
wherein R is a hydrogen atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, cycloalkyl radical having 3 to 8 carbon
atoms, aralkyl radical having 7 to 19 carbon atoms, aryl radical
having 6 to 12 carbon atoms, alkoxy radical having 1 to 6 carbon
atoms, alkenyloxy radical having 2 to 6 carbon atoms, alkylthio
radical having 1 to 6 carbon atoms or alkenylthio radical having 2
to 6 carbon atoms; X.sup.1 is (.alpha.-OZ.sup.a, .beta.-H) or
(.alpha.-H, .beta.-OZ.sup.a) , X.sup.3 is (.alpha.-OZ.sup.d,
.beta.-H), (.alpha.-H, .beta.-OZ.sup.d) or oxygen atom, Y is
(.alpha.-OZ.sup.c, .beta.-H) or (.alpha.-H, .beta.-OZ.sup.c), and
each of Z.sup.a, Z.sup.c and Z.sup.d, which may be the same or
different, is a hydrogen atom or a protective radical for a
hydroxyl radical, with a halide of the formula (III):
M.sup.1W.sub.h (III) wherein M.sup.1 is a metal atom selected from
the group consisting of an alkali metal, alkaline earth metal,
first transition metal, Al, Zr, and Ce, or quaternary ammonium, W
is a halogen atom, and h representative of the valence of said
metal or quaternary ammonium is an integer of 1 to 4, or a hydrate
thereof in the presence or absence of a Lewis acid.
3. A method for preparing a substituted cyclopentene derivative of
the formula (V): 76 wherein R, X.sup.1, X.sup.3, U, R.sup.5,
R.sup.6, R.sup.7, R.sup.8, X.sup.2, m, n, p, q, and Z.sup.1 are as
defined below, said method characterized by comprising the step of
reacting a halogenated substituted cyclopentene derivative of the
formula (I): 77 wherein R is a hydrogen atom, alkyl radical having
1 to 6 carbon atoms, alkenyl radical having 2 to 6 carbon atoms,
alkynyl radical having 2 to 6 carbon atoms, cycloalkyl radical
having 3 to 8 carbon atoms, aralkyl radical having 7 to 19 carbon
atoms, aryl radical having 6 to 12 carbon atoms, alkoxy radical
having 1 to 6 carbon atoms, alkenyloxy radical having 2 to 6 carbon
atoms, alkylthio radical having 1 to 6 carbon atoms or alkenylthio
radical having 2 to 6 carbon atoms; X.sup.1 is (.alpha.-OZ.sup.a,
.beta.-H) or (.alpha.-H, .beta.-OZ.sup.a) X.sup.3 is
(.alpha.-OZ.sup.d, .beta.-H), (.alpha.-H, .beta.-OZ.sup.d) or
oxygen atom, each of Z.sup.a and Z.sup.d, which may be the same or
different, is a hydrogen atom or a protective radical for a
hydroxyl radical; and W is a halogen atom with a compound of the
formula (IV):
M.sup.2U.sub.m(CR.sup.5R.sup.6).sub.nX.sup.2.sub.p(CR.sup.7R.sup.8).sub.q-
Z.sup.1 (IV) wherein M.sup.2 is a substituted borane radical,
substituted aluminum radical, substituted zirconium radical or
substituted stannyl radical each having a hydrogen atom, alkyl
radical having 1 to 9 carbon atoms, cycloalkyl radical having 3 to
12 carbon atoms, aralkyl radical having 7 to 10 carbon atoms, aryl
radical having 6 to 8 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, dialkoxy radical having 2 to 12 carbon atoms,
alkenyloxy radical having 2 to 6 carbon atoms, substituted phenoxy
radical, a cyclopentadienyl radical or halogen atom substituent; U
is a radical selected from the group consisting of
CR.sup.1R.sup.2CR.sup.3R.sup.4, CR.sup.1.dbd.CR.sup.3, C.ident.C,
and phenylene wherein R.sup.1 is a hydrogen atom, alkyl radical
having 1 to 9 carbon atoms, alkenyl radical having 2 to 6 carbon
atoms, alkynyl radical having 2 to 6 carbon atoms, cycloalkyl
radical having 3 to 8 carbon atoms, aralkyl radical having 7 to 10
carbon atoms, aryl radical having 6 to 8 carbon atoms, alkoxy
radical having 1 to 6 carbon atoms, alkenyloxy radical having 2 to
6 carbon atoms, halogen atom, substituted silyl radical represented
by SiR.sup.9R.sup.10R.sup.11 or substituted stannyl radical
represented by SnR.sup.14R.sup.15R.sup.16 wherein R.sup.9, R.sup.10
and R.sup.11 are independently selected from the group consisting
of a hydrogen atom, chlorine atom, fluorine atom, alkyl radical
having 1 to 6 carbon atoms, alkenyl radical having 2 to 6 carbon
atoms, alkynyl radical having 2 to 6 carbon atoms, cycloalkyl
radical having 3 to 8 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms, phenyl
radical, tolyl radical, and benzyl radical, R.sup.14, R.sup.15 and
R.sup.16 are independently selected from the group consisting of a
hydrogen atom, chlorine atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, cycloalkyl radical having 3 to 8 carbon
atoms, alkoxy radical having 1 to 6 carbon atoms, alkenyloxy
radical having 2 to 6 carbon atoms, phenyl radical, tolyl radical,
and benzyl radical; R.sup.2, R.sup.3, and R.sup.4 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms; m is an integer of 0
to 6; R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms,
cycloalkyl radical having 3 to 8 carbon atoms, alkoxycarbonyl
radical, and alkenyloxycarbonyl radical; X.sup.2 is
CR.sup.12.dbd.CR.sup.13, C.ident.C, phenylene radical, carbonyl
radical, oxygen atom or sulfur atom wherein R.sup.12 and R.sup.13
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms; p is an
integer of 0 or 1, each of n and q is an integer of 0 to 5; and
Z.sup.1 is a hydrogen atom, COOR.sup.y, CN, OH, OCOR.sup.z,
CONR.sup.bR.sup.c or NR.sup.dR.sup.e wherein R.sup.y and R.sup.z
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms, R.sup.b
and R.sup.c are independently selected from the group consisting of
a hydrogen atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, and cycloalkyl radical having 3 to 8 carbon atoms,
R.sup.d and R.sup.e are independently selected from the group
consisting of a hydrogen atom, benzyl radical, phenyl radical,
alkyl radical having 1 to 6 carbon atoms, alkenyl radical having 2
to 6 carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms, in the presence or
absence of a metal catalyst.
4. A compound of the formula (IV):
M.sup.2U.sub.m(CR.sup.5R.sup.6).sub.nX.-
sup.2.sub.p(CR.sup.7R.sup.8).sub.qZ.sup.1 (IV) wherein M.sup.2 is a
substituted borane radical, substituted aluminum radical,
substituted zirconium radical or substituted stannyl radical each
having a hydrogen atom, alkyl radical having 1 to 9 carbon atoms,
cycloalkyl radical having 3 to 12 carbon atoms, aralkyl radical
having 7 to 10 carbon atoms, aryl radical having 6 to 8 carbon
atoms, alkoxy radical having 1 to 6 carbon atoms, dialkoxy radical
having 2 to 12 carbon atoms, alkenyloxy radical having 2 to 6
carbon atoms, substituted phenoxy radical, a cyclopentadienyl
radical or halogen atom substituent; U is a radical selected from
the group consisting of CR.sup.1R.sup.2CR.sup.3R.sup.4,
CR.sup.1.dbd.CR.sup.3, C.ident.C, and phenylene wherein R.sup.1 is
a hydrogen atom, alkyl radical having 1 to 9 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, cycloalkyl radical having 3 to 8 carbon atoms,
aralkyl radical having 7 to 10 carbon atoms, aryl radical having 6
to 8 carbon atoms, alkoxy radical having 1 to 6 carbon atoms,
halogen atom, substituted silyl radical represented by
SiR.sup.9R.sup.10R.sup.11 or substituted stannyl radical
represented by SnR.sup.14R.sup.15R.sup.16 wherein R.sup.9, R.sup.10
and R.sup.11 are independently selected from the group consisting
of a hydrogen atom, chlorine atom, fluorine atom, alkyl radical
having 1 to 6 carbon atoms, alkenyl radical having 2 to 6 carbon
atoms, alkynyl radical having 2 to 6 carbon atoms, cycloalkyl
radical having 3 to 8 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms, phenyl
radical, tolyl radical, and benzyl radical, R.sup.14, R.sup.15 and
R.sup.16 are independently selected from the group consisting of a
hydrogen atom, chlorine atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, cycloalkyl radical having 3 to 8 carbon
atoms, alkoxy radical having 1 to 6 carbon atoms, alkenyloxy
radical having 2 to 6 carbon atoms, phenyl radical, tolyl radical,
and benzyl radical; R.sup.2, R.sup.3, and R.sup.4 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms; m is an integer of 0
to 6; R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms,
cycloalkyl radical having 3 to 8 carbon atoms, alkoxycarbonyl
radical, and alkenyloxycarbonyl radical; X.sup.2 is
CR.sup.12.dbd.CR.sup.13, C.ident.C, phenylene radical, carbonyl
radical, oxygen atom or sulfur atom wherein R.sup.12 and R.sup.13
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms; p is an
integer of 0 or 1, each of n and q is an integer of 0 to 5; and
Z.sup.1 is a hydrogen atom, COOR.sup.y, CN, OH, OCOR.sup.z,
CONR.sup.bR.sup.c or NR.sup.dR.sup.e wherein R.sup.y and R.sup.z
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms, R.sup.b
and R.sup.c are independently selected from the group consisting of
a hydrogen atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, and cycloalkyl radical having 3 to 8 carbon atoms,
R.sup.d and R.sup.e are independently selected from the group
consisting of a hydrogen atom, benzyl radical, phenyl radical,
alkyl radical having 1 to 6 carbon atoms, alkenyl radical having 2
to 6 carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms.
5. A compound of the formula (V): 78 wherein R is a hydrogen atom,
alkyl radical having 1 to 6 carbon atoms, alkenyl radical having 2
to 6 carbon atoms, alkynyl radical having 2 to 6 carbon atoms,
cycloalkyl radical having 3 to 8 carbon atoms, aralkyl radical
having 7 to 19 carbon atoms, aryl radical having 6 to 12 carbon
atoms, alkoxy radical having 1 to 6 carbon atoms, alkenyloxy
radical having 2 to 6 carbon atoms, alkylthio radical having 1 to 6
carbon atoms or alkenylthio radical having 2 to 6 carbon atoms;
X.sup.1 is (.alpha.-OZ.sup.a, .beta.-H) or (.alpha.-H,
.beta.-OZ.sup.a), X.sup.3 is (.alpha.-OZ.sup.d, .beta.-H),
(.alpha.-H, .beta.-OZ.sup.d) or oxygen atom, each of Z.sup.a and
Z.sup.d, which may be the same or different, is a hydrogen atom or
a protective radical for a hydroxyl radical; U is a radical
selected from the group consisting of
CR.sup.1R.sup.2CR.sup.3R.sup.4, CR.sup.1.dbd.CR.sup.3, C.ident.C,
and phenylene wherein R.sup.1 is a hydrogen atom, alkyl radical
having 1 to 9 carbon atoms, alkenyl radical having 2 to 6 carbon
atoms, alkynyl radical having 2 to 6 carbon atoms, cycloalkyl
radical having 3 to 8 carbon atoms, aralkyl radical having 7 to 10
carbon atoms, aryl radical having 5 to 8 carbon atoms, alkoxy
radical having 1 to 6 carbon atoms, alkenyloxy radical having 2 to
6 carbon atoms, halogen atom, substituted silyl radical represented
by SiR.sup.9R.sup.10R.sup.11 or substituted stannyl radical
represented by SnR.sup.14R.sup.15R.sup.16 wherein R.sup.9, R.sup.10
and R.sup.11 are independently selected from the group consisting
of a hydrogen atom, chlorine atom, fluorine atom, alkyl radical
having 1 to 6 carbon atoms, alkenyl radical having 2 to 6 carbon
atoms, alkynyl radical having 2 to 6 carbon atoms, cycloalkyl
radical having 3 to 8 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms, phenyl
radical, tolyl radical, and benzyl radical, R.sup.14, R.sup.15 and
R.sup.16 are independently selected from the group consisting of a
hydrogen atom, chlorine atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, cycloalkyl radical having 3 to 8 carbon
atoms, alkoxy radical having 1 to 6 carbon atoms, alkenyloxy
radical having 2 to 6 carbon atoms, phenyl radical, tolyl radical,
and benzyl radical; R.sup.2, R.sup.3, and R.sup.4 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms; m is an integer of 0
to 6; R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms,
cycloalkyl radical having 3 to 8 carbon atoms, alkoxycarbonyl
radical, and alkenyloxycarbonyl radical; X.sup.2 is
CR.sup.12.dbd.CR.sup.13, C.ident.C, phenylene radical, carbonyl
radical, oxygen atom or sulfur atom wherein R.sup.12 and R.sup.13
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms; p is an
integer of 0 or 1, each of n and q is an integer of 0 to 5; and
Z.sup.1 is a hydrogen atom, COOR.sup.y, CN, OH, OCOR.sup.z,
CONR.sup.bR.sup.c or NR.sup.dR.sup.e wherein R.sup.y and R.sup.z
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms, R.sup.b
and R.sup.c are independently selected from the group consisting of
a hydrogen atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, and cycloalkyl radical having 3 to 8 carbon atoms,
R.sup.d and R.sup.e are independently selected from the group
consisting of a hydrogen atom, benzyl radical, phenyl radical,
alkyl radical having 1 to 6 carbon atoms, alkenyl radical having 2
to 6 carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms.
6. A substituted cyclopentene derivative of the formula (VII): 79
wherein R is a hydrogen atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, cycloalkyl radical having 3 to 8 carbon
atoms, aralkyl radical having 7 to 19 carbon atoms, aryl radical
having 6 to 12 carbon atoms, alkoxy radical having 1 to 6 carbon
atoms, alkenyloxy radical having 2 to 6 carbon atoms, alkylthio
radical having 1 to 6 carbon atoms or alkenylthio radical having 2
to 6 carbon atoms; X.sup.1 is (.alpha.-OZ.sup.a, .beta.-H) or
(.alpha.-H, .beta.-OZ.sup.a), X.sup.3 is (.alpha.-OZ.sup.d,
.beta.-H), (.alpha.-H, .beta.-OZ.sup.d) or oxygen atom, each of
Z.sup.a and Z.sup.d, which may be the same or different, is a
hydrogen atom or a protective radical for a hydroxyl radical;
R.sup.1 is a hydrogen atom, alkyl radical having 1 to 9 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, cycloalkyl radical having 3 to 8 carbon
atoms, aralkyl radical having 7 to 10 carbon atoms, aryl radical
having 6 to 8 carbon atoms, alkoxy radical having 1 to 6 carbon
atoms, alkenyloxy radical having 2 to 6 carbon atoms, halogen atom,
substituted silyl radical represented by SiR.sup.9R.sup.10R.sup.11
or substituted stannyl radical represented by SnR
.sup.14R.sup.15R.sup.16 wherein R.sup.9, R.sup.10 and R.sup.11 are
independently selected from the group consisting of a hydrogen
atom, chlorine atom, fluorine atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, alkoxy radical having 1 to 6 carbon atoms,
alkenyloxy radical having 2 to 6 carbon atoms, phenyl radical,
tolyl radical, and benzyl radical, R.sup.14, R.sup.15 and R.sup.16
are independently selected from the group consisting of a hydrogen
atom, chlorine atom, alkyl radical having 1 to 6 carbon atoms,
alkenyl radical having 2 to 6 carbon atoms, alkynyl radical having
2 to 6 carbon atoms, cycloalkyl radical having 3 to 8 carbon atoms,
alkoxy radical having 1 to 6 carbon atoms, alkenyloxy radical
having 2 to 6 carbon atoms, phenyl radical, tolyl radical, and
benzyl radical; R.sup.3 is a hydrogen atom, alkyl radical having 1
to 6 carbon atoms, alkenyl radical having 2 to 6 carbon atoms,
alkynyl radical having 2 to 6 carbon atoms or cycloalkyl radical
having 3 to 8 carbon atoms; R.sup.5, R.sup.6, R.sup.7, and R.sup.8
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, cycloalkyl radical having 3 to 8 carbon atoms,
alkoxycarbonyl radical, and alkenyloxycarbonyl radical; X.sup.2 is
CR.sup.12.dbd.CR.sup.13, C.ident.C, phenylene radical, carbonyl
radical, oxygen atom or sulfur atom wherein R.sup.12 and R.sup.13
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms; p is an
integer of 0 or 1, each of n and q is an integer of 0 to 5; and
Z.sup.1 is a hydrogen atom, COOR.sup.y, CN, OR, OCOR.sup.z,
CONR.sup.bR.sup.c or NR.sup.dR.sup.e wherein R.sup.y and R.sup.z
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms, R.sup.b
and R.sup.c are independently selected from the group consisting of
a hydrogen atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, and cycloalkyl radical having 3 to 8 carbon atoms,
R.sup.d and R.sup.e are independently selected from the group
consisting of a hydrogen atom, benzyl radical, phenyl radical,
alkyl radical having 1 to 6 carbon atoms, alkenyl radical having 2
to 6 carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms.
7. A method for preparing a substituted cyclopentene derivative of
the formula (VII): 80 wherein R, X.sup.1, X.sup.3, R.sup.1,
R.sup.3, R.sup.5, R.sup.6, R.sup.7, R.sup.8, X.sup.2, n, p, q, and
Z.sup.1 are as defined below, said method characterized by
comprising the step of oxidizing with an oxidizing agent such as
peroxides a substituted cyclopentene derivative of the formula
(VI): 81 wherein R is a hydrogen atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, aralkyl radical having 7 to 19 carbon atoms, aryl
radical having 6 to 12 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms,
alkylthio radical having 1 to 6 carbon atoms or alkenylthio radical
having 2 to 6 carbon atoms; X.sup.1 is (.alpha.-OZ.sup.a, .beta.-H)
or (.alpha.-H, .beta.-OZ.sup.a) , X.sup.3 is (.alpha.-OZ.sup.d,
.beta.-H), (.alpha.-H, .beta.-OZ.sup.d) or oxygen atom, each of
Z.sup.a and Z.sup.d, which may be the same or different, is a
hydrogen atom or a protective radical for a hydroxyl radical;
R.sup.1 is a hydrogen atom, alkyl radical having 1 to 9 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, cycloalkyl radical having 3 to 8 carbon
atoms, aralkyl radical having 7 to 10 carbon atoms, aryl radical
having 6 to 8 carbon atoms, alkoxy radical having 1 to 6 carbon
atoms, alkenyloxy radical having 2 to 6 carbon atoms, halogen atom,
substituted silyl radical represented by SiR.sup.9R.sup.10R.sup.11
or substituted stannyl radical represented by
SnR.sup.14R.sup.15R.sup.16 wherein R.sup.9, R.sup.10 and R.sup.11
are independently selected from the group consisting of a hydrogen
atom, chlorine atom, fluorine atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, alkoxy radical having 1 to 6 carbon atoms,
alkenyloxy radical having 2 to 6 carbon atoms, phenyl radical,
tolyl radical, and benzyl radical, R.sup.14, R.sup.15 and R.sup.16
are independently selected from the group consisting of a hydrogen
atom, chlorine atom, alkyl radical having 1 to 6 carbon atoms,
alkenyl radical having 2 to 6 carbon atoms, alkynyl radical having
2 to 6 carbon atoms, cycloalkyl radical having 3 to 8 carbon atoms,
alkoxy radical having 1 to 6 carbon atoms, alkenyloxy radical
having 2 to 6 carbon atoms, phenyl radical, tolyl radical, and
benzyl radical; R.sup.3 is a hydrogen atom, alkyl radical having 1
to 6 carbon atoms, alkenyl radical having 2 to 6 carbon atoms,
alkynyl radical having 2 to 6 carbon atoms or cycloalkyl radical
having 3 to 8 carbon atoms; R.sup.5, R.sup.6, R.sup.7, and R.sup.8
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, cycloalkyl radical having 3 to 8 carbon atoms,
alkoxycarbonyl radical, and alkenyloxycarbonyl radical; X.sup.2 is
CR.sup.12.dbd.CR.sup.13, C.ident.C, phenylene radical, carbonyl
radical, oxygen atom or sulfur atom wherein R.sup.12 and R.sup.13
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms; p is an
integer of 0 or 1, each of n and q is an integer of 0 to 5; and
Z.sup.1 is a hydrogen atom, COOR.sup.y, CN, OH, OCOR.sup.z,
CONR.sup.bR.sup.c or NR.sup.dR.sup.e wherein R.sup.y and R.sup.z
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms, R.sup.b
and R.sup.c are independently selected from the group consisting of
a hydrogen atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, and cycloalkyl radical having 3 to 8 carbon atoms,
R.sup.d and R.sup.e are independently selected from the group
consisting of a hydrogen atom, benzyl radical, phenyl radical,
alkyl radical having 1 to 6 carbon atoms, alkenyl radical having 2
to 6 carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms.
8. A method for preparing a substituted cyclopentene derivative of
the formula (IX): 82 wherein R, X.sup.1, X.sup.3, R.sup.3, R.sup.5,
R.sup.6, R.sup.7, R.sup.8, X.sup.2, n, p, q, and Z.sup.1 are as
defined below, said method characterized by comprising the step of
subjecting to acidolysis a substituted cyclopentene derivative of
the formula (VIII): 83 wherein R is a hydrogen atom, alkyl radical
having 1 to 6 carbon atoms, alkenyl radical having 2 to 6 carbon
atoms, alkynyl radical having 2 to 6 carbon atoms, cycloalkyl
radical having 3 to 8 carbon atoms, aralkyl radical having 7 to 19
carbon atoms, aryl radical having 6 to 12 carbon atoms, alkoxy
radical having 1 to 6 carbon atoms, alkenyloxy radical having 2 to
6 carbon atoms, alkylthio radical having 1 to 6 carbon atoms or
alkenylthio radical having 2 to 6 carbon atoms; X.sup.1 is
(.alpha.-OZ.sup.a, .beta.-H) or (.alpha.-H, .beta.-OZ.sup.a),
X.sup.3 is (.alpha.-OZ.sup.d, .beta.-H), (.alpha.-H,
.beta.-OZ.sup.d) or oxygen atom, each of Z.sup.a and Z.sup.d, which
may be the same or different, is a hydrogen atom or a protective
radical for a hydroxyl radical; R.sup.9, R.sup.10 and R.sup.11 are
independently selected from the group consisting of a hydrogen
atom, chlorine atom, fluorine atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, alkoxy radical having 1 to 6 carbon atoms,
alkenyloxy radical having 2 to 6 carbon atoms, phenyl radical,
tolyl radical, and benzyl radical; R.sup.5, R.sup.6, R.sup.7, and
R.sup.8 are independently selected from the group consisting of a
hydrogen atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, cycloalkyl radical having 3 to 8 carbon atoms,
alkoxycarbonyl radical, and alkenyloxycarbonyl radical; X.sup.2 is
CR.sup.12.dbd.CR.sup.13, C.ident.C, phenylene radical, carbonyl
radical, oxygen atom or sulfur atom wherein R.sup.12 and R.sup.13
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms; p is an
integer of 0 or 1, each of n and q is an integer of 0 to 5; and
Z.sup.1 is a hydrogen atom, COOR.sup.y, CN, OH, OCOR.sup.z,
CONR.sup.bR.sup.c or NR.sup.dR.sup.e wherein R.sup.y and R.sup.z
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms, R.sup.b
and R.sup.c are independently selected from the group consisting of
a hydrogen atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, and cycloalkyl radical having 3 to 8 carbon atoms,
R.sup.d and R.sup.e are independently selected from the group
consisting of a hydrogen atom, benzyl radical, phenyl radical,
alkyl radical having 1 to 6 carbon atoms, alkenyl radical having 2
to 6 carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms.
Description
TECHNICAL FIELD
[0001] This invention relates to substituted cyclopentene
derivatives and a method for preparing the same and more
particularly, to novel intermediates useful for the production of
prostaglandins (to be abbreviated as PG, hereinafter) useful as
various drugs, especially PGE.sub.2 and 6-keto-PGE.sub.1.
BACKGROUND ART
[0002] Since PGs exhibit various important physiological actions in
minor amounts, active research works have been made thereon for the
intended application to drugs. With respect to the extension of PG
analogues, it has been attempted in various ways to extend .alpha.
and .omega.-chains attached to the five-membered ring moiety. One
method capable of free choice of .alpha. and .omega.-chains and
efficient introduction is a two-component connecting method. More
particularly, direct synthesis is possible by 1,4-addition of a
zinc reagent of .alpha.-chain to an enone as shown by Scheme 1 (see
H. Tsujiyama, N. Ono, S. Okamoto, F. Sato, Tetrahedron Lett., 31,
4481 (1990)). 2
[0003] In the synthesis of an intermediate having a double bond in
its .alpha.-chain, however, it is synthesized by introducing an
.alpha.-chain into an enone using a vinyl lithium reagent and then
effecting functional group conversion as shown by Scheme 2. 3
[0004] The reason is as follows. It is impossible to form an
organic zinc reagent of an .alpha.-chain because reaction
conditions are severe and the stereo-chemistry of olefin is not
maintained. An .alpha.-chain is synthesized as an alcohol-protected
one because a lithium reagent having an ester group cannot be
synthesized. Many stages are thus necessary (see S. Okamoto, Y.
Kobayashi, H. Kato, K. Hori, T. Takahashi, J. Tsuji, F. Sato, J.
Org. Chem., 53, 5590 (1988)).
[0005] Also the route developed by E. J. Corey et al. (Scheme 3)
entails much decomposition and hence, low yields since Jones
oxidation under severe conditions is utilized. It is industrially
inadequate since a heavy metal (Cr) is used (see YAMAMOTO Shozo et
al., "Prostaglandins and Related Physiologically Active Compounds",
Kodansha, 1981). 4
[0006] Further, a silyl substituted derivative of formula (VIII)
which can be readily synthesized according to the present invention
as will be described later is useful in the synthesis of a
6-keto-prostaglandin which now draws attention as a ulcer drug. In
the past, an intermediate of this 6-keto-PG has been synthesized
through the following route. This technique, however, is not
satisfactory as a practical production process since only a racemic
modification is obtained and further optical resolution is needed
to obtain an optically active substance (see M. Brawner Floyd,
Synthetic Communications, 4 (6), 317-323 (1974)). 5
DISCLOSURE OF THE INVENTION
[0007] Therefore, an object of the present invention is to provide
a substituted cyclopentene derivative which is an intermediate for
producing PGE.sub.2, 6-keto-PGE.sub.1 and analogues in a more
advantageous manner and a method for preparing the same.
[0008] Making extensive investigations for attaining the above
object, the inventor has found that a novel halogenated substituted
cyclopentene derivative of formula (I) can be obtained by reacting
a compound of formula (II) with a halide of formula (III) or a
hydrate thereof in the presence or absence of a Lewis acid as shown
below by reaction scheme A; that a novel substituted cyclopentene
derivative of formula (V) can be obtained by reacting this novel
halogenated substituted cyclopentene derivative of formula (I) with
a novel compound of formula (IV) as shown below by reaction scheme
B; that a novel epoxy radical-containing substituted cyclopentene
derivative of formula (VII) is obtained by oxidizing a compound of
formula (VI) embraced in the novel substituted cyclopentene
derivative of formula (V) using an oxidizing agent such as
peroxides as shown below by reaction scheme C; that a substituted
cyclopentene derivative of formula (IX) can be obtained by
acidolysis of a compound of formula (VIII) which is a substituted
cyclopentene derivative of formula (VII) wherein R.sup.1 is a
substituted silyl radical as shown below by reaction scheme D; and
that PGs can be advantageously prepared from these substituted
cyclopentene derivatives. The present invention is predicated on
these findings. 6 7 8 9
[0009] More particularly, among PG synthesis methods, a method
represented by "Scheme 5" and known as a two-component method has
the advantages of easy reaction control due to the use of an
intermediate having an .alpha.-chain and more versatility of
.omega.-chain introduction. The present invention enables synthesis
of the following compounds (8b), (10d), etc. in accordance with
this method and effective preparation of PGE.sub.2 analogues or
6-keto-PGE.sub.1 analogues from these compounds as shown by "Scheme
6" and "Scheme 7." 10 11 12
[0010] In fact, synthesis of PGs themselves and intermediates (8b),
(11d), (13e), (16d), and (10c) is completed as will be shown in
Examples and Reference Examples later, with which the invention is
acknowledged useful. 13
[0011] Accordingly, the present invention provides (1) to (8) as
described below.
[0012] (1) A halogenated substituted cyclopentene derivative of the
formula (I): 14
[0013] wherein R is a hydrogen atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, aralkyl radical having 7 to 19 carbon atoms, aryl
radical having 6 to 12 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms,
alkylthio radical having 1 to 6 carbon atoms or alkenylthio radical
having 2 to 6 carbon atoms; X.sup.1 is (.alpha.-OZ.sup.a, .beta.-H)
or (.alpha.-H, .beta.-OZ.sup.a), X.sup.3 is (.alpha.-OZ.sup.d,
.beta.-H), (.alpha.-H, .beta.-OZ.sup.d), or oxygen atom, each of
Z.sup.a and Z.sup.d, which may be the same or different, is a
hydrogen atom or a protective radical for a hydroxyl radical; and W
is a halogen atom.
[0014] (2) A method for preparing a halogenated substituted
cyclopentene derivative of the formula (I): 15
[0015] wherein R, X.sup.1, X.sup.3, and W are as defined below,
[0016] said method comprising the step of reacting a substituted
cyclopentane derivative of the formula (II): 16
[0017] wherein R is a hydrogen atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, aralkyl radical having 7 to 19 carbon atoms, aryl
radical having 6 to 12 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms,
alkylthio radical having 1 to 6 carbon atoms or alkenylthio radical
having 2 to 6 carbon atoms; X.sup.1 is (.alpha.-OZ.sup.a, .beta.-H)
or (.alpha.-H, .beta.-OZ.sup.a), X.sup.3 is (.alpha.-OZ.sup.d,
.beta.-H), (.alpha.-H, .beta.OZ.sup.d) or oxygen atom, Y is
(.alpha.-OZ.sup.c, .beta.-H) or (.alpha.-H, .beta.OZ.sup.c), and
each of Z.sup.a, Z.sup.c and Z.sup.d, which may be the same or
different, is a hydrogen atom or a protective radical for a
hydroxyl radical, with a halide of the formula (III):
M.sup.1W.sub.h (III)
[0018] wherein M.sup.1 is a metal atom selected from the group
consisting of an alkali metal, alkaline earth metal, first
transition metal, Al, Zr, and Ce, or quaternary ammonium, W is a
halogen atom, and h representative of the valence of said metal or
quaternary ammonium is an integer of 1 to 4, or a hydrate thereof
in the presence or absence of a Lewis acid.
[0019] (3) A method for preparing a substituted cyclopentene
derivative of the formula (V): 17
[0020] wherein R, X.sup.1, X.sup.3, U, R.sup.5, R.sup.6, R.sup.7,
R.sup.8, X.sup.2, m, n, p, q, and Z.sup.1 are as defined below,
[0021] said method characterized by comprising the step of reacting
a halogenated substituted cyclopentene derivative of the formula
(I): 18
[0022] wherein R is a hydrogen atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, aralkyl radical having 7 to 19 carbon atoms, aryl
radical having 6 to 12 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms,
alkylthio radical having 1 to 6 carbon atoms or alkenylthio radical
having 2 to 6 carbon atoms; X.sup.1 is (.alpha.-OZ.sup.a, .beta.-H)
or (.alpha.-H, .beta.-OZ.sup.a), X.sup.3 is (.alpha.-OZ.sup.d,
.beta.-H), (.alpha.-H, .beta.-OZ.sup.d) or oxygen atom, each of
Z.sup.a and Z.sup.d, which may be the same or different, is a
hydrogen atom or a protective radical for a hydroxyl radical; and W
is a halogen atom with a compound of the formula (IV): 19
[0023] wherein M.sup.2 is a substituted borane radical, substituted
aluminum radical, substituted zirconium radical or substituted
stannyl radical each having a hydrogen atom, alkyl radical having 1
to 9 carbon atoms, cycloalkyl radical having 3 to 12 carbon atoms,
aralkyl radical having 7 to 10 carbon atoms, aryl radical having 6
to 8 carbon atoms, alkoxy radical having 1 to 6 carbon atoms,
dialkoxy radical having 2 to 12 carbon atoms, alkenyloxy radical
having 2 to 6 carbon atoms, substituted phenoxy radical, a
cyclopentadienyl radical or halogen atom substituent;
[0024] U is a radical selected from the group consisting of
CR.sup.1R.sup.2CR.sup.3R.sup.4, CR.sup.1.dbd.CR.sup.3, C.ident.C,
and phenylene wherein R.sup.1 is a hydrogen atom, alkyl radical
having 1 to 9 carbon atoms, alkenyl radical having 2 to 6 carbon
atoms, alkynyl radical having 2 to 6 carbon atoms, cycloalkyl
radical having 3 to 8 carbon atoms, aralkyl radical having 7 to 10
carbon atoms, aryl radical having 6 to 8 carbon atoms, alkoxy
radical having 1 to 6 carbon atoms, alkenyloxy radical having 2 to
6 carbon atoms, halogen atom, substituted silyl radical represented
by SiR.sup.9R.sup.10R.sup.11 or substituted stannyl radical
represented by SnR.sup.14R.sup.15R.sup.16 wherein R.sup.9, R.sup.10
and R.sup.11 are independently selected from the group consisting
of a hydrogen atom, chlorine atom, fluorine atom, alkyl radical
having 1 to 6 carbon atoms, alkenyl radical having 2 to 6 carbon
atoms, alkynyl radical having 2 to 6 carbon atoms, cycloalkyl
radical having 3 to 8 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms, phenyl
radical, tolyl radical, and benzyl radical, R.sup.14, R.sup.15 and
R.sup.16 are independently selected from the group consisting of a
hydrogen atom, chlorine atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, cycloalkyl radical having 3 to 8 carbon
atoms, alkoxy radical having 1 to 6 carbon atoms, alkenyloxy
radical having 2 to 6 carbon atoms, phenyl radical, tolyl radical,
and benzyl radical; R.sup.2, R.sup.3, and R.sup.4 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms; m is an integer of 0
to 6;
[0025] R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms,
cycloalkyl radical having 3 to 8 carbon atoms, alkoxycarbonyl
radical, and alkenyloxycarbonyl radical;
[0026] X.sup.2 is CR.sup.12.dbd.CR.sup.13, C.ident.C, phenylene
radical, carbonyl radical, oxygen atom or sulfur atom wherein
R.sup.12 and R.sup.13 are independently selected from the group
consisting of a hydrogen atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, and cycloalkyl radical having 3 to 8
carbon atoms; p is an integer of 0 or 1, each of n and q is an
integer of 0 to 5; and
[0027] Z.sup.1 is a hydrogen atom, COOR.sup.y, CN, OH, OCOR.sup.z,
CONR.sup.bR.sup.c or NR.sup.dR.sup.e wherein R.sup.y and R.sup.z
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms, R.sup.b
and R.sup.c are independently selected from the group consisting of
a hydrogen atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, and cycloalkyl radical having 3 to 8 carbon atoms,
R.sup.d and R.sup.e are independently selected from the group
consisting of a hydrogen atom, benzyl radical, phenyl radical,
alkyl radical having 1 to 6 carbon atoms, alkenyl radical having 2
to 6 carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms, in the presence or
absence of a metal catalyst.
[0028] (4) A compound of the formula (IV): 20
[0029] wherein M.sup.2 is a substituted borane radical, substituted
aluminum radical, substituted zirconium radical or substituted
stannyl radical each having a hydrogen atom, alkyl radical having 1
to 9 carbon atoms, cycloalkyl radical having 3 to 12 carbon atoms,
aralkyl radical having 7 to 10 carbon atoms, aryl radical having 6
to 8 carbon atoms, alkoxy radical having 1 to 6 carbon atoms,
dialkoxy radical having 2 to 12 carbon atoms, alkenyloxy radical
having 2 to 6 carbon atoms, substituted phenoxy radical, a
cyclopentadienyl radical or halogen atom substituent;
[0030] U is a radical selected from the group consisting of
CR.sup.1R.sup.2CR.sup.3R.sup.4, CR.sup.1.dbd.CR.sup.3, C.ident.C,
and phenylene wherein R.sup.1 is a hydrogen atom, alkyl radical
having 1 to 9 carbon atoms, alkenyl radical having 2 to 6 carbon
atoms, alkynyl radical having 2 to 6 carbon atoms, cycloalkyl
radical having 3 to 8 carbon atoms, aralkyl radical having 7 to 10
carbon atoms, aryl radical having 6 to 8 carbon atoms, alkoxy
radical having 1 to 6 carbon atoms, halogen atom, substituted silyl
radical represented by SiR.sup.9R.sup.10R.sup.11 or substituted
stannyl radical represented by SnR.sup.14R.sup.15R.sup.16 wherein
R.sup.9, R.sup.10 and R.sup.11 are independently selected from the
group consisting of a hydrogen atom, chlorine atom, fluorine atom,
alkyl radical having 1 to 6 carbon atoms, alkenyl radical having 2
to 6 carbon atoms, alkynyl radical having 2 to 6 carbon atoms,
cycloalkyl radical having 3 to 8 carbon atoms, alkoxy radical
having 1 to 6 carbon atoms, alkenyloxy radical having 2 to 6 carbon
atoms, phenyl radical, tolyl radical, and benzyl radical, R.sup.14,
R.sup.15 and R.sup.16 are independently selected from the group
consisting of a hydrogen atom, chlorine atom, alkyl radical having
1 to 6 carbon atoms, alkenyl radical having 2 to 6 carbon atoms,
alkynyl radical having 2 to 6 carbon atoms, cycloalkyl radical
having 3 to 8 carbon atoms, alkoxy radical having 1 to 6 carbon
atoms, alkenyloxy radical having 2 to 6 carbon atoms, phenyl
radical, tolyl radical, and benzyl radical; R.sup.2, R.sup.3, and
R.sup.4 are independently selected from the group consisting of a
hydrogen atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, and cycloalkyl radical having 3 to 8 carbon atoms; m
is an integer of 0 to 6;
[0031] R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms,
cycloalkyl radical having 3 to 8 carbon atoms, alkoxycarbonyl
radical, and alkenyloxycarbonyl radical;
[0032] X.sup.2 is CR.sup.12.dbd.CR.sup.13, C.ident.C , phenylene
radical, carbonyl radical, oxygen atom or sulfur atom wherein
R.sup.12 and R.sup.13 are independently selected from the group
consisting of a hydrogen atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, and cycloalkyl radical having 3 to 8
carbon atoms; p is an integer of 0 or 1, each of n and q is an
integer of 0 to 5; and
[0033] Z.sup.1 is a hydrogen atom, COOR.sup.y, CN, OH, OCOR.sup.z,
CONR.sup.bR.sup.c or NR.sup.dR.sup.e wherein R.sup.y and R.sup.z
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms, R.sup.b
and R.sup.c are independently selected from the group consisting of
a hydrogen atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, and cycloalkyl radical having 3 to 8 carbon atoms,
R.sup.d and R.sup.e are independently selected from the group
consisting of a hydrogen atom, benzyl radical, phenyl radical,
alkyl radical having 1 to 6 carbon atoms, alkenyl radical having 2
to 6 carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms.
[0034] (5) A compound of the formula (V): 21
[0035] wherein R is a hydrogen atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, aralkyl radical having 7 to 19 carbon atoms, aryl
radical having 6 to 12 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms,
alkylthio radical having 1 to 6 carbon atoms or alkenylthio radical
having 2 to 6 carbon atoms;
[0036] X.sup.1 is (.alpha.-OZ.sup.a, .beta.-H) or (.alpha.-H,
.beta.-OZ.sup.a), X.sup.3 is (.alpha.-OZ.sup.d, .beta.-H),
(.alpha.-H, .beta.-OZ.sup.d) or oxygen atom, each of Z.sup.a and
Z.sup.d, which may be the same or different, is a hydrogen atom or
a protective radical for a hydroxyl radical;
[0037] U is a radical selected from the group consisting of
CR.sup.1R.sup.2CR.sup.3R.sup.4, CR.sup.1.dbd.CR.sup.3, C.ident.C,
and phenylene wherein R.sup.1 is a hydrogen atom, alkyl radical
having 1 to 9 carbon atoms, alkenyl radical having 2 to 6 carbon
atoms, alkynyl radical having 2 to 6 carbon atoms, cycloalkyl
radical having 3 to 8 carbon atoms, aralkyl radical having 7 to 10
carbon atoms, aryl radical having 5 to 8 carbon atoms, alkoxy
radical having 1 to 6 carbon atoms, alkenyloxy radical having 2 to
6 carbon atoms, halogen atom, substituted silyl radical represented
by SiR.sup.9R.sup.10R.sup.11 or substituted stannyl radical
represented by SnR.sup.14R.sup.15R.sup.16 wherein R.sup.9, R.sup.10
and R.sup.11 are independently selected from the group consisting
of a hydrogen atom, chlorine atom, fluorine atom, alkyl radical
having 1 to 6 carbon atoms, alkenyl radical having 2 to 6 carbon
atoms, alkynyl radical having 2 to 6 carbon atoms, cycloalkyl
radical having 3 to 8 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms, phenyl
radical, tolyl radical, and benzyl radical, R .sup.14, R.sup.15 and
R.sup.16 are independently selected from the group consisting of a
hydrogen atom, chlorine atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, cycloalkyl radical having 3 to 8 carbon
atoms, alkoxy radical having 1 to 6 carbon atoms, alkenyloxy
radical having 2 to 6 carbon atoms, phenyl radical, tolyl radical,
and benzyl radical; R.sup.2, R.sup.3, and R.sup.4 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms; m is an integer of 0
to 6;
[0038] R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms,
cycloalkyl radical having 3 to 8 carbon atoms, alkoxycarbonyl
radical, and alkenyloxycarbonyl radical;
[0039] X.sup.2 is CR.sup.12.dbd.CR.sup.13, C.ident.C, phenylene
radical, carbonyl radical, oxygen atom or sulfur atom wherein
R.sup.12 and R.sup.13 are independently selected from the group
consisting of a hydrogen atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, and cycloalkyl radical having 3 to 8
carbon atoms; p is an integer of 0 or 1, each of n and q is an
integer of 0 to 5; and
[0040] Z.sup.1 is a hydrogen atom, COOR.sup.y, CN, OH, OCOR.sup.z,
CONR.sup.bR.sup.c or NR.sup.dR.sup.e wherein R.sup.y and R.sup.z
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms, R.sup.b
and R.sup.c are independently selected from the group consisting of
a hydrogen atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, and cycloalkyl radical having 3 to 8 carbon atoms,
R.sup.d and R.sup.e are independently selected from the group
consisting of a hydrogen atom, benzyl radical, phenyl radical,
alkyl radical having 1 to 6 carbon atoms, alkenyl radical having 2
to 6 carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms.
[0041] (6) A substituted cyclopentene derivative of the formula
(VII): 22
[0042] wherein R is a hydrogen atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, aralkyl radical having 7 to 19 carbon atoms, aryl
radical having 6 to 12 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms,
alkylthio radical having 1 to 6 carbon atoms or alkenylthio radical
having 2 to 6 carbon atoms;
[0043] X.sup.1 is (.alpha.-OZ.sup.a, .beta.-H) or (.alpha.-H,
.beta.-OZ.sup.a), X.sup.3 is (.alpha.-OZ.sup.d, .beta.-H),
(.alpha.-H, .beta.-OZ.sup.d) or oxygen atom, each of Z.sup.a and
Z.sup.d, which may be the same or different, is a hydrogen atom or
a protective radical for a hydroxyl radical;
[0044] R.sup.1 is a hydrogen atom, alkyl radical having 1 to 9
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, aralkyl radical having 7 to 10 carbon atoms, aryl
radical having 6 to 8 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms,
halogen atom, substituted silyl radical represented by SiR.sup.9R
.sup.10R.sup.11 or substituted stannyl radical represented by
SnR.sup.14R.sup.15R.sup.16 wherein R.sup.9, R.sup.10 and R.sup.11
are independently selected from the group consisting of a hydrogen
atom, chlorine atom, fluorine atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, alkoxy radical having 1 to 6 carbon atoms,
alkenyloxy radical having 2 to 6 carbon atoms, phenyl radical,
tolyl radical, and benzyl radical, R.sup.14, R.sup.15 and R.sup.16
are independently selected from the group consisting of a hydrogen
atom, chlorine atom, alkyl radical having 1 to 6 carbon atoms,
alkenyl radical having 2 to 6 carbon atoms, alkynyl radical having
2 to 6 carbon atoms, cycloalkyl radical having 3 to 8 carbon atoms,
alkoxy radical having 1 to 6 carbon atoms, alkenyloxy radical
having 2 to 6 carbon atoms, phenyl radical, tolyl radical, and
benzyl radical;
[0045] R.sup.3 is a hydrogen atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms or cycloalkyl radical having 3
to 8 carbon atoms;
[0046] R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms,
cycloalkyl radical having 3 to 8 carbon atoms, alkoxycarbonyl
radical, and alkenyloxycarbonyl radical;
[0047] X.sup.2 is CR.sup.12.dbd.CR.sup.13, C.ident.C, phenylene
radical, carbonyl radical, oxygen atom or sulfur atom wherein
R.sup.12 and R.sup.13 are independently selected from the group
consisting of a hydrogen atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, and cycloalkyl radical having 3 to 8
carbon atoms; p is an integer of 0 or 1, each of n and q is an
integer of 0 to 5; and
[0048] Z.sup.1 is a hydrogen atom, COOR.sup.y, CN, OH, OCOR.sup.z,
CONR.sup.bR.sup.c or NR.sup.dR.sup.e wherein R.sup.y and R.sup.z
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms, R.sup.b
and R.sup.c are independently selected from the group consisting of
a hydrogen atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, and cycloalkyl radical having 3 to 8 carbon atoms,
R.sup.d and R.sup.e are independently selected from the group
consisting of a hydrogen atom, benzyl radical, phenyl radical,
alkyl radical having 1 to 6 carbon atoms, alkenyl radical having 2
to 6 carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms.
[0049] (7) A method for preparing a substituted cyclopentene
derivative of the formula (VII): 23
[0050] wherein R, X.sup.1, X.sup.3, R.sup.1, R.sup.3, R.sup.5,
R.sup.6, R.sup.7, R.sup.8, X.sup.2, n, p, q, and Z.sup.1 are as
defined below,
[0051] said method characterized by comprising the step of
oxidizing with an oxidizing agent such as peroxides a substituted
cyclopentene derivative of the formula (VI): 24
[0052] wherein R is a hydrogen atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, aralkyl radical having 7 to 19 carbon atoms, aryl
radical having 6 to 12 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms,
alkylthio radical having 1 to 6 carbon atoms or alkenylthio radical
having 2 to 6 carbon atoms;
[0053] X.sup.1 is (.alpha.-OZ.sup.a, .beta.-H) or (.alpha.-H,
.beta.-OZ.sup.a), X.sup.3 is (.alpha.-OZ.sup.d, .beta.-H),
(.alpha.-H, .beta.-OZ.sup.d) or oxygen atom, each of Z.sup.a and
Z.sup.d, which may be the same or different, is a hydrogen atom or
a protective radical for a hydroxyl radical;
[0054] R.sup.1 is a hydrogen atom, alkyl radical having 1 to 9
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, aralkyl radical having 7 to 10 carbon atoms, aryl
radical having 6 to 8 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms,
halogen atom, substituted silyl radical represented by
SiR.sup.9R.sup.10R.sup.11 or substituted stannyl radical
represented by SnR.sup.14R.sup.15R.sup.16 wherein R.sup.9, R.sup.10
and R.sup.11 are independently selected from the group consisting
of a hydrogen atom, chlorine atom, fluorine atom, alkyl radical
having 1 to 6 carbon atoms, alkenyl radical having 2 to 6 carbon
atoms, alkynyl radical having 2 to 6 carbon atoms, cycloalkyl
radical having 3 to 8 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms, phenyl
radical, tolyl radical, and benzyl radical, R.sup.14, R.sup.15 and
R.sup.16 are independently selected from the group consisting of a
hydrogen atom, chlorine atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, cycloalkyl radical having 3 to 8 carbon
atoms, alkoxy radical having 1 to 6 carbon atoms, alkenyloxy
radical having 2 to 6 carbon atoms, phenyl radical, tolyl radical,
and benzyl radical;
[0055] R.sup.3 is a hydrogen atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms or cycloalkyl radical having 3
to 8 carbon atoms;
[0056] R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms,
cycloalkyl radical having 3 to 8 carbon atoms, alkoxycarbonyl
radical, and alkenyloxycarbonyl radical;
[0057] X.sup.2 is CR.sup.12.dbd.CR.sup.13, C.ident.C, phenylene
radical, carbonyl radical, oxygen atom or sulfur atom wherein
R.sup.12 and R.sup.13 are independently selected from the group
consisting of a hydrogen atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, and cycloalkyl radical having 3 to 8
carbon atoms; p is an integer of 0 or 1, each of n and q is an
integer of 0 to 5; and
[0058] Z.sup.1 is a hydrogen atom, COOR.sup.y, CN, OH, OCOR.sup.z,
CONR.sup.bR.sup.c or NR.sup.dR.sup.e wherein R.sup.y and R.sup.z
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms, R.sup.b
and R.sup.c are independently selected from the group consisting of
a hydrogen atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, and cycloalkyl radical having 3 to 8 carbon atoms,
R.sup.d and R.sup.e are independently selected from the group
consisting of a hydrogen atom, benzyl radical, phenyl radical,
alkyl radical having 1 to 6 carbon atoms, alkenyl radical having 2
to 6 carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms.
[0059] (8) A method for preparing a substituted cyclopentene
derivative of the formula (IX): 25
[0060] wherein R, X.sup.1, X.sup.3, R.sup.3, R.sup.5, R.sup.6,
R.sup.7, R.sup.8, X.sup.2, n, p, q, and Z.sup.1 are as defined
below,
[0061] said method characterized by comprising the step of
subjecting to acidolysis a substituted cyclopentene derivative of
the formula (VIII): 26
[0062] wherein R is a hydrogen atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, aralkyl radical having 7 to 19 carbon atoms, aryl
radical having 6 to 12 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, alkenyloxy radical having 2 to 6 carbon atoms,
alkylthio radical having 1 to 6 carbon atoms or alkenylthio radical
having 2 to 6 carbon atoms;
[0063] X.sup.1 is (.alpha.-OZ.sup.a, .beta.-H) or (.alpha.-H,
.beta.-OZ.sup.a), X.sup.3 is (.alpha.-OZ.sup.d, .beta.-H),
(.alpha.-H, .beta.-OZ.sup.d) or oxygen atom, each of Z.sup.a and
Z.sup.d, which may be the same or different, is a hydrogen atom or
a protective radical for a hydroxyl radical;
[0064] R.sup.9, R.sup.10 and R.sup.11 are independently selected
from the group consisting of a hydrogen atom, chlorine atom,
fluorine atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, cycloalkyl radical having 3 to 8 carbon atoms, alkoxy
radical having 1 to 6 carbon atoms, alkenyloxy radical having 2 to
6 carbon atoms, phenyl radical, tolyl radical, and benzyl
radical;
[0065] R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms,
cycloalkyl radical having 3 to 8 carbon atoms, alkoxycarbonyl
radical, and alkenyloxycarbonyl radical;
[0066] X.sup.2 is CR.sup.12.dbd.CR.sup.13, C.ident.C, phenylene
radical, carbonyl radical, oxygen atom or sulfur atom wherein
R.sup.12 and R.sup.13 are independently selected from the group
consisting of a hydrogen atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, and cycloalkyl radical having 3 to 8
carbon atoms; p is an integer of 0 or 1, each of n and q is an
integer of 0 to 5; and
[0067] Z.sup.1 is a hydrogen atom, COOR.sup.y, CN, OH, OCOR.sup.z,
CONR.sup.bR.sup.c or NR.sup.dR.sup.e wherein R.sup.y and R.sup.z
are independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms, R.sup.b
and R.sup.c are independently selected from the group consisting of
a hydrogen atom, alkyl radical having 1 to 6 carbon atoms, alkenyl
radical having 2 to 6 carbon atoms, alkynyl radical having 2 to 6
carbon atoms, and cycloalkyl radical having 3 to 8 carbon atoms,
R.sup.d and R.sup.e are independently selected from the group
consisting of a hydrogen atom, benzyl radical, phenyl radical,
alkyl radical having 1 to 6 carbon atoms, alkenyl radical having 2
to 6 carbon atoms, alkynyl radical having 2 to 6 carbon atoms, and
cycloalkyl radical having 3 to 8 carbon atoms.
BEST MODE FOR CARRYING OUT THE INVENTION
[0068] Now the present invention is described in further detail.
The invention provides compounds of the following formulae (I),
(IV), (V), and (VII). 27 28 29 30
[0069] In the formulae, R is a hydrogen atom, alkyl radical having
1 to 6 carbon atoms, alkenyl radical having 2 to 6 carbon atoms,
alkynyl radical having 2 to 6 carbon atoms, cycloalkyl radical
having 3 to 8 carbon atoms, aralkyl radical having 7 to 19 carbon
atoms, aryl radical having 6 to 12 carbon atoms, alkoxy radical
having 1 to 6 carbon atoms, alkenyloxy radical having 2 to 6 carbon
atoms, alkylthio radical having 1 to 6 carbon atoms or alkenylthio
radical having 2 to 6 carbon atoms. Specifically stated, the alkyl
radical includes methyl, ethyl, propyl, isopropyl, butyl, isobutyl,
t-butyl, pentyl, hexyl, 1-methylpentyl, and 2-methylpentyl. The
alkenyl radical includes vinyl, propenyl, isopropenyl, allyl,
1-butenyl, 2-butenyl, 1-pentenyl, 2-hexenyl, 3-methyl-2-butenyl,
and 3-methyl-2-pentenyl. The alkynyl radical includes ethynyl,
1-propynyl, 1-butynyl, and 1-methyl-3-pentynyl. The cycloalkyl
radical includes cyclopropyl, cyclobutyl, cyclopentyl,
4-methyl-cyclopentyl, cyclohexyl, cyclopropylmethyl,
cyclobutyl-methyl, and cyclopropylethyl. The aralkyl radical
include benzyl, naphthylmethyl, phenethyl, 1-naphthylethyl and
triphenylmethyl which may have a substituent. The aryl radical
includes phenyl and substituted phenyl radicals, with exemplary
substituents including halogen atoms, trifluoromethyl radicals,
alkyl radicals having 1 to 6 carbon atoms (e.g., methyl, ethyl,
propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, and hexyl),
alkoxy radicals having 1 to 6 carbon atoms (e.g., methoxy, ethoxy,
propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy, cyclopropoxy,
ethylenedioxy, 1,2-diphenylethylenedioxy, and propylene-dioxy),
alkylthio radicals having 1 to 6 carbon atoms (e.g., methylthio,
ethylthio, propylthio, isopropylthio, butylthio, isobutylthio,
t-butyl, pentylthio, and hexylthio), alkenyloxy radicals having 2
to 6 carbon atoms (e.g., vinyloxy, propenyloxy, isopropenyloxy,
allyloxy, 1-butenyloxy, 2-butenyloxy, 1-pentenyloxy, 2-hexenyloxy,
3-methyl-2-butenyloxy, and 3-methyl-2-pentenyloxy), and alkenylthio
radicals having 2 to 6 carbon atoms (e.g., vinylthio, propenylthio,
isopropenylthio, allylthio, 1-butenylthio, 2-butenylthio,
1-pentenylthio, 2-hexenylthio, 3-methyl-2-butenylthio, and
3-methyl-2-pentenylthio) as well as a phenyl radical, phenoxy
radical, nitro radical, cyano radical, amino radical and allyl
radical. The alkoxy radical includes methoxy, ethoxy, propoxy,
isopropoxy, butoxy, isobutoxy, t-butoxy, and cyclopropoxy. The
alkylthio radical includes methylthio, ethylthio, propylthio,
isopropylthio, butylthio, isobutylthio, t-butylthio,
cyclopropylthio, pentylthio, hexylthio, and allylthio. The
alkenylthio radical includes propenylthio, isopropenylthic,
allylthio, 1-butenylthio, 2-butenylthio, 1-pentenylthio,
2-hexenylthio, 3-methyl-2-butenylthio, and
3-methyl-2-pentenylthio.
[0070] X.sup.1 is (.alpha.-OZ.sup.a, .beta.-H) or (.alpha.-H,
.beta.-OZ.sup.a), X.sup.3 is (.alpha.-OZ.sup.d, .beta.-H) or
(.alpha.-H, .beta.-OZ.sup.d) or oxygen atom, and Y is
(.alpha.-OZ.sup.c, .beta.-H) or (.alpha.-H, .beta.-OZ.sup.c)
wherein each of Z.sup.a, Z.sup.d and Z.sup.c is a hydrogen atom or
a protective radical for a hydroxyl radical while they may be the
same or different. The protective radical may be selected from
those radicals commonly used in the PG area, for example,
substituted silyl radicals (e.g., trimethylsilyl,
triisopropylsilyl, t-butyldimethylsilyl, and t-butyldiphenylsilyl),
alkoxyalkyl radicals (e.g., methoxymethyl and ethoxyethyl),
aralkyloxyalkyl radicals (e.g., benzyl-oxymethyl), alkyl radicals
(e.g., methyl, ethyl, propyl, isopropyl, and t-butyl), aralkyl
radicals (e.g., benzyl and trityl), acyl radicals (e.g., formyl,
acetyl and benzoyl), and a tetrahydropyranyl (THP) radical.
[0071] W is a halogen atom. The halogen atoms include fluorine,
chlorine, bromine, and iodine atoms.
[0072] M.sup.2 is a substituted borane radical, substituted
aluminum radical, substituted zirconium radical or substituted
stannyl radical each having a hydrogen atom, alkyl radical having 1
to 9 carbon atoms, cycloalkyl radical having 3 to 12 carbon atoms,
aralkyl radical having 7 to 10 carbon atoms, aryl radical having 6
to 8 carbon atoms, alkoxy radical having 1 to 6 carbon atoms,
dialkoxy radical having 2 to 12 carbon atoms, alkenyloxy radical
having 2 to 6 carbon atoms, substituted phenoxy radical, a
cyclopentadienyl radical or halogen atom substituent. Examples of
the alkyl, cycloalkyl, aralkyl, aryl, and alkoxy radicals are those
exemplified above. The substituted borane radical includes
dithiamylborane, dicyclohexylborane, bicyclo[3.3.1]nona-9-borane,
thexylborane, 2-methyl-2,4-pentadiolborane, and catecholborane. The
substituted aluminum radical includes diethylaluminum,
dimethylaluminum, and diisobutylaluminum. The substituted zirconium
radical includes chlorodicyclopentadienylzirconium. The substituted
stannyl radical includes trimethylstannyl, triethylstannyl, and
tributylstannyl. Preferred are dithiamylborane, dicyclohexylborane,
bicyclo[3.3.1]nona-9-borane, and tributylstannyl radicals.
[0073] U is CR.sup.1R.sup.2CR.sup.3R.sup.4, CR.sup.1.dbd.CR.sup.3,
C.ident.C or phenylene radical.
[0074] R.sup.1 is a hydrogen atom, alkyl radical having 1 to 9
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, cycloalkyl radical having 3 to
8 carbon atoms, aralkyl radical having 7 to 10 carbon atoms, aryl
radical having 6 to 8 carbon atoms, alkoxy radical having 1 to 6
carbon atoms, halogen atom, substituted silyl radical represented
by SiR.sup.9R.sup.10R.sup.11 or substituted stannyl radical
represented by SnR.sup.14R.sup.15R.sup.16.
[0075] Specifically stated, the alkyl radical includes methyl,
ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl,
1-methylpentyl, heptyl, octyl, 1-methylpentyl, 2-methylpentyl,
1-methylhexyl, 2-methylhexyl, 2,4-dimethyl-pentyl, 2-ethylpentyl,
2-methylheptyl, 2-ethylhexyl, and 2-propylpentyl.
[0076] The alkenyl radical includes vinyl, propenyl, isopropenyl,
allyl, 1-butenyl, 2-butenyl, 1-pentenyl, 2-hexenyl,
3-methyl-2-butenyl, and 3-methyl-2-pentenyl.
[0077] The alkynyl radical includes ethynyl, 1-propynyl, 1-butynyl,
and 1-methyl-3-pentynyl.
[0078] The cycloalkyl radical includes cyclopropyl, cyclobutyl,
cyclopentyl, 4-methylcyclopentyl, cyclohexyl, cyclopropylmethyl,
cyclobutylmethyl, and cyclopropylethyl.
[0079] The aralkyl radical include benzyl, naphthylmethyl,
phenethyl, 1-naphthylethyl and triphenylmethyl which may have a
substituent.
[0080] The aryl radical includes phenyl and substituted phenyl
radicals having a substituent, for example, halogen atoms,
trifluoromethyl radicals, alkyl radicals having 1 to 6 carbon atoms
(e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl,
pentyl, and hexyl), alkoxy radicals having 1 to 6 carbon atoms
(e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy,
t-butoxy, cyclopropoxy, ethylenedioxy, 1,2-diphenylethylenedioxy,
and propylenedioxy), alkylthio radicals having 1 to 6 carbon atoms
(e.g., methylthio, ethylthio, propylthio, isopropylthio, butylthio,
isobutylthio, t-butyl, pentylthio, and hexylthio), and the
aforementioned alkenylthio radicals as well as a phenyl radical,
phenoxy radical, nitro radical, cyano radical, amino radical and
allyl radical.
[0081] The alkoxy radical includes methoxy, ethoxy, propoxy,
isopropoxy, butoxy, isobutoxy, t-butoxy, and cyclopropoxy
[0082] The halogen atom includes fluorine, chlorine, bromine, and
iodine atoms.
[0083] R.sup.9, R.sup.10 and R.sup.11 in the substituted silyl
radical SiR.sup.9R.sup.10R.sup.11 are independently selected from
the group consisting of a hydrogen atom, chlorine atom, fluorine
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, cycloalkyl radical having 3 to 8 carbon atoms, alkenylthio
radical having 2 to 6 carbon atoms, and alkoxy radical having 1 to
6 carbon atoms. Specifically stated, the alkyl radical includes
methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl,
hexyl, 1-methylpentyl, 2-methylpentyl, and tetrahydropyranyl. The
alkenyl radical includes vinyl, propenyl, isopropenyl, allyl,
1-butenyl, 2-butenyl, 1-pentenyl, 2-hexenyl, 3-methyl-2-butenyl,
and 3-methyl-2-pentenyl. The alkynyl radical includes ethynyl,
1-propynyl, 1-butynyl, and 1-methyl-3-pentynyl. The cycloalkyl
radical include cyclopropyl, cyclobutyl, cyclopentyl,
4-methylcyclopentyl, cyclohexyl, cyclopropylmethyl,
cyclobutylmethyl, and cyclopropylethyl. The alkoxy radical includes
methoxy, ethoxy, propoxy, isopropoxy, butoxy, and t-butoxy. The
alkenyloxy radical includes vinyloxy, propenyloxy, isopropenyloxy,
allyloxy, 1-butenyloxy, 2-butenyloxy, 1-pentenyloxy, 2-hexenyloxy,
3-methyl-2-butenyloxy, and 3-methyl-2-pentenyloxy.
[0084] Examples of the substituted silyl radical include
trimethylsilyl, triethylsilyl, triisopropylsilyl,
t-butyldimethylsilyl, dimethylisopropylsilyl,
diethylisopropylsilyl, triphenylsilyl, tribenzylsilyl,
t-butyldiphenylsilyl, trichlorosilyl, methyldichlorosilyl,
dimethylchlorosilyl, dichloromethylsilyl, trifluorosilyl,
methyldifluorosilyl, dimethylfluorosilyl, triethoxysilyl,
ethyldimethoxysilyl, ethyldiethoxysilyl, ethyldiisopropoxysilyl,
diethylethoxysilyl, dimethylmethoxysilyl, dimethylethoxysilyl,
diethoxymethylsilyl, dimethylisopropoxysilyl, and
methyldiethoxysilyl. The preferred radical is trimethylsilyl.
[0085] R.sup.14, R.sup.15 and R.sup.16 in the substituted stannyl
radical SnR.sup.14R.sup.15R.sup.16 are independently selected from
the group consisting of a hydrogen atom, chlorine atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms,
cycloalkyl radical having 3 to 8 carbon atoms, and alkoxy radical
having 1 to 6 carbon atoms. Specifically stated, the alkyl radical
includes methyl, ethyl, propyl, isopropyl, butyl, isobutyl,
t-butyl, pentyl, hexyl, 1-methylpentyl, and 2-methylpentyl. The
alkenyl radical includes vinyl, propenyl, isopropenyl, allyl,
1-butenyl, 2-butenyl, 1-pentenyl, 2-hexenyl, 3-methyl-2-butenyl,
and 3-methyl-2-pentenyl. The alkynyl radical includes ethynyl,
1-propynyl, 1-butynyl, and 1-methyl-3-pentynyl. The cycloalkyl
radical include cyclopropyl, cyclobutyl, cyclopentyl,
4-methylcyclopentyl, cyclohexyl, cyclopropylmethyl,
cyclobutylmethyl, and cyclopropylethyl. The alkoxy radical includes
methoxy, ethoxy, propoxy, isopropoxy, butoxy, and t-butoxy. The
alkenyloxy radical includes vinyloxy, propenyloxy, isopropenyloxy,
allyloxy, 1-butenyloxy, 2-butenyloxy, 1-pentenyloxy, 2-hexenyloxy,
3-methyl-2-butenyloxy, and 3-methyl-2-pentenyloxy.
[0086] Examples of the substituted stannyl radical include
trimethylstannyl, tributylstannyl, and dibutylvinylstannyl. The
preferred radical is tributylstannyl.
[0087] R.sup.2, R.sup.3, and R.sup.4 are independently selected
from the group consisting of a hydrogen atom, alkyl radical having
1 to 6 carbon atoms, alkenyl radical having 2 to 6 carbon atoms,
alkynyl radical having 2 to 6 carbon atoms, and cycloalkyl radical
having 3 to 8 carbon atoms. Specifically stated, the alkyl radical
includes methyl, ethyl, propyl, isopropyl, butyl, isobutyl,
t-butyl, pentyl, hexyl, 1-methylpentyl, and 2-methylpentyl. The
alkenyl radical includes vinyl, propenyl, isopropenyl, allyl,
1-butenyl, 2-butenyl, 1-pentenyl, 2-hexenyl, 3-methyl-2-butenyl,
and 3-methyl-2-pentenyl. The alkynyl radical includes ethynyl,
1-propynyl, 1-butynyl, and 1-methyl-3-pentynyl. The cycloalkyl
radical includes cyclopropyl, cyclobutyl, cyclopentyl,
4-methylcyclopentyl, cyclohexyl, cyclopropylmethyl,
cyclobutylmethyl, and cyclopropylethyl.
[0088] Letter m is an integer of 0 to 6.
[0089] R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently
selected from the group consisting of a hydrogen atom, alkyl
radical having 1 to 6 carbon atoms, alkenyl radical having 2 to 6
carbon atoms, alkynyl radical having 2 to 6 carbon atoms,
cycloalkyl radical having 3 to 8 carbon atoms, alkoxycarbonyl
radical, and alkenyloxycarbonyl radical. Specifically stated, the
alkyl radical includes methyl, ethyl, propyl, isopropyl, butyl,
isobutyl, t-butyl, pentyl, hexyl, 1-methylpentyl, and
2-methylpentyl. The alkenyl radical includes vinyl, propenyl,
isopropenyl, allyl, 1-butenyl, 2-butenyl, 1-pentenyl, 2-hexenyl,
3-methyl-2-butenyl, and 3-methyl-2-pentenyl. The alkynyl radical
includes ethynyl, 1-propynyl, 1-butynyl, and 1-methyl-3-pentynyl.
The cycloalkyl radical includes cyclopropyl, cyclobutyl,
cyclopentyl, 4-methylcyclopentyl, cyclohexyl, cyclopropylmethyl,
cyclobutylmethyl, and cyclopropylethyl. The alkoxycarbonyl radical
includes methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
isopropoxycarbonyl, butoxycarbonyl and t-butoxycarbonyl. The
alkenyloxycarbonyl radical includes vinyloxy, propenyloxy,
isopropenyloxy, allyloxy, 1-butenyloxy, 2-butenyloxy,
1-pentenyloxy, 2-hexenyloxy, 3-methyl-2-butenyloxy, and
3-methyl-2-pentenyloxy.
[0090] X.sup.2 is CR.sup.12.dbd.CR.sup.13, C.ident.C, phenylene
radical, carbonyl radical, oxygen atom or sulfur atom wherein
R.sup.12 and R.sup.13 are independently selected from the group
consisting of a hydrogen atom, alkyl radical having 1 to 6 carbon
atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl radical
having 2 to 6 carbon atoms, and cycloalkyl radical having 3 to 8
carbon atoms.
[0091] Specifically stated, the alkyl radical includes methyl,
ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl,
1-methylpentyl, and 2-methylpentyl. The alkenyl radical includes
vinyl, propenyl, isopropenyl, allyl, 1-butenyl, 2-butenyl,
1-pentenyl, 2-hexenyl, 3-methyl-2-butenyl, and 3-methyl-2-pentenyl.
The alkynyl radical includes ethynyl, 1-propynyl, 1-butynyl, and
1-methyl-3-pentynyl. The cycloalkyl radical includes cyclopropyl,
cyclobutyl, cyclopentyl, 4-methylcyclopentyl, cyclohexyl,
cyclopropylmethyl, cyclobutylmethyl, and cyclopropylethyl.
[0092] The phenylene radical is selected from the group consisting
of 1,2-, 1,3- and 1,4-phenylene radicals which may be substituted
with substituents, for example, halogen atoms, trifluoromethyl,
alkyl radicals having 1 to 6 carbon atoms (e.g., methyl, ethyl,
propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl,
1-methylpentyl, and 2-methylpentyl), alkoxy radicals having 1 to 6
carbon atoms (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy,
isobutoxy, and t-butoxy, and cyclopropoxy), alkylthio radicals
having 1 to 6 carbon atoms (e.g., methylthio, ethylthio,
propylthio, isopropylthio, butylthio, isobutylthio, t-butyl,
pentylthio, and hexylthio), alkenylthio radicals as mentioned
above, phenyl, phenoxy, nitro, cyano, amino, and aryl radicals.
[0093] Letter p is an integer of 0 or 1 and each of n and q is an
integer of 0 to 5.
[0094] Z.sup.1 is a hydrogen atom, COOR.sup.y, CN, OH, OCOR.sup.z,
CONR.sup.bR.sup.c or NR.sup.dR.sup.e. R.sup.y and R.sup.z are
independently selected from the group consisting of a hydrogen
atom, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms.
Specifically stated, the alkyl radical includes methyl, ethyl,
propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl,
1-methylpentyl, and 2-methylpentyl. The alkenyl radical includes
vinyl, propenyl, isopropenyl, allyl, 1-butenyl, 2-butenyl,
1-pentenyl, 2-hexenyl, 3-methyl-2-butenyl, and 3-methyl-2-pentenyl.
The alkynyl radical includes ethynyl, 1-propynyl, 1-butynyl, and
1-methyl-3-pentynyl. The cycloalkyl radical includes cyclopropyl,
cyclobutyl, cyclopentyl, 4-methylcyclopentyl, cyclohexyl,
cyclopropylmethyl, cyclobutylmethyl, and cyclopropvlethyl.
[0095] R.sup.b and R.sup.c are independently selected from the
group consisting of a hydrogen atom, alkyl radical having 1 to 6
carbon atoms, alkenyl radical having 2 to 6 carbon atoms, alkynyl
radical having 2 to 6 carbon atoms, and cycloalkyl radical having 3
to 8 carbon atoms. Specifically stated, the alkyl radical includes
methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl,
hexyl, 1-methylpentyl, and 2-methylpentyl. The alkenyl radical
includes vinyl, propenyl, isopropenyl, allyl, 1-butenyl, 2-butenyl,
1-pentenyl, 2-hexenyl, 3-methyl-2-butenyl, and 3-methyl-2-pentenyl.
The alkynyl radical includes ethynyl, 1-propynyl, 1-butynyl, and
1-methyl-3-pentynyl. The cycloalkyl radical includes cyclopropyl,
cyclobutyl, cyclopentyl, 4-methylcyclopentyl, cyclohexyl,
cyclopropylmethyl, cyclobutylmethyl, and cyclopropylethyl. The
alkoxy radical includes methoxy, ethoxy, propoxy, isopropoxy,
butoxy, and t-butoxy.
[0096] R.sup.d and R.sup.e are independently selected from the
group consisting of a hydrogen atom, benzyl radical, phenyl
radical, alkyl radical having 1 to 6 carbon atoms, alkenyl radical
having 2 to 6 carbon atoms, alkynyl radical having 2 to 6 carbon
atoms, and cycloalkyl radical having 3 to 8 carbon atoms.
Specifically stated, the alkyl radical includes methyl, ethyl,
propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl,
1-methylpentyl, and 2-methylpentyl. The alkenyl radical includes
vinyl, propenyl, isopropenyl, allyl, 1-butenyl, 2-butenyl,
1-pentenyl, 2-hexenyl, 3-methyl-2-butenyl, and 3-methyl-2-pentenyl.
The alkynyl radical includes ethynyl, 1-propynyl, 1-butynyl, and
1-methyl-3-pentynyl. The cycloalkyl radical includes cyclopropyl,
cyclobutyl, cyclopentyl, 4-methylcyclopentyl, cyclohexyl,
cyclopropylmethyl, cyclobutylmethyl, and cyclopropylethyl. The
alkoxy radical includes methoxy, ethoxy, propoxy, isopropoxy,
butoxy, and t-butoxy.
[0097] In another aspect, the present invention provides
preparation methods according to the following reaction schemes A
to D. 31 32 33 34
[0098] In the formulae, M.sup.1 is a metal atom selected from the
group consisting of alkali metals, alkaline earth metals, first
transition metals, Al, Zr, and Ce, or quaternary ammonium. Examples
include lithium, sodium, potassium, magnesium, calcium, titanium,
zirconium, cerium, nickel, zinc, aluminum, tetrabutylammonium,
tetraethylammonium, benzyltrimethylammonium,
benzyltriethylammonium, trioctylmethylammonium. h which is
representative of the valence of the above-mentioned metal or
quaternary ammonium is an integer of 1 to 4. It is understood that
the remaining radicals are as previously defined.
[0099] In the above-mentioned reaction scheme A, the substituted
cyclopentane derivatives of formula (II) used as a starting
material in the present invention are known compounds when X.sup.3
is an oxygen atom, which can be synthesized by the method of JP-A
128/1990 or EP 0295880(A1) or the like. Those substituted
cyclopentane derivatives of formula (II) wherein X.sup.3 is
(.alpha.-OZ.sup.d, .beta.-H) or (.alpha.-H, .beta.-OZ.sup.d) can be
synthesized by reacting a substituted cyclopentene derivative
wherein X.sup.3 is an oxygen atom with a reducing agent and
optionally introducing a protective radical.
[0100] With regard to the reaction of a substituted cyclopentane
derivative of formula (II) wherein X.sup.3 is an oxygen atom with a
reducing agent, 0.5 to 10 equivalents, especially 0.8 to 5
equivalents of the reducing agent is preferably used relative to
the substituted cyclopentane derivative. Exemplary reducing agents
include sodium boron hydride, sodium boron hydride-cerium
trichloride mixtures, aluminum isobutyl hydride, aluminum lithium
hydride, aluminum hydride, trialkoxyaluminum lithium hydride (the
alkoxy moieties may be the same or different and include, for
example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, t-butoxy,
ethylenedioxy, 1,2-diphenylethylenedioxy, and propylenedioxy), zinc
boron hydride, K-selectride, L-selectride, Red-Al, and
triethylsilane. There may be used any of reaction solvents which do
not inhibit reaction, for example, methanol, ethanol, isopropanol,
benzene, hexane, methylene chloride, tetrahydrofuran (THF),
toluene, 1,4-dioxane, diethyl ether, and dimethoxyethane (DME)
alone or in admixture. The reaction temperature ranges from
-100.degree. C. to the reflux temperature of the solvent, usually
from -80.degree. C. to 50.degree. C. The reaction time is usually
from 5 minutes to 50 hours although it varies with the substrate,
solvent and reaction temperature.
[0101] With regard to the reaction of a substituted cyclopentene
derivative of formula (II) with a halide of formula (III), 1 to 5
equivalents, especially 1.5 to 3 equivalents of the halide of
formula (III) is preferably used relative to the substituted
cyclopentene derivative of formula (II). Preferred examples of the
halide of formula (III) to be combined include sodium bromide,
potassium bromide, sodium iodide, potassium iodide, and
tetrabutylammonium bromide. In reaction scheme A, reaction of the
compound of formula (II) with the compound of formula (III) may be
carried out in the presence or absence of a Lewis acid. Examples of
the Lewis acid include boron trifluoride-diethyl ether complexes,
trialkoxyaluminum, tetraalkoxytitanium, tetrahalotitanium,
monoalkoxytrihalotitanium, dialkoxydihalotitanium,
trialkoxyhalotitanium (the halo moieties, which may be the same or
different, include fluorine, chlorine, bromine and iodine, and the
alkoxy radicals, which may be the same or different, include
methoxy, ethoxy, propoxy, isopropoxy, butoxy, t-butoxy,
ethylenedioxy, 1,2-diphenylethylenedioxy, and propylenedioxy). The
Lewis acid, if present, is used in an amount of 0.5 to 5
equivalents relative to the substituted cyclopentene derivative of
formula (II). It is especially preferred to use 1 to 2 equivalents
of boron trifluoride-diethyl ether complex or
tetraisopropoxytitanium. There may be used any of reaction solvents
which do not inhibit reaction, for example, acetone, benzene,
hexane, methylene chloride, tetrahydrofuran (THF), toluene,
1,4-dioxane, diethyl ether, and dimethoxyethane (DME) alone or in
admixture, with acetone being preferred. The reaction temperature
ranges from -100.degree. C. to the reflux temperature of the
solvent, usually from -20.degree. C. to 50.degree. C. The reaction
time is usually from 5 minutes to 50 hours although it varies with
the substrate, solvent and reaction temperature.
[0102] The halogenated cyclopentene derivatives of formula (I)
which are synthesized from a substituted cyclopentene derivative of
formula (II) and a halide of formula (III) in this way are novel
compounds.
[0103] With regard to the synthesis of organometallic reagents of
formula (IV), those reagents wherein R.sup.3 in
CR.sup.1R.sup.2CR.sup.3R.sup.4 or CR.sup.1.dbd.CR.sup.2 is a
hydrogen atom and M.sup.2 is a substituted borane radical can be
synthesized by adding corresponding boron hydrides to those
reagents wherein U is CR.sup.1.ident.C. The alkenyl boron compounds
in cis form of formula (IV) can be synthesized in accordance with
the reports of Negishi and Suzuki (E. Negishi et al., J. Organomet.
Chem., 92, C4 (1975), A. Suzuki et al., Chem. Rev., 1995, 95,
2457).
[0104] In reaction scheme B, the reaction of a substituted
cyclopentene derivative of formula (I) with an organometallic
reagent of formula (IV) preferably uses 1 to 10 equivalents,
especially 1.5 to 5 equivalents of the organometallic reagent of
formula (IV) relative to the substituted cyclopentene derivative of
formula (I). The metal catalyst, if used, is preferably added in an
amount of 0.001 to 1 equivalent, especially 0.01 to 0.1 equivalent
relative to the substituted cyclopentene derivative of formula (I).
Examples of the metal catalyst include Pd(PPh.sub.3).sub.4,
Pd.sub.2(dba).sub.3--CHCl.sub.3 wherein dba is dibenzalacetone,
Pd(OCOMe).sub.2, PdCl.sub.2, PdCl.sub.2(PPh.sub.3).sub.2,
PdCl.sub.2(dppf) wherein dppf is
1,1'-bisdiphenylphosphinoferrocene, Na.sub.2PdCl.sub.4,
PdCl.sub.2(MeCN).sub.2, Ni(PPh.sub.3).sub.4, Ni(COD).sub.2 wherein
COD is cyclooctadiene, and NiCl.sub.2. If necessary, a phosphine
ligand is preferably used in an amount of 0.001 to 1 equivalent,
especially 0.01 to 1 equivalent relative to the substituted
cyclopentene derivative of formula (I). Examples of the phosphine
ligand include triphenylphosphine, 1,3-bisdiphenylphosphinopropane,
1,2-bisdiphenylphosphinobutane,
2,2'-bisdiphenylphosphino-1,1'-binaphthyl- , and
1,1'-bisdiphenylphosphinoferrocene. There may be used any of
reaction solvents which do not inhibit reaction, for example,
acetone, benzene, hexane, methylene chloride, 1,2-dichloroethane,
THF, toluene, 1,4-dioxane, diethyl ether, and DME alone or in
admixture, with benzene and THF being preferred. Reaction proceeds
under neutral to basic conditions, preferably under basic
conditions. For the basic catalyst, organic amines such as
triethylamine, pyridine, N-methylmorpholine, and
diaza-bicycloundecene or inorganic bases such as sodium hydroxide,
potassium hydroxide, sodium carbonate, potassium carbonate, sodium
hydrogen carbonate, and potassium hydrogen phosphate may be used
alone or in admixture and if desired, in an aqueous solution form.
While the amount of basic catalyst used varies with a particular
base, the basic catalyst can be used in an amount of 0.001 to 100
equivalents or as a solvent, preferably in an amount of 0.01 to 50
equivalents relative to the compound of formula (I). The reaction
temperature ranges from -100.degree. C. to the reflux temperature
of the solvent, usually from -20.degree. C. to 100.degree. C. The
reaction time is usually from 5 minutes to 50 hours although it
varies with the substrate, solvent and reaction temperature.
[0105] Especially when M.sup.2 is a substituted borane or
substituted stannyl radical, the metal catalyst is preferably
selected from Pd(PPh.sub.3).sub.4, Pd.sub.2(dba).sub.3--CHCl.sub.3,
Pd(OCOMe).sub.2, PdCl.sub.2, PdCl.sub.2(PPh.sub.3).sub.2, and
PdCl.sub.2(dppf).
[0106] The halogenated cyclopentene derivatives of formula (V)
which are synthesized from a substituted cyclopentene derivative of
formula (I) and an organometallic reagent of formula (IV) in this
way are novel compounds.
[0107] Reaction scheme C involves the reaction of a substituted
cyclopentene derivative of formula (VI) with an oxidizing agent.
Examples of the oxidizing agent include peracids (e.g.,
meta-chloroperbenzoic acid, perbenzoic acid, trifluoroperacetic
acid, and peracetic acid) and combinations of a peroxide and a
metal (exemplary peroxides are hydrogen peroxide,
t-butylhydroperoxide, 1,2,3,4-tetrahydronaphthalene-1-hydropero-
xide, and exemplary metals are vanadium, titanium, molybdenum, and
tungsten in salt form). Preferably 1 to 10 equivalents of the
oxidizing agent is used relative to the substituted cyclopentene
derivative of formula (I), especially 1 to 5 equivalents of the
peracid is used where R.sup.1 in formula (VI) is a substituted
silyl radical. There may be used any of reaction solvents which do
not inhibit reaction, for example, acetone, benzene, hexane,
methylene chloride, 1,2-dichloroethane, THF, toluene, 1,4-dioxane,
diethyl ether, DME, and chloroform alone or in admixture, with
methylene chloride and chloroform being preferred. The reaction
temperature ranges from -100.degree. C. to the reflux temperature
of the solvent, usually from -20.degree. C. to 70.degree. C. The
reaction time is usually from 5 minutes to 50 hours although it
varies with the substrate, solvent and reaction temperature.
[0108] The substituted cyclopentene derivatives of formula (VII)
which are synthesized from a substituted cyclopentene derivative of
formula (VI) and an oxidizing agent are novel compounds.
[0109] Reaction scheme D involves the reaction of a substituted
cyclopentene derivative of formula (VII) with an acid. Examples of
the acid include Lewis acids such as boron trifluoride-diethyl
ether complexes, trialkoxyaluminum, tetraalkoxytitanium,
tetrahalotitanium, monoalkoxytrihalotitanium,
dialkoxydihalotitanium, trialkoxyhalotitanium (the halo moieties,
which may be the same or different, include fluorine, chlorine,
bromine and iodine, and the alkoxy radicals, which may be the same
or different, include methoxy, ethoxy, propoxy, isopropoxy, butoxy,
t-butoxy, ethylenedioxy, 1,2-diphenylethylenedioxy, and
propylenedioxy); mineral acids such as hydrochloric acid and
sulfuric acid; and organic acids such as acetic acid,
para-toluenesulfonic acid, and methanesulfonic acid. Preferably 0.1
to 10 equivalents of the acid is used relative to the substituted
cyclopentene derivative of formula (VII). It is especially
preferred to use 0.5 to 3 equivalents of boron trifluoride-diethyl
ether complex or tetraisopropoxytitanium. There may be used any of
reaction solvents which do not inhibit reaction, for example,
methanol, ethanol, isopropanol, acetone, benzene, hexane, methylene
chloride, 1,2-dichloroethane, THF, toluene, 1,4-dioxane, diethyl
ether, DME, and chloroform alone or in admixture, with methanol,
ethanol, and isopropanol being preferred. The reaction temperature
ranges from -100.degree. C. to the reflux temperature of the
solvent, usually from -20.degree. C. to 70.degree. C. The reaction
time is usually from 5 minutes to 50 hours although it varies with
the substrate, solvent and reaction temperature.
[0110] The present invention ensures easy synthesis of intermediate
substituted cyclopentene derivatives useful for the synthesis of
PG's and facilitates commercially advantageous production of PG's
from the resulting substituted cyclopentene derivatives.
[0111] Examples and Reference Examples are given below by way of
illustration of the invention although the invention is not limited
to these Examples and Reference Examples. In the following
Examples, Me is methyl, Et is ethyl, Ph is phenyl, MOM is
methoxymethyl, dppf is 1,1'-bisdiphenylphosphinoferrocene, and dba
is dibenzalacetone.
EXAMPLE 1
[0112] 35
[0113] In a dry nitrogen atmosphere, boron trifluoride diethyl
ether complex (1.24 ml, 10.1 mmol) was added to a solution of an
enone (1) (2.16 g, 7.54 mmol) and NaBr (1.73 g, 16.8 mmol) in dry
acetone (28 ml) at room temperature and stirred for 11/2 hours at
room temperature. The reaction solution was poured into ether (10
ml) and saturated aqueous sodium bicarbonate solution (10 ml).
After the aqueous layer was extracted with ether (10 ml) again, the
organic layer was washed with aqueous sodium thiosulfate solution
and dried over anhydrous magnesium sulfate, and the solvent was
distilled off in vacuum. The residue was purified by silica gel
column chromatography, obtaining an end compound (2a) in an amount
of 2.04 g (yield 89%). Analytical data of compound (2a) are shown
below.
[0114] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta.
7.38-7.41 (m, 1H), 4.91-4.97 (m, 1H), 4.02 (s, 2H), 2.83 (dd,
J=6.0, 18.0 Hz, 1H), 2.36 (dd, J=18.0, 2.2 Hz, 1H), 0.90 (s, 9H),
0.12 and 0.14 (2s, 6H)
[0115] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. 202.8, 160.5,
142.9, 68.6, 45.6, 25.9, 21.0, 18.1, -4.7 (2C)
[0116] IR (neat) 2930, 2852, 1710, 1460, 1342, 1250, 1082, 906,
830, 775
[0117] [.alpha.].sup.23.sub.D+26.3 (c 0.96, CHCl.sub.3)
EXAMPLE 2
[0118] 36
[0119] In a dry nitrogen atmosphere, boron trifluoride diethyl
ether complex (0.87 ml, 7.08 mmol) was added to a solution of an
enone (1) (1.30 g, 4.54 mmol) and NaI (1.77 g, 11.8 mmol) in dry
acetone (20 ml) at room temperature and stirred for 11/2 hours at
room temperature. The reaction solution was poured into ether (10
ml) and saturated aqueous sodium bicarbonate solution (10 ml).
After the aqueous layer was extracted with ether (10 ml) again, the
organic layer was washed with aqueous sodium thiosulfate solution
and dried over anhydrous magnesium sulfate, and the solvent was
distilled off in vacuum. The residue was purified by silica gel
column chromatography, obtaining 1.02 g (yield 64%) of an end
compound (2b). Analytical data of compound (2b) are shown
below.
[0120] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. 7.38
(d, J=2.5 Hz, 1H), 4.83-4.90 (m, 1H), 3.91 (s, 2H), 2.83 (dd,
J=6.0, 18.4 Hz, 1H), 2.34 (dd, J=2.2, 18.4 Hz, 1H), 0.91 (s, 9H),
0.12 and 0.13 (2s, 6H)
EXAMPLES 3-7
[0121] 37
[0122] In a dry nitrogen atmosphere, a THF solution of 9-BBN
(0.5M.times.4 ml=2 mmol) was slowly added to an acetylene (3) (2
mmol) in dry THF (0.5 ml) at 0.degree. C. The solution was stirred
for more than 12 hours at room temperature, obtaining a THF
solution of a compound (4).
[0123] 4a: R=nC.sub.5H.sub.11, R'=H
[0124] 4b: R=CH.sub.2CH.sub.2CO.sub.2Me, R'=H
[0125] 4c: R=nC.sub.5H.sub.11, R'=SiMe.sub.3
[0126] 4d: R=CH.sub.2CH.sub.2CO.sub.2Me, R'=SiMe.sub.3
[0127] 4e: R=CH.dbd.CHCO.sub.2Me, R'=SiMe.sub.3
EXAMPLES 8-9
[0128] 38
[0129] In a dry nitrogen atmosphere, 3.3 ml of borane-THF complex
(1 M) was ice cooled, and 0.66 ml (6.6 ml) of cyclohexene was
slowly added dropwise thereto and stirred at the temperature for
11/2 hours. Under ice cooling, an acetylene (3) (3 mmol) in dry THF
(4 ml) was slowly added thereto and stirred at the temperature for
20 minutes. The reaction mixture was stirred for 1 hour at room
temperature, obtaining a THF solution of a compound (4').
[0130] 4'd: R=CH.sub.2CH.sub.2CO.sub.2Me, R'=SiMe.sub.3
[0131] 4'e: R=CH.dbd.CHCO.sub.2Me, R'=SiMe.sub.3
EXAMPLE 10
[0132] 39
[0133] In a dry nitrogen atmosphere, Pd(PPh.sub.3).sub.4 (5.8 mg, 5
mol %) was added to an enone (2a) (30.5 mg, 0.1 mmol) in dry
benzene and stirred for 10 minutes. A solution of the
above-obtained compound (4a) wherein R=nC.sub.5H.sub.11 and R'=H in
THF (0.4M .times.0.5 ml=0.2 mmol) and an aqueous NaOH solution
(2M.times.0.2 ml=0.4 mmol) were added thereto. The reaction mixture
was heated under reflux for 2 hours. The reaction mixture was
cooled to room temperature again, whereupon hexane (1 ml) and
aqueous ammonium chloride solution (1 ml) were added thereto. After
extraction, the organic layer was dried over anhydrous magnesium
sulfate, and the solvent was distilled off under vacuum. The
residue was purified by silica gel column chromatography, obtaining
an end compound (5a) in an amount of 21.7 mg (yield 65%).
Analytical data of compound (5a) are shown below.
[0134] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. 7.03
(br, s, 1H), 5.37-5.58 (m, 2H), 4.86-4.93 (m, 1H), 2.86 (d, J=5.4
Hz, 1H), 2.79 (dd, J=4.8, 14.4 Hz, 1H), 2.29 (d, J=14.4 Hz, 1H),
2.01 (dt, J=6.8, 5.4 Hz, 1H), 1.12-1.68 (m, 8H), 0.84-0.92 (m, 3H),
0.91 (s, 9H), 0.11 and 0.13 (2s, 6H)
EXAMPLE 11
[0135] 40
[0136] In a dry nitrogen atmosphere, Pd(PPh.sub.3).sub.4 (5.8 mg, 5
mol %) was added to an enone (2a) (30.5 mg, 0.1 mmol) in dry
benzene and stirred for 10 minutes. A solution of the
above-obtained compound (4b) wherein R=CH.sub.2CH.sub.2CO.sub.3Me
and R'=H in THF (0.4M.times.0.5 ml=0.2 mmol) and an aqueous NaOH
solution (4M.times.0.2 ml=0.8 mmol) were added thereto. The
reaction mixture was heated under reflux for 4 hours. The reaction
mixture was cooled to room temperature again, diluted with ether (2
ml), and adjusted to pH 6 with an aqueous solution of 1N HCl. After
extraction, the organic layer was washed with saturated aqueous
sodium chloride solution and dried over anhydrous magnesium
sulfate, and the solvent was distilled off under vacuum. The
residue was quantitatively determined by .sup.1H-NMR spectroscopy
(internal standard: mesitylene), obtaining an end compound (5b) in
a yield of 48%. Analytical data of compound (5b) are shown
below.
[0137] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. 7.05
(br, s, 1H), 5.41-5.53 (m, 2H), 4.86-4.92 (m, 1H), 3.67 (s, 3H),
2.87 (br, s, 2H), 2.76 (dd, J=4.8, 15.0 Hz, 1H), 2.24-2.41 (m, 5H),
2.02-2.13 (m, 2H), 0.91 (s, 9H), 0.12 (s, 6H)
EXAMPLE 12
[0138] 41
[0139] As in Example 11, a compound (5c) was obtained using a
compound (4c) wherein R=nC.sub.5H.sub.11 and R'=SiMe.sub.3.
Analytical data of compound (5c) are shown below.
[0140] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. 6.92
(br, s, 1H), 5.99 (t, J=6.3 Hz, 1H), 4.82-4.94 (m, 1H), 2.89 (br,
s, 1H), 2.76 (dd, J=4.8, 15.0 Hz, 1H), 2.30 (d, J=15.0 Hz, 1H),
2.02-2.25 (m, 2H), 1.20-1.95 (m, 8H), 0.84-0.06 (m, 3H), 0.91 (s,
9H), 0.11 (s, 6H)
EXAMPLE 13
[0141] 42
[0142] In a dry nitrogen atmosphere, Pd(PPh.sub.3).sub.4 (5.8 mg, 5
mol %) was added to an enone (2a) (30.5 mg, 0.1 mmol) in dry
benzene and stirred for 10 minutes. A solution of the
above-obtained compound (4d) wherein R=CH.sub.2CH.sub.2COOMe and
R'=SiMe.sub.3 in THF (0.4M.times.0.5 ml=0.2 mmol) and an aqueous
NaOH solution (4M.times.0.2 ml=0.8 mmol) were added thereto. The
reaction mixture was heated under reflux for 4 hours. The reaction
mixture was cooled to room temperature again, diluted with ether (2
ml), and adjusted to pH 6 with an aqueous solution of 1N HCl. After
extraction, the organic layer was washed with saturated sodium
chloride solution and dried over anhydrous magnesium sulfate, and
the solvent was distilled off under vacuum. The residue was
purified by silica gel column chromatography and quantitatively
determined by .sup.1H-NMR spectroscopy (internal standard:
mesitylene), obtaining an end compound (5d) in a yield of 62%.
Analytical data of compound (5d) are shown below.
[0143] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta.
6.88-6.93 (m, 1H), 5.93 (t, J=7.20 Hz, 1H), 4.82-4.88 (m, 1H), 3.67
(s, 3H), 2.80-2.95 (m, 2H), 2.74 (dd, J=18.3, 5.9 Hz, 1H), 2.33 (t,
J=7.5 Hz, 1H), 2.15-2.25 (m, 3H), 1.65-1.77 (m, 2H), 0.89 (s, 9H),
0.08 (s, 9H), 0.09 and 0.11 (2s, 6H)
[0144] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. 205.5, 173.8,
157.8, 147.2, 144.6, 136.4, 68.7, 51.5, 45.7, 33.5, 32.8, 31.3,
25.7, 25.1, 18.0, 0.13 (3C), -4.71 (2C)
[0145] IR (neat) 2960, 2852, 1710, 1435, 1350, 1248, 1160, 1078,
835, 775
[0146] [.alpha.].sup.23.sub.D+5.54 (c 1.03, CHCl.sub.3)
EXAMPLE 14
[0147] 43
[0148] In a dry nitrogen atmosphere, Pd(PPh.sub.3).sub.4 (94.7 mg,
5 mol %) was added to an enone (2a) (500 mg, 1.64 mmol) in 16.4 ml
of dry benzene and stirred for 10 minutes. A solution of the
above-obtained compound (4'd) wherein R=CH.sub.2CH.sub.2CO.sub.3Me
and R'=SiMe.sub.3 in THF (0.35M.times.8.56 ml=3 mmol) and an
aqueous NaOH solution (3M .times.1.1 ml=3.3 mmol) were added
thereto. The reaction mixture was heated under reflux for 11/2
hours. The reaction mixture was cooled to room temperature again,
diluted with ether (2 ml), and adjusted to pH 6 with an aqueous
solution of 1N HCl. After extraction, the organic layer was washed
with saturated sodium chloride solution and dried over anhydrous
magnesium sulfate. The solvent was distilled off under vacuum,
obtaining an end compound (5d) in an amount of 2.20 g (yield
92%).
EXAMPLE 15
[0149] 44
[0150] In a dry nitrogen atmosphere, Pd(PPh.sub.3).sub.4 (102 mg, 3
mol %) was added to an enone (2a) (900 mg, 2.94 mmol) in dry
benzene and stirred for 10 minutes. A solution of the
above-obtained compound (4'e) wherein R=CH.dbd.CHCOOMe and
R'=SiMe.sub.3 in THF (0.35M.times.11.3 ml=4.0 mmol) and an aqueous
NaOH solution (3M.times.2.7 ml=8.0 mmol) were added thereto. The
reaction mixture was heated under reflux for 30 minutes. The
reaction mixture was cooled to room temperature again, diluted with
ether, and adjusted to pH 6 with an aqueous solution of 1N HCl.
After extraction, the organic layer was washed with saturated
aqueous sodium bicarbonate and dried over anhydrous magnesium
sulfate. The solvent was distilled off under vacuum, obtaining an
end compound (5e). Analytical data of compound (5e) are shown
below.
[0151] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. 6.96
(dt, J=15.7, 6.2 Hz, 1H), 6.89-6.94 (m, 1H), 5.94 (t, J=7.5 Hz,
1H), 5.83 (dt, J=15.7, 1.7 Hz, 1H), 4.81-4.92 (m, 1H), 3.72 (s,
3H), 3.03-3.11 (m, 2H), 2.88-3.01 (m, 2H), 2.75 (dd, J=5.9, 18.3
Hz, 1H), 2.28 (dd, J=2.0, 18.3 Hz, 1H), 0.88 (s, 9H), 0.09 and 0.10
(2s, 15H)
[0152] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. 205.4, 166.8,
158.0, 146.7, 146.6, 139.4, 139.1, 121.5, 68.7, 51.4, 45.6, 34.5,
32.7, 25.7, 18.0, 0.09 (3C), -4.7 (2C)
[0153] IR (neat) 2930, 2870, 1718, 1660, 1620, 1470, 1440, 1410,
1350, 1330, 1260, 1200, 1170, 1080, 1010, 910, 840, 780, 760
[0154] [.alpha.].sup.23.sub.D+2.14 (c 0.58, CHCl.sub.3)
EXAMPLES 16-17
[0155] 45
[0156] In a dry nitrogen atmosphere, a THF solution of 9-BBN
(0.5M.times.4 ml 2 mmol) was slowly added to 1-iodo-1-acetylene (6)
(2 mmol) in dry THF (0.5 ml) at 0.degree. C. The solution was
stirred at room temperature for more than 12 hours and then cooled
to -78.degree. C., and a THF solution of lithium
triethylborohydride (1.0M.times.2 ml=2 mmol) was added thereto. The
mixture was heated up to room temperature over more than 3 hours,
obtaining a THF solution of a compound (7)
[0157] 7a: R=nC.sub.5H.sub.11
[0158] 7b: R=CH.sub.2CH.sub.2CO.sub.2Me
EXAMPLE 18
[0159] 46
[0160] In a dry nitrogen atmosphere, Pd(PPh.sub.3).sub.4 (5.8 mg, 5
mol %) was added to an enone (2a) (30.5 mg, 0.1 mmol) in dry
benzene and stirred for 10 minutes. A solution of the
above-obtained compound (7a) (R=nC.sub.5H.sub.11) in THF
(0.29M.times.2 ml=0.58 mmol) and an aqueous NaOH solution
(2M.times.0.3 ml=0.6 mmol) were stirred for 1 minute, with the
aqueous layer separated off, and added thereto. The reaction
mixture was combined with an aqueous NaOH solution (2M.times.0.2
ml=0.4 mmol) and heated under reflux for 2 hours. The reaction
mixture was cooled to room temperature again, and hexane (1 ml) and
aqueous ammonium chloride solution (1 ml) were added thereto. After
extraction, the organic layer was dried over anhydrous magnesium
sulfate, and the solvent was distilled off under vacuum. The
residue was purified by silica gel column chromatography, obtaining
an end compound (8a) in an amount of 20.6 mg (yield 61%).
Analytical data of compound (8a) are shown below.
[0161] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. 7.03
(br, s, 1H), 5.30-5.68 (m, 2H), 4.82-4.93 (m, 1H), 2.91 (d, J=7.1
Hz, 1H), 2.76 (dd, J=5.9, 18.2 Hz, 1H), 2.29 (dd, J=2.1, 18.2 Hz,
1H), 2.04 (dt, J=6.8, 7.1 Hz, 1H), 1.17-1.65 (m, 8H), 0.91 (s, 9H),
0.88 (t, J=6.0 Hz, 3H), 0.11 and 0.12 (2s, 6H)
EXAMPLE 19
[0162] 47
[0163] In a dry nitrogen atmosphere, Pd(PPh.sub.3).sub.4 (5.8 mg, 5
mol %) was added to an enone (2a) (30.5 mg, 0.1 mmol) in dry
benzene and stirred for 10 minutes. A solution of the
above-obtained compound (7b) wherein R=CH.sub.2CH.sub.2CO.sub.2Me
in THF (0.29M.times.0.73 ml=0.21 mmol) and an aqueous NaOH solution
(4M.times.0.3 ml=1.2 mmol) were stirred for 1 minute, with the
aqueous layer separated off, and added thereto. The reaction
mixture was combined with an aqueous NaOH solution (4M.times.0.2
ml=0.8 mmol) and heated under reflux for 2 hours. The reaction
mixture was cooled to room temperature again, diluted with ether (2
ml), and adjusted to pH 6 with an aqueous solution of 1N HCl. After
extraction, the organic layer was washed with saturated aqueous
sodium chloride solution and dried over anhydrous magnesium
sulfate, and the solvent was distilled off under vacuum. The
residue was quantitatively determined by .sup.1H-NMR spectroscopy
(internal standard: mesitylene), obtaining an end compound (8b) in
a yield of 23%. Analytical data of compound (8b) are shown
below.
[0164] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. 7.09
(br, s, 1H), 5.45-5.51 (m, 2H), 4.87 (m, 1H), 3.69 (s, 3H), 2.88
(br, s, 1H), 2.73 (dd, J=4.9, 15 Hz, 1H), 2.18-2.45 (m, 5H), 0.91
(s, 9H), 0.11 (s, 6H)
EXAMPLE 20
[0165] 48
[0166] In a dry nitrogen atmosphere, 13.6 mg (0.079 mmol) of
meta-chloroperbenzoic acid (mCPBA) was added to a compound (5c) (10
mg, 0.026 mmol) in dry methylene chloride under ice cooling. After
restoration to room temperature, the mixture was stirred for 12
hours at room temperature. Reaction was terminated with aqueous
sodium bicarbonate. After extraction with diethyl ether, the
organic layer was washed with saturated aqueous sodium chloride
solution and dried over anhydrous magnesium sulfate, and the
solvent was distilled off under vacuum. Analysis of the residue by
.sup.1H-NMR spectroscopy confirmed an end compound (9c). Analytical
data of compound (9c) are shown below.
[0167] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. 7.21
(br, s, 1H), 4.88 (m, 1H), 2.64-2.81 (m, 3H), 2.39 (t, J=7.6 Hz,
1H), 2.01-2.34 (m, 1H), 1.05-1.73 (m, 10H), 0.80-0.99 (m, 3H), 0.91
(s, 9H), 0.10, 0.12, 0.13 (3s, 15H)
EXAMPLE 21
[0168] 49
[0169] In a dry nitrogen atmosphere, 170 mg (0.981 mmol) of
meta-chloroperbenzoic acid (mCPBA) was added to a compound (5d)
(150 mg, 0.353 mmol) in dry methylene chloride under ice cooling.
After restoration to room temperature, the mixture was stirred for
4 hours at room temperature. Reaction was terminated with aqueous
sodium bicarbonate. After extraction with diethyl ether, the
organic layer was washed with saturated aqueous sodium chloride
solution and dried over anhydrous magnesium sulfate, and the
solvent was distilled off under vacuum. The residue was
quantitatively determined by .sup.1-NMR spectroscopy (internal
standard: Trichlene), obtaining an end compound (9d) in a yield of
95%. Analytical data of compound (9d) are shown below.
[0170] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta.
7.16-7.22 (m, 1H), 4.83-4.91 (m, 1H), 3.67 (s, 3H), 1.60-1.90 (m,
5H), 1.55-1.89 (m, 4H), 1.10-1.55 (m, 7H), 0.89 (s, 9H), 0.08-0.15
(m, 15H)
EXAMPLE 22
[0171] 50
[0172] To a compound (5e) (synthesized from 900 mg of compound (2a)
in Example, starting with 2.94 mmol) in dry methylene chloride
under ice cooling were added 2 ml of 35% hydrogen peroxide and 2.0
ml (0.981 mmol) of a saturated aqueous solution of 3N sodium
hydroxide. After restoration to room temperature, the mixture was
stirred for 4 hours at room temperature. After extraction with
diethyl ether, the organic layer was washed with 1N hydrochloric
acid and saturated aqueous sodium chloride solution and dried over
anhydrous magnesium sulfate, and the solvent was distilled off
under vacuum. The residue was purified by silica gel column
chromatography, obtaining an end compound (9e) in an amount of 1.01
g (two-step yield 81%). Analytical data of compound (9e) are shown
below.
[0173] .sup.1H-NMR (300 MHz, CDCl.sub.3) .delta. 7.16-7.20 (m, 1H),
6.78-7.05 (m, 1H), 5.80-6.02 (m, 1H), 4.85-4.93 (m, 1H), 3.73 (s,
3H), 2.65-2.95 (m, 2H), 2.10-2.60 (m, 5H), 0.89 (s, 9H), 0.08-0.18
(m, 15H)
EXAMPLE 23
[0174] 51
[0175] In a dry nitrogen atmosphere, 30 mg (0.177 mmol) of
meta-chloroperbenzoic acid (mCPBA) was added to a compound (5e) (50
mg, 0.118 mmol) in dry methylene chloride under ice cooling. After
restoration to room temperature, the mixture was stirred for 4
hours at room temperature. Reaction was terminated with aqueous
sodium bicarbonate. After extraction with diethyl ether, the
organic layer was washed with saturated aqueous sodium chloride
solution and dried over anhydrous magnesium sulfate, and the
solvent was distilled off under vacuum. The residue was
quantitatively determined by .sup.1H-NMR spectroscopy (internal
standard: Trichlene), obtaining an end compound (9e) in a yield of
81%.
EXAMPLE 24
[0176] 52
[0177] About 20 mg (0.14 mmol) of boron trifluoride diethyl ether
complex was added to a compound (9c) (about 10 mg, 0.026 mmol) in
MeOH (1 ml) under ice cooling, which was stirred for 20 minutes.
Reaction was terminated with saturated aqueous sodium bicarbonate.
The reaction solution was dried over anhydrous sodium sulfate,
filtered, and washed with diethyl ether, and the solvent was
distilled off under vacuum. Analysis of the residue by .sup.1H-NMR
spectroscopy confirmed an end compound (10c). Analytical data of
compound (10d) are shown below.
[0178] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. 7.32
(br, s, 1H), 4.94-5.00 (m, 1H), 3.18-3.45 (m, 2H), 2.76 (dd, J=6.0,
18.3 Hz, 1H), 2.48 (t, J=7.1 Hz, 2H), 2.27 (dd, J=2.1, 18.3 Hz,
1H), 1.05-1.89 (m, 10H), 0.80-0.98 (m, 3H), 0.90 (s, 9H), 0.13,
0.14 (2s, 6H)
EXAMPLE 25
[0179] 53
[0180] About 20 mg (0.14 mmol) of boron trifluoride diethyl ether
complex was added to a compound (9d) (86 mg, 0.195 mmol) in MeOH
(3.9 ml) under ice cooling, which was stirred for 10 minutes.
Reaction was terminated with saturated aqueous sodium bicarbonate.
After extraction with diethyl ether, the organic layer was washed
with saturated aqueous sodium chloride solution and dried over
anhydrous magnesium sulfate, and the solvent was distilled off
under vacuum. The residue was purified by silica gel column
chromatography, obtaining an end compound (10d) in an amount of
54.3 mg (yield 76%). Analytical data of compound (10d) are shown
below.
[0181] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta.
7.30-7.32 (m, 1H), 4.94-4.99 (m, 1H), 3.65 (s, 3H), 3.39 (d, J=17.3
Hz, 1H), 3.22 (d, J=17.3 Hz, 1H), 2.76 (dd, J=18.3, 5.9 Hz, 1H),
2.48-2.55 (m, 2H), 2.26-2.36 (m, 2H), 2.27 (dd, J=18.3, 2.1 Hz,
1H), 1.55-1.70 (m, 4H), 0.90 (s, 9H), 0.11 and 0.12 (2s, 6H)
[0182] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. 205.6, 205.2,
173.7, 160.3, 139.4, 69.2, 51.5, 44.7, 42.6, 37.7, 33.7, 24.3,
23.0, 25.8, 18.1, -4.7 (2C)
[0183] IR (neat) 2940, 2850, 1710, 1630, 1455, 1430, 1400, 1340,
1240, 1190, 1160, 1079, 960, 906, 828, 768
[0184] [.alpha.].sup.23.sub.D-3.90 (c 0.93, CHCl.sub.3) cl EXAMPLE
26 54
[0185] About 60 mg (0.45 mmol) of boron trifluoride diethyl ether
complex was added to a compound (9e) (771 mg, 2.10 mmol) in MeOH
(21 ml) under ice cooling, which was stirred for 30 minutes.
Reaction was terminated with saturated aqueous sodium bicarbonate.
After extraction with ethyl acetate, the organic layer was washed
with saturated aqueous sodium chloride solution and dried over
anhydrous magnesium sulfate, and the solvent was distilled off
under vacuum. The residue was purified by silica gel column
chromatography, obtaining an end compound (10e) in an amount of 546
mg (yield 71%). Analytical data of compound (10e) are shown
below.
[0186] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta.
7.28-7.39 (m, 1H), 6.90 (dt, J=15.7, 6.8 Hz, 1H), 5.82 (dt, J=15.7,
1.6 Hz, 1H), 4.93-5.04 (m, 1H), 3.71 (s, 3H), 3.41 (d, J=17.2 Hz,
1H), 3.23 (d, J=17.2 Hz, 1H), 2.76 (dd, J=18.3, 5.9 Hz, 1H),
2.62-2.70 (m, 2H), 2.42-2.54 (m, 1H), 27 (dd, J=18.3, 2.1 Hz, 1H),
0.89 (s, 9H), 0.11 and 0.12 (2s, 6H)
[0187] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. 205.1, 204.2,
166.8, 160.5, 147.1, 139.2, 121.8, 69.2, 51.4, 44.7, 40.9, 37.8,
25.9, 25.8, 18.1, -4.7 (2C)
[0188] IR (neat) 2930, 2860, 1710, 1660, 1420, 1350, 1280, 1250,
1200, 1170, 1080, 970, 905, 820, 780
[0189] [.alpha.].sup.23.sub.D+3.89 (c 0.72, CHCl.sub.3)
REFERENCE EXAMPLE
[0190] Compound (10) is important as an intermediate for the
synthesis of 6-keto-PGE's. The synthesis of PGE's from this
intermediate may be in accord with the process of JP-A 228933/1989.
Examples are illustrated below.
REFERENCE EXAMPLE 1
[0191] 55
[0192] In a dry nitrogen atmosphere, 1 ml of a diethyl ether
solution containing 100 mg (0.271 mmol) of compound (17a) was
stirred, 0.32 ml (0.543 mmol, concentration in pentane 1.7 M) of
t-BuLi was added thereto at -78.degree. C., and the mixture was
stirred for 30 minutes at the temperature. Next, 1.25 ml (0.313
mmol, concentration in tetrahydrofuran 0.25 M) of lithium
2-thienylcyanocuprate was added thereto, and the mixture was
stirred for 30 minutes at -78.degree. C. Moreover, a
tetrahydrofuran solution containing 50 mg (0.136 mmol) of compound
(10d) was added dropwise to the mixture at -78.degree. C. The
mixture was warmed up to room temperature in 1 hours. Reaction was
terminated with saturated aqueous ammonium chloride solution. With
diethyl ether added, the reaction solution was stirred for 1 hour
at room temperature. After the organic layer was separated, the
aqueous layer was further extracted with hexane. The organic layer
was dried over magnesium sulfate, concentrated, and then purified
by silica gel column chromatography, obtaining compound (11d) in an
amount of 62 mg (0.101 mmol, yield 75%). Analytical data of
compound (11d) are shown below.
[0193] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. 5.55
(dd, J=15.6, 4.6 Hz, 1H), 5.47 (dd, J=15.6, 6.6 Hz, 1H), 4.02-4.13
(m, 2H), 3.66 (s, 3H), 2.15-2.73 (m, 2H), 1.10-1.73 (m, 12H),
0.86-0.88 (m, 21H), 0.03 and 0.04 (2s, 12H)
[0194] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. 214.2, 207.5,
173.7, 137.0, 128.3, 73.3, 72.5, 53.0, 51.5, 49.8, 46.7, 42.4,
39.9, 38.5, 33.8, 31.8, 25.8, 25.9, 25.0, 24.4, 23.1, 22.6, 14.0,
18.0, 18.2, -4.74, -4.68, -4.58, -4.29 (4C)
[0195] IR (neat) 2925, 2850, 1745, 1720, 1250, 1155, 1100, 1000,
965, 935, 865, 835, 805, 775
[0196] [.alpha.].sup.21.sub.D-38.6 (c 0.46, CHCl.sub.3).sub.--
[0197] This compound is known in the literature. Therefore, we
succeeded in formal overall synthesis of 6-keto-PGE.sub.1.
REFERENCE EXAMPLE 2
[0198] 56
[0199] In a dry nitrogen atmosphere, 4.1 ml of a diethyl ether
solution containing 151 mg (0.410 mmol) of compound (17a) was
stirred, 0.45 ml (0.765 mmol, concentration in pentane 1.7 M) of
t-BuLi was added thereto at -78.degree. C., and the mixture was
stirred for 30 minutes at the temperature. Next, 1.96 ml (0.491
mmol, concentration in tetrahydrofuran 0.25 M) of lithium
2-thienylcyanocuprate was added thereto, and the mixture was
stirred for 30 minutes at -78.degree. C. Moreover, 1 ml of a
diethyl ether solution containing 27 mg (0.0737 mmol) of compound
(10e) was added dropwise to the mixture at -78.degree. C. The
mixture was warmed up to -30.degree. C. in 1 hours. Reaction was
terminated with saturated aqueous ammonium chloride solution. With
diethyl ether added, the reaction solution was stirred for 1 hour
at room temperature. After the organic layer was separated, the
aqueous layer was further extracted with diethyl ether. The organic
layer was dried over magnesium sulfate, concentrated, and then
purified by silica gel column chromatography, obtaining compound
(11e) in an amount of 33.4 mg (yield 76%). Analytical data of
compound (11e) are shown below.
[0200] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. 6.91
(dt, J=15.7, 6.5 Hz, 1H), 5.81 (d, J 15.7 Hz, 1H), 5.55 (dd,
J=15.4, 4.4 Hz, 1H), 5.47 (dd, J=15.4, 6.6 Hz, 1H), 4.03-4.14 (m,
2H), 3.71 (s, 3H), 2.25-2.75 (m, 10H), 1.15-1.50 (m, 8H), 0.86-0.88
(m, 2H), 0.03 and 0.04 (s, 12H)
[0201] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. 214.0, 206.0,
166.7, 147.2, 137.1, 128.1, 121.7, 73.2, 72.5, 53.1, 51.4, 49.9,
46.6, 40.8, 39.8, 38.4, 31.8, 25.7, 25.9, 25.7, 25.0, 22.6, 18.0,
18.2, 14.0, -4.75, -4.70, -4.60, -4.30 (4C)
[0202] IR (neat) 2930, 2860, 1720, 1660, 1485, 1440, 1410, 1370,
1260, 1160, 1100, 1010, 970, 870, 840, 780
[0203] [.alpha.].sup.21.sub.D-43.4 (c 0.67, CDCl.sub.3)
REFERENCE EXAMPLE 3
[0204] 57
[0205] In a dry nitrogen atmosphere, 1.9 ml of an acetonitrile
solution containing 34 mg (0.0558 mmol) of compound (11e) and 0.11
ml of pyridine was stirred, 0.1 ml (about 70 mg, about 3.5 mmol) of
hydrogen fluoride pyridine complex (containing about 70% of
hydrogen fluoride) was added thereto at 0.degree. C., and the
mixture was allowed to warm up to room temperature. Stirring was
continued for 4 hours at room temperature. Reaction was terminated
with saturated aqueous sodium bicarbonate and ethyl acetate was
added. The aqueous layer was saturated with ammonium sulfate, the
organic layer was separated, and the aqueous layer was further
extracted with ethyl acetate. The organic layer was dried over
magnesium sulfate, concentrated, and then purified by silica gel
column chromatography, obtaining compound (12e) in an amount of
20.4 mg (0.0536 mmol, yield 96%). Analytical data of compound (12e)
are shown below.
[0206] .sup.1H-NMR (300 MHz, CDCl.sub.3, (CH.sub.3).sub.4Si)
.delta. 6.90 (dt, J=15.7, 6.6 Hz, 1H), 5.81 (d, J=15.7 Hz, 1H),
5.61 (dd, J=15.2, 6.6 Hz, 1H), 5.51 (dd, J=15.2, 7.8 Hz, 1H),
4.01-4.16 (m, 2H), 3.71 (s, 3H), 2.30-2.83 (m, 10H), 1.15-1.60 (m,
8H), 0.80-0.95 (m, 3H)
[0207] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. 213.0, 206.4,
166.8, 147.2, 137.5, 130.4, 121.7, 72.6, 72.0, 54.2, 51.5, 50.4,
45.1, 40.9, 39.8, 37.2, 31.6, 25.9, 25.1, 22.6, 14.0
[0208] IR (neat) 3375, 2920, 2860, 1710, 1660, 1440, 1410, 1320,
1280, 1200, 1160, 1070, 1040, 970, 850, 750
[0209] [.alpha.].sup.22.sub.D-55.1 (c 0.41, CHCl.sub.3)
REFERENCE EXAMPLE 4
[0210] 58
[0211] To 2.5 ml of phosphoric acid buffer at pH 8 was added 0.5 ml
of an acetone solution containing 20.4 mg (0.0536 mmol) of a
compound (12e). To the solution at room temperature was added 5.3
.mu.l (34 units) of PLE (hog liver esterase, manufactured by Sigma
Co.). Stirring was continued at the temperature for 8 hours. After
the completion of reaction, the solution was adjusted to pH 4 with
0.1N aqueous hydrochloric acid. Ethyl acetate, 5 ml, was added to
the solution, the aqueous layer was saturated with ammonium
sulfate, the organic layer was separated, and the aqueous layer was
further extracted with 5 ml of ethyl acetate. The organic layer was
dried over magnesium sulfate, concentrated, and then purified by
silica gel column chromatography, obtaining compound (13e) in an
amount of 16.6 mg (0.456 mmol, yield 85%). Analytical data of
compound (13e) are shown below.
[0212] .sup.1H-NMR (300 MHz, CDCl.sub.3, (CH.sub.3).sub.4Si)
.delta. 6.95 (dt, J=15.7, 6.3 Hz, 1H), 5.80 (d, J=15.7 Hz, 1H),
5.45-5.65 (m, 2H), 4.01-4.17 (m, 2H), 2.78 (dd, J=18.4, 7.4 Hz,
1H), 2.31-2.72 (m, 9H), 1.05-1.65 (m, 8H), 0.80-1.00 (m, 3H)
[0213] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. 213.2, 206.5,
170.0, 149.0, 137.5, 130.4, 121.6, 72.7, 72.1, 53.9, 50.4, 45.2,
40.6, 40.0, 37.0, 31.6, 26.0, 25.2, 22.6, 14.0
[0214] IR (neat) 3350, 2910, 2849, 1700, 1650, 1400, 1370, 1280,
1240, 1210, 1160, 1070, 960, 850, 750
[0215] [.alpha.].sup.22.sub.D-48.1 (c 0.20, MeOH)
REFERENCE EXAMPLE 5
[0216] 59
[0217] As in Reference Example 1, compound (15d) was obtained by
using compounds (10d) and (17b) and carrying out reaction as shown
above. Analytical data of compound (15d) are shown below.
[0218] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta.
5.43-5.56 (m, 2H), 4.02-4.20 (m, 2H), 3.65 (s, 3H), 2.10-2.70 (m,
10H), 0.98-1.70 (m, 13H), 0.86 and 0.87 (2s, 18H), 0.78-0.92 (m,
6H), 0.01 and 0.04 (2s, 12H)
[0219] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. 214.2, 207.5,
173.7, 136.8, 128.4, 73.4, 71.1, 52.8, 51.5, 49.6, 46.8, 46.2,
42.4, 39.9, 36.8, 33.8, 29.2, 29.1, 25.6, 24.4, 23.1, 18.2, 18.0,
14.1, -4.72, -4.68, -4.57, -4.14 (4C)
[0220] IR (neat) 2930, 2850, 1736, 1718, 1460, 1430, 1360, 1240,
1155, 1095, 1050, 1000, 965, 937, 870, 830, 770
[0221] [.alpha.].sup.21.sub.D-37.5 (c 1.164, CHCl.sub.3)
REFERENCE EXAMPLE 6
[0222] 60
[0223] By carrying out reaction as in Reference Example 3, compound
(16d) was obtained from compound (15d). Analytical data of compound
(16d) are shown below.
[0224] .sup.1H-NMR (300 MHz, CDCl.sub.3, (CH.sub.3).sub.4Si)
.delta. 5.45-5.60 (m, 2H), 4.00-4.18 (m, 2H), 3.65 (s, 3H), 2.75
(dd, J=18.7, 7.5 Hz, 1H), 2.25-2.69 (m, 9H), 1.05-1.70 (m, 13H),
0.81-1.00 (m, 6H)
[0225] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. 213.3, 207.8,
173.8, 137.5, 130.8, 72.0, 71.0, 54.2, 51.5, 50.3, 46.9, 45.2,
42.5, 39.7, 36.6, 33.7, 29.5, 29.1, 24.3, 23.1, 22.9, 19.9,
14.1
[0226] IR (neat) 3400, 2930, 2850, 1720, 1705, 1435, 1400, 1360,
1245, 1200, 1150, 1070, 970, 830, 720
[0227] [.alpha.].sup.23.sub.D-35.1 (c 0.70, CHCl.sub.3)
EXAMPLE 27
[0228] 61
[0229] In a dry nitrogen atmosphere, 0.8 ml (8.0 mmol) of borane
dimethyl sulfide complex (10.0 M, in THF) was dissolved in 4 ml of
dry THF and cooled to 0.degree. C. 2.8 ml (17.6 mmol) of
.alpha.-pinene was added to the solution, which was stirred for 1
hour at the temperature and warmed up to room temperature over 2
hours. The reaction solution was cooled again at -35.degree. C.,
combined with 1.7 g (8.3 mmol) of methyl 6-bromo-5-hexynoate in dry
THF (4.2 ml), and stirred for 11/2 hours at the temperature. The
reaction solution was warmed up to room temperature and stirred for
5 hours. The reaction solution was cooled again at 0.degree. C.,
combined with 7.6 ml (136.3 mmol) of acetaldehyde, and heated under
reflux for 12 hours. The solvent, acetaldehyde and isopinocanphenyl
residue were distilled off under vacuum at room temperature. A
solution of 0.86 ml (6.6 mmol) of 1,3-diol in dry THF (4 ml) was
added at room temperature. The mixture was stirred for 3 hours at
room temperature and the solvent was distilled off under vacuum.
Silica gel short column chromatography yielded 2.3 g of compound
(7c) as an oily matter. The yield was 83%. Analytical data of
compound (7c) are shown below.
[0230] .sup.1H-NMR (300 MHz, CDCl.sub.3, Me.sub.4Si) .delta. ppm
6.72 (t, J=6.9 Hz, 1H), 4.21-4.32 (m, 1H), 3.67 (s, 3H), 2.28-2.39
(m, 4H), 1.71-1.87 (m, 2H), 1.13-1.38 (m, 11H)
EXAMPLE 28
[0231] 62
[0232] In a dry nitrogen atmosphere, 2.0 g (6.0 mmol) of compound
(7c) in diethyl ether (60 ml) was cooled at -5.degree. C. and
combined with a THF solution of KHB(O.sup.iPr).sub.3
(1.0M.times.6.6 ml=6.6 mmol). The mixture was stirred for 15
minutes at 0.degree. C., warmed up to room temperature over 30
minutes, and cooled again to 0.degree. C. 6 ml of water was added
to the solution, which was stirred for 10 minutes and then
separated. After the aqueous layer was extracted twice with 15 ml
of diethyl ether, the organic layer was washed with saturated
aqueous sodium chloride solution and dried over anhydrous magnesium
sulfate, and the solvent was distilled off under vacuum. Silica gel
column chromatography yielded 1.32 g of alkyl borane (7d). The
yield was 87%. Analytical data of compound (7d) are shown
below.
[0233] .sup.1H-NMR (300 MHz, CDCl.sub.3, Me.sub.4Si) .delta. ppm
6.18-6.30 (m, 1H), 5.27 (d, J=13.7 Hz, 1H), 4.16-4.27 (m, 1H), 3.67
(s, 3H), 2.24-2.49 (m, 4H), 1.13-1.89 (m, 13H)
EXAMPLE 29
[0234] 63
[0235] In a dry nitrogen atmosphere, to 140 mg (0.456 mmol) of an
enone (2a) in THF (6 ml) at room temperature were added 8 mg (0.012
mmol) of PdCl.sub.2(dppf), 232 mg (0.912 mmol) of alkylborane (7d),
and 0.22 ml (0.656 mmol) of 3N KOH aqueous solution. The mixture
was heated at 60.degree. C. for 30 minutes. The reaction solution
was cooled back to room temperature and twice extracted with 5 ml
of diethyl ether. The organic layer was washed with 3 ml of 1N HCl
aqueous solution, washed with 5 ml of saturated aqueous sodium
chloride solution, and dried over anhydrous magnesium sulfate, and
the solvent was distilled off under vacuum. Purification by silica
gel column chromatography yielded 133 mg of an enone (8b) as an
oily matter. The yield was 83%. Analytical data of compound (8b)
are shown below.
[0236] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. ppm
6.99-7.08 (m, 1H), 5.41-5.53 (m, 2H), 4.83-4.89 (m, 1H), 3.63 (s,
3H), 2.85-2.91 (m, 1H), 2.76 (dd, J=18.3, 5.9 Hz, 1H), 2.28 (t,
J=7.5 Hz, 2H), 2.26 (dd, J=18.2, 1.9 Hz, 1H), 2.01-2.11 (m, 2H),
1.62-1.72 (m, 2H), 0.88 (s, 9H), 0.09-0.11 (2s, 6H)
[0237] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. ppm 205.5, 173.8,
156.8, 145.2, 131.0, 125.5, 68.9, 51.4, 45.4, 33.3, 26.5, 25.7
(3c), 24.6, 22.6, 18.1, -4.73 (2c)
[0238] IR (neat) cm.sup.-1 2940, 2920, 2870, 2840, 1730, 1700,
1458, 1430, 1350, 1250, 1190
[0239] [.alpha.].sup.25.sub.D+11.1 (c 1.06, CHCl.sub.3)
REFERENCE EXAMPLE 7
[0240] 64
[0241] In a nitrogen atmosphere, 0.38 ml (0.652 mmol, concentration
in pentane 1.70 M) of t-BuLi was added to 120.1 mg (0.326 mmol) of
compound (17a) in diethyl ether (2 ml) at -78.degree. C. and
stirred for 30 minutes at the temperature. Next, 1.56 ml (0.391
mmol, concentration in tetrahydrofuran 0.25 M) of lithium
2-thienylcyanocuprate was added thereto, and the mixture was
stirred for 20 minutes at -78.degree. C. Moreover, 80.0 mg (0.217
mmol) of an enone (8b) in 1 ml of diethyl ether was added dropwise
to the mixture at -78.degree. C. The mixture was warmed up to
0.degree. C. over 2 hours. Reaction was terminated with saturated
aqueous ammonium chloride solution and 5 ml of hexane was added for
extraction. The aqueous layer was further extracted with 5 ml of
hexane. The organic layer was dried over magnesium sulfate,
concentrated, and then purified by silica gel column
chromatography, obtaining 133 mg of compound (9b) as an oily
matter. The yield was 75%. Analytical data of compound (9b) are
shown below.
[0242] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. ppm
5.59 (dd, J=15.7, 4.0 Hz, 1H), 5.50 (dd, J=15.8, 7.1 Hz, 1H),
5.27-5.45 (m, 2H), 4.01-4.13 (m, 2H), 3.66 (s, 3H), 2.63 (dd,
J=18.1, 7.0 Hz, 1H), 2.30 (t, J=7.4 Hz, 2H), 1.99-2.53 (m, 7H),
1.10-1.80 (m, 10H), 0.78-0.96 (m, 3H), 0.88 and 0.89 (2s, 18H),
0.05 and 0.07 (2s, 12H)
[0243] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. ppm 215.2, 173.9,
136.4, 130.6, 128.6, 126.7, 73.2, 72.6, 53.9, 52.7, 51.3, 47.7,
38.5, 33.4, 31.8, 26.6, 25.9, 25.8, 25.2, 25.0, 24.7, 22.6, 18.2
(3c), 18.0 (3c), 14.0, -4.32, -4.63, -4.69, -4.75
[0244] IR (neat) cm.sup.-1 2950, 2925, 2850, 1740, 1460, 1430,
1357, 1250, 1150, 1110, 1090, 1000, 960, 900, 830, 767, 720,
[0245] [.alpha.].sup.25.sub.D+48.6 (c 1.08, CH.sub.3OH)
REFERENCE EXAMPLE 8
[0246] 65
[0247] In a nitrogen atmosphere, 1.1 ml of pyridine and 0.96 ml of
hydrogen fluoride-pyridine complex (containing about 70% of
hydrogen fluoride) were added to 336 mg (0.565 mmol) of compound
(9b) in 20 ml of acetonitrile at 0.degree. C. The mixture was
warmed up to room temperature and stirred for 2 hours at room
temperature. The solution was added dropwise to a mixture of 20 ml
of saturated aqueous sodium bicarbonate and 20 ml of ethyl acetate.
After the organic layer was separated, the aqueous layer was
further extracted with 10 ml of ethyl acetate. The organic layers
were combined, washed with 8 ml of saturated aqueous sodium
bicarbonate, dried over magnesium sulfate, concentrated, and then
purified by silica gel column chromatography, obtaining 160 mg of
compound (10b) as an oily matter. The yield was 80%. Analytical
data of compound (10b) are shown below.
[0248] .sup.1H-NMR (300 MHz, CDCl.sub.3, Me.sub.4Si) .delta. ppm
5.67 (dd, J=15.3, 6.5 Hz, 1H), 5.57 (dd, J=15.2, 7.6 Hz, 1H),
5.28-5.45 (m, 2H), 4.04-4.15 (m, 2H), 3.66 (s, 3H), 2.75 (dd,
J=18.5, 7.2 Hz, 1H), 2.30 (t, J=7.4 Hz, 2H), 2.00-2.43 (m, 7H),
1.25-1.71 (m, 10H), 0.89 (t, J=6.8 Hz, 3H)
REFERENCE EXAMPLE 9
[0249] 66
[0250] To 152 mg (0.415 mmol) of PGE.sub.2 methyl ester (10b) were
added 18 ml of phosphoric acid buffer
(KH.sub.2PO.sub.4--Na.sub.2HPO.sub.4, 1 M, pH 8.0) and 8 ml of
acetone. To this solution, 0.21 ml of Polcine Liver Esterase (785
units, in aqueous (NH.sub.4).sub.2SO.sub.4 solution) was added at
room temperature, followed by rigorous stirring at room temperature
for 6 hours. The solution was adjusted to pH 4 with an aqueous
solution of 1N HCl, and (NH.sub.4).sub.2SO.sub.4 was added until it
was saturated. The solution was extracted twice with 25 ml of ethyl
acetate. The organic layers were combined, washed with 5 ml of
saturated aqueous sodium chloride solution, dried over magnesium
sulfate, concentrated, and purified by silica gel column
chromatography, obtaining 146 mg of compound (10c) as an oily
matter. The yield was 91%. Analytical data of compound (10c) are
shown below.
[0251] .sup.1H-NMR (300 MHz, CDCl.sub.3, Me.sub.4Si) .delta. ppm
5.67 (dd, J=15.3, 6.5 Hz, 1H), 5.57 (dd, J=15.2, 7.6 Hz, 1H),
5.31-5.46 (m, 2H), 4.00-4.17 (m, 2H), 2.75 (dd, J=18.5, 7.2 Hz,
1H), 2.33 (t, J=6.8 Hz, 2H), 1.95-2.43 (m, 7H), 1.25-1.73 (m, 10H),
0.89 (t, J=6.7 Hz, 3H)
[0252] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. ppm 214.6, 177.2,
136.6, 131.2, 130.8, 126.7, 73.1, 72.0, 54.4, 53.4, 46.2, 36.9,
33.1, 31.6, 26.4, 25.2, 25.1, 24.5, 22.6, 14.0
[0253] This compound is a naturally occurring one and known in the
literature. The overall synthesis of PGE.sub.2 was thus
successful.
REFERENCE EXAMPLE 10
[0254] 67
[0255] By following the same process as compound (7c), trans
compound (7'd) was obtained in a yield of 72% from methyl
5-hexynoate. Analytical data of compound (7'd) are shown below.
[0256] .sup.1H-NMR (300 MHz, CDCl.sub.3, Me.sub.4Si) .delta. ppm
6.47 (dt, J=17.6, 6.4 Hz, 1H), 5.36 (dt, J=17.7, 1.5 Hz, 1H),
4.10-4.27 (m, 1H), 3.65 (s, 3H), 2.15-2.40 (m, 4H), 1.15-1.82 (m,
13H)
REFERENCE EXAMPLE 11
[0257] 68
[0258] By following the same process as compound (8b), trans
compound (8'b) was obtained in a yield of 72% from compound (7'd).
Analytical data of compound (8'b) are shown below.
[0259] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. ppm
7.01-7.04 (m, 1H), 5.43-5.49 (m, 2H), 4.85-4.90 (m, 1H), 3.65 (s,
3H), 2.83-2.88 (m, 2H), 2.74 (dd, J=18.3, 5.9 Hz, 1H), 2.30 (t,
J=7.5 Hz, 2H), 2.27 (dd, J=18.3, 2.1 Hz, 1H), 2.00-2.09 (m, 2H),
1.62-1.75 (m, 2H), 0.90 (s, 9H), 0.01 and 0.11 (2s, 11H)
[0260] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. ppm 205.5, 174.0,
157.1, 145.9, 132.0, 126.2, 69.0, 51.4, 45.5, 33.3, 31.7, 27.7,
25.8, 24.4, 18.1, -4.70 (2c)
[0261] IR (neat) cm.sup.-1 2960, 2940, 2865, 1740, 1720, 1640,
1470, 1440, 1370, 1300, 1260, 1200, 1170, 1080, 1010, 970, 903,
840, 820, 780, 670
[0262] [.alpha.].sup.24.sub.D+10.5 (c 0.97, CHCl.sub.3).sub.--
EXAMPLE 32
[0263] 69
[0264] In a dry nitrogen atmosphere, 6.3 mg (0.0086 mmol) of
PdCl.sub.2(dppf), 201 mg (0.684 mmol) of alkylborane (7f) and 0.33
ml (1.026 mmol) of an aqueous 3N KOH solution were added to 105 mg
(0.342 mmol) of an enone (2a) in 3.6 ml of THF at room temperature
and heated at 50.degree. C. for 1 hour. The reaction solution was
cooled back to room temperature, and extracted twice with 5 ml of
diethyl ether. The organic layer was washed with 3 ml of an aqueous
solution of 1N HCl and then with 5 ml of saturated aqueous sodium
chloride solution and dried over anhydrous magnesium sulfate, and
the solvent was distilled off in vacuum. Silica gel column
chromatography gave 109 mg of compound (10f). The yield was 81%.
Analytical data of compound (10f) are shown below.
[0265] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. ppm
5.72-5.82 (m, 1H), 5.43-5.63 (m, 3H), 4.86-4.91 (m, 1H), 4.49 (d,
J=6.4 Hz), and 4.63 (d, J=6.8 Hz, 2H), 2.75 (dd, J=18.3, 5.9 Hz,
1H), 2.31 (t, J=7.6 Hz, 2H), 2.28 (dd, J=18.3, 2.0 Hz, 1H),
2.05-2.13 (m, 2H), 1.64-1.76 (m, 5H), 0.90 (s, 9H), 0.11 and 0.12
(2s, 6H)
[0266] .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. ppm 205.5, 173.2,
156.8, 145.7, 131.2, 131.1, 129.4, 129.3, 125.5, 125.2, 69.0, 59.9,
45.5, 33.6, 26.5, 25.8 (3c), 24.6, 22.6, 18.1, 17.7, -4.71 (2c)
[0267] IR (neat) cm.sup.-1 2970, 2950, 2870, 1740, 1720, 1475,
1395, 1360, 1265, 1200, 1170, 1095, 1050, 1020, 980, 910, 845, 820,
785
[0268] [.alpha.].sup.25.sub.D+11.3 (c 0.96, CDCl.sub.3).sub.--
REFERENCE EXAMPLE 12
[0269] 70
[0270] In a dry nitrogen atmosphere, 0.9 ml (1.528 mmol,
concentration in pentane 1.70 M) of t-BuLi was added to 281 mg
(0.764 mmol) of compound (17a) in 3.82 ml of diethyl ether at
-78.degree. C., and the mixture was stirred for 30 minutes at the
temperature. Next, 3.66 ml (0.916 mmol, concentration in
tetrahydrofuran 0.25 M) of lithium 2-thienylcyanocuprate was added
thereto, and the mixture was stirred for 30 minutes at -78.degree.
C. Moreover, 1 ml of a diethyl ether solution containing 107 mg
(0.273 mmol) of an enone (10f) was added dropwise to the mixture at
-78.degree. C. The mixture was warmed up to 0.degree. C. over 2
hours. Reaction was terminated with 5 ml of saturated aqueous
ammonium chloride solution, and 5 ml of diethyl ether was added for
extraction. The aqueous layer was further extracted with 5 ml of
diethyl ether. The organic layer was dried over magnesium sulfate,
concentrated, and then purified by silica gel column
chromatography, obtaining 151 mg of compound (11f) as an oily
matter. The yield was 87%. Analytical data of compound (11f) are
shown below.
[0271] .sup.1H-NMR (300 MHz, CDCl.sub.3, CHCl.sub.3) .delta. ppm
5.71-5.82 (m, 1H), 5.29-5.63 (m, 3H), 4.49 (d, J=6.5 Hz) and 4.63
(d, J=6.8 Hz, 2H), 4.01-4.13 (m, 2H), 2.63 (dd, J=18.4, 7.1 Hz,
1H), 2.29 (t, J=7.7 Hz, 2H), 1.97-2.53 (m, 7H), 1.13-1.80 (m, 13H),
0.81-0.98 (m, 3H), 0.87 and 0.89 (2s, 18H), 0.04 and 0.05 (2s,
12H)
REFERENCE EXAMPLE 13
[0272] 71
[0273] In a dry argon atmosphere, 0.022 ml (0.579 mmol) of formic
acid, 0.07 ml (0.492 mmol) of triethylamine, and 0.0163 ml (0.0656
mmol) of tributylphosphine were added to 17 mg (0.0164 mmol) of
Pd.sub.2(dba).sub.3.multidot.CHCl.sub.3 in 2.2 ml of dry THF at
room temperature, which was stirred for 30 minutes. A solution of
100 mg (0.16 mmol) of compound (11f) in 1 ml of THF was added
thereto and stirred for 40 minutes at 40.degree. C. Reaction was
terminated with 5 ml of aqueous 1N hydrochloric acid. After the
aqueous layer was twice extracted with diethyl ether, the organic
layer was washed with saturated aqueous sodium chloride solution
and dried over anhydrous magnesium sulfate, and the solvent was
distilled off under vacuum. Silica gel column chromatography gave
75 mg of compound (12f). The yield was 82%. Analytical data of
compound (12f) are shown below.
[0274] .sup.1H-NMR (300 MHz, CDCl.sub.3, Me.sub.4Si) .delta. ppm
5.59 (dd, J=15.3, 4.8 Hz, 1H), 5.50 (dd, J=15.4, 7.3 Hz, 1H),
5.30-5.45 (m, 2H), 4.01-4.14 (m, 2H), 2.63 (dd, J=18.3, 6.7 Hz,
1H), 2.34 (t, J=7.5 Hz, 2H), 1.99-2.53 (m, 7H), 1.62-1.78 (m, 2H),
1.16-1.57 (m, 8H), 0.81-1.00 (m, 3H), 0.87 and 0.89 (2s, 18H), 0.04
and 0.05 (2s, 12H)
REFERENCE EXAMPLE 14
[0275] 72
[0276] In a dry nitrogen atmosphere, 0.4 ml of pyridine was added
to 110 mg (0.189 mmol) of compound (12f) in 6.8 ml of acetonitrile,
which was cooled to 0.degree. C. 0.32 ml of hydrogen fluoride
pyridine complex was added thereto, and the mixture was warmed up
to room temperature and stirred for 4 hours at room temperature.
Reaction was terminated with 5 ml of saturated aqueous sodium
bicarbonate, 5 ml of ethyl acetate was added,
(NH.sub.4).sub.2SO.sub.4 was added until it was saturated, and
extraction was done. The aqueous layer was further extracted with 5
ml of ethyl acetate. The organic layer was dried over magnesium
sulfate, concentrated, filtered through a silica gel pad, and then
concentrated. It was purified by silica gel column chromatography,
obtaining 61 mg of compound (13f). The yield was 92%. Analytical
data of compound (13f) was identical with compound (10c).
* * * * *