U.S. patent application number 10/586204 was filed with the patent office on 2008-11-13 for process for the production of asymmetric transformation catalysts.
This patent application is currently assigned to PHOENIX CHEMICALS LIMITED. Invention is credited to Wei-Ping Chen, John Whittall.
Application Number | 20080281106 10/586204 |
Document ID | / |
Family ID | 31726125 |
Filed Date | 2008-11-13 |
United States Patent
Application |
20080281106 |
Kind Code |
A1 |
Chen; Wei-Ping ; et
al. |
November 13, 2008 |
Process for the Production of Asymmetric Transformation
Catalysts
Abstract
The present invention relates to process for the production of
chiral ligands comprising providing a starting material of Formula
(A): wherein X* is a chiral or achiral directing group; and (i) is
an optionally substituted mono- or polycyclic aryl or cycloalkyl
group; ortholithiating the substrate; converting the
ortho-lithiated substrate to a phosphine group having the formula
--PR.sup.1R.sup.1'', R.sup.1 being selected from substituted and
unsubstituted, branched- and straight-chain alkyl, substituted and
unsubstituted cycloalkyl, substituted and unsubstituted carbocyclic
aryl, and substituted and unsubstituted heteroaryl wherein the or
each heteroatom is independently selected from sulphur, nitrogen,
and oxygen, R.sup.1'' being different from R.sup.1 and being
selected from substituted and unsubstituted, branched- and
straight-chain alkyl, substituted and unsubstituted cycloalkyl,
substituted and unsubstituted carbocyclic aryl, and substituted and
unsubstituted heteroaryl wherein the or each heteroatom is
independently selected from sulphur, nitrogen, and oxygen; and
optionally or if necessary converting X* to a different grouping to
produce a chiral ligand. ##STR00001##
Inventors: |
Chen; Wei-Ping; (Liverpool,
GB) ; Whittall; John; (Lancaster, GB) |
Correspondence
Address: |
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET, FOURTEENTH FLOOR
IRVINE
CA
92614
US
|
Assignee: |
PHOENIX CHEMICALS LIMITED
Bormborough, Wirral
GB
|
Family ID: |
31726125 |
Appl. No.: |
10/586204 |
Filed: |
January 14, 2005 |
PCT Filed: |
January 14, 2005 |
PCT NO: |
PCT/GB2005/000125 |
371 Date: |
September 29, 2006 |
Current U.S.
Class: |
548/101 ;
549/206; 556/20 |
Current CPC
Class: |
B01J 31/2295 20130101;
B01J 31/2452 20130101; B01J 31/189 20130101; B01J 2531/842
20130101; B01J 31/1845 20130101; B01J 2531/847 20130101; B01J
31/2409 20130101; C07F 17/02 20130101; B01J 31/188 20130101; B01J
31/2404 20130101; B01J 2531/82 20130101; B01J 2231/645 20130101;
B01J 31/2457 20130101; B01J 2531/0205 20130101; B01J 2531/822
20130101; B01J 31/1895 20130101; B01J 31/186 20130101; B01J 31/2495
20130101 |
Class at
Publication: |
548/101 ; 556/20;
549/206 |
International
Class: |
C07F 9/46 20060101
C07F009/46; C07F 15/00 20060101 C07F015/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 14, 2004 |
GB |
0400720.9 |
Claims
1-13. (canceled)
14. A process for the production of chiral ligands comprising:
providing a starting material of Formula (A): ##STR00112## wherein
X* is a chiral or achiral directing group; and wherein ##STR00113##
is selected from the group consisting of an unsubstituted mono-aryl
group, an unsubstituted polycyclic aryl group, an unsubstituted
cycloalkyl group, a substituted mono-aryl group, a substituted
polycyclic aryl group, and a substituted cycloalkyl group;
ortho-lithiating the substrate; converting the ortho-lithiated
substrate to include a phosphine group having the formula
--PR.sup.1R.sup.1'', wherein R.sup.1 and R.sup.1'' are different
from each other and are independently selected from the group
consisting of substituted branched-chain alkyl, substituted
straight-chain alkyl, substituted alkoxy, substituted alkylamino,
substituted cycloalkyl, substituted cycloalkoxy, substituted
cycloalkylamino, substituted carbocyclic aryl, substituted
carbocyclic aryloxy, substituted heteroaryl, substituted
heteroaryloxy, substituted carbocyclic arylamino, and substituted
heteroarylamino, unsubstituted branched-chain alkyl, unsubstituted
straight-chain alkyl, unsubstituted alkoxy, unsubstituted
alkylamino, unsubstituted cycloalkyl, unsubstituted cycloalkoxy,
unsubstituted cycloalkylamino, unsubstituted carbocyclic aryl,
unsubstituted carbocyclic aryloxy, unsubstituted heteroaryl,
unsubstituted heteroaryloxy, unsubstituted carbocyclic arylamino,
and unsubstituted heteroarylamino; and converting X* to a different
grouping to produce a chiral ligand.
15. The process according to claim 14, wherein X* is a chiral
directing group and the step of ortho-lithiating is
enantioselective.
16. A process according to claim 15, wherein X* is selected from
the group consisting of ##STR00114## wherein R, R.sup.2, and
R.sup.3 are independently selected from the group consisting of
unsubstituted branched-chain alkyl, unsubstituted straight-chain
alkyl, unsubstituted cycloalkyl, unsubstituted carbocyclic aryl,
unsubstituted heteroaryl, substituted branched-chain alkyl,
substituted straight-chain alkyl, substituted cycloalkyl,
substituted carbocyclic aryl, and substituted heteroaryl.
17. The process according to claim 14, wherein X* is an achiral
directing group and wherein ortho-lithiating is conducted in the
presence of a chiral auxiliary and is enantioselective.
18. The process according to claim 17, wherein X* is selected from
the group consisting of ##STR00115## and wherein R.sup.2 and
R.sup.3 are independently selected from the group consisting of
unsubstituted branched-chain alkyl, unsubstituted straight-chain
alkyl, unsubstituted cycloalkyl, unsubstituted carbocyclic aryl,
unsubstituted heteroaryl, substituted branched-chain alkyl,
substituted straight-chain alkyl substituted cycloalkyl,
substituted carbocyclic aryl, and substituted heteroaryl.
19. The process according to claim 14, wherein ##STR00116## is a
substituted or unsubstituted aromatic ring of a metallocene
compound.
20. The process according to claim 14, wherein X* is an ortho
directing group.
21. The process according to claim 14, further comprising the step
of reacting the ortho-lithiated substrate with an R.sup.1
substituted phosphine or an R.sup.1 substituted arsine to form an
intermediate compound.
22. The process according to claim 21, comprising reacting the
intermediate compound with an R.sup.1''-bearing Grignard reagent or
organolithium compound.
23. A chiral ligand produced by the process according to claim
14.
24. A transition metal complex catalyst comprising at least one
chiral ligand produced according to the process of claim 14.
25. An asymmetric catalyst comprising the transition metal complex
catalyst of claim 24.
26. A process for the production of chiral ligands comprising:
providing a starting material of Formula (A): ##STR00117## wherein
X* is a chiral or achiral directing group; and wherein ##STR00118##
is selected from the group consisting of an unsubstituted mono-aryl
group, an unsubstituted polycyclic aryl group, an unsubstituted
cycloalkyl group, a substituted mono-aryl group, a substituted
polycyclic aryl group, and a substituted cycloalkyl group;
ortho-lithiating the substrate; converting the ortho-lithiated
substrate to a chiral ligand comprising a phosphine group having
the formula --PR.sup.1R.sup.1'', wherein R.sup.1 and R.sup.1'' are
different from each other and are independently selected from the
group consisting of substituted branched-chain alkyl, substituted
straight-chain alkyl, substituted alkoxy, substituted alkylamino,
substituted cycloalkyl, substituted cycloalkoxy, substituted
cycloalkylamino, substituted carbocyclic aryl, substituted
carbocyclic aryloxy, substituted heteroaryl, substituted
heteroaryloxy, substituted carbocyclic arylamino, and substituted
heteroarylamino, unsubstituted branched-chain alkyl, unsubstituted
straight-chain alkyl, unsubstituted alkoxy, unsubstituted
alkylamino, unsubstituted cycloalkyl, unsubstituted cycloalkoxy,
unsubstituted cycloalkylamino, unsubstituted carbocyclic aryl,
unsubstituted carbocyclic aryloxy, unsubstituted heteroaryl,
unsubstituted heteroaryloxy, unsubstituted carbocyclic arylamino,
and unsubstituted heteroarylamino.
27. The process according to claim 26, wherein X* is a chiral
directing group and the step of ortho-lithiating is
enantioselective.
28. A process according to claim 27, wherein X* is selected from
the group consisting of ##STR00119## wherein R, R.sup.2, and
R.sup.3 are independently selected from the group consisting of
unsubstituted branched-chain alkyl, unsubstituted straight-chain
alkyl, unsubstituted cycloalkyl, unsubstituted carbocyclic aryl,
unsubstituted heteroaryl, substituted branched-chain alkyl,
substituted straight-chain alkyl, substituted cycloalkyl,
substituted carbocyclic aryl, and substituted heteroaryl.
29. The process according to claim 26, wherein X* is an achiral
directing group and wherein ortho-lithiating is conducted in the
presence of a chiral auxiliary and is enantioselective.
30. The process according to claim 29, wherein X* is selected from
the group consisting of ##STR00120## and wherein R.sup.2 and
R.sup.3 are independently selected from the group consisting of
unsubstituted branched-chain alkyl, unsubstituted straight-chain
alkyl, unsubstituted cycloalkyl, unsubstituted carbocyclic aryl,
unsubstituted heteroaryl, substituted branched-chain alkyl,
substituted straight-chain alkyl, substituted cycloalkyl,
substituted carbocyclic aryl, and substituted heteroaryl.
31. The process according to claim 26, wherein ##STR00121## is a
substituted or unsubstituted aromatic ring of a metallocene
compound.
32. The process according to claim 26, wherein X* is an ortho
directing group.
33. The process according to claim 26, further comprising the step
of reacting the ortho-lithiated substrate with an R.sup.1
substituted phosphine or an R.sup.1 substituted arsine to form an
intermediate compound.
34. The process according to claim 33, comprising reacting the
intermediate compound with an R.sup.1''-bearing Grignard reagent or
organolithium compound.
35. A chiral ligand produced by the process according to claim
26.
37. A transition metal complex catalyst comprising at least one
chiral ligand produced according to the process of claim 26.
38. An asymmetric catalyst comprising the transition metal complex
catalyst of claim 37.
Description
[0001] This invention relates to a novel process for the production
of asymmetric transformation catalysts, in particular to such a
process for the production of phosphine and arsine ligands having a
chiral centre at phosphorus, or arsenic as the case may be. Such
ligands are found to be useful in a wide variety of asymmetric
transformation reactions, including hydrogenation and carbon-oxygen
and carbon-nitrogen bond formation reactions. The process of the
invention may be applicable to the production of chiral catalysts
containing aromatic ring systems generally, and is especially
useful in the production of metallocene-based phosphine and arsine
ligands. The invention also relates to chiral catalysts produced by
the process of the invention, and to the use of such catalysts in
asymmetric transformation reactions.
[0002] Ferrocene as a backbone for diphosphine ligands was
introduced by Kumada and Hayashi based on the pioneering work of
Ugi related to the synthesis of enantiopure substituted
metallocenes.sup.1. A number of these ligands are shown below:
##STR00002##
[0003] Ppfa as well as bppfa and bppfoh proved to be effective
ligands for the catalysis of a variety of asymmetric
transformations. From this starting point, many chiral
ferrocene-based bisphosphine ligands with a range of structural
variation have been developed in the last few years.
[0004] Certain types of known ligands exhibit both planar and
carbon chirality:
##STR00003##
[0005] Togni and Spindler.sup.2 have reported a class of
non-C.sub.2-symmetrical ferrocene-based bisphosphines: the
Josiphos-type ligands. Josiphos ligands are in widespread
commercial use, having been found effective for Rh-catalyzed
hydrogenation of .alpha.-acetamidocinnamate, dimethyl itaconate,
and .beta.-ketoesters. Because the two phosphine groups are
introduced into the ligand in consecutive steps with high yields, a
variety of ligands are available with widely differing steric and
electronic properties. The ligands have already been applied in
three production processes.sup.3, several pilot processes and many
other syntheses. For example, PPF-tBu2, a Josiphos type ligand with
a di-(tert-butyl)phosphino group, has been applied as the ligand in
asymmetric hydrogenation for commercial synthesis of
(+)-biotin..sup.4 Another notable example is the application of
XyliPhos in the Ir-catalyzed hydrogenation of imines for the
synthesis of the herbicide (S)-metolachlor.sup.5.
[0006] Bophoz.sup.6 is a combination of a phosphine and an
aminophosphine and is prepared in 3 steps from ppfa with high
overall yields. The ligand is air stable and effective for the
hydrogenation of enamides, itaconates and .alpha.-keto acid
derivatives. As observed for several ligands forming seven-membered
chelates, high activities can be reached and TONs up to 10,000 have
been claimed. The full scope of this modular ligand class has not
yet been explored.
[0007] A class of non-C.sub.2-symmetrical, ferrocene-based
1,5-diphosphine ligands, Taniaphos, has been developed by
Knochel.sup.7,8. Compared to the Josiphos ligands, Taniaphos has an
additional phenyl ring inserted at the side chain of the Ugi amine.
Taniaphos gave excellent results in Rh and Ru-catalyzed asymmetric
hydrogenation. The configuration of .alpha.-position of Taniaphos
plays an important role in the enantioselectivities and activities.
The Taniaphos 1b with aS configuration leads to higher
enantioselectivities and activities than 1a with aR configuration
in a wide range of asymmetric transformations.
[0008] Weissensteiner and Spindler.sup.9 have reported a series of
structurally different ferrocene-based 1,5-diphosphine ligands,
Walphos. Like Josiphos, Walphos is modular and is also made from
the Ugi amine. It shows promise for the enantioselective
hydrogenation of olefins and ketones.
[0009] Mandyphos is a bidentate version of ppfa with C.sub.2
symmetry, where in addition to the PPh.sub.2 moieties, R and R' can
be used for fine tuning the functionality of the ligand.sup.10. The
scope of this ligand family has not yet been fully explored, but
preliminary results indicate high enantioselectivities for the
Rh-catalyzed hydrogenation of enamides, itaconates and enol
acetates.
[0010] The TRAP ligands developed by Ito.sup.11 form 9-membered
metallocycles. However, it is not clear whether the cis-isomer,
present in small amounts, or the major trans-isomer is responsible
for the catalytic activity. Up to now only a few different PR2
fragments have been tested, but it is clear that the choice of R
strongly affects the catalytic performance. The Rh complexes work
best at very low pressures of 0.5.+-.1 bar and effectively reduces
indole-derivatives, enamides and itaconic acid derivatives.
[0011] Another class of known ligands exhibit only planar
chirality:
##STR00004##
[0012] Kang.sup.12 reported the C2-symmetry FerroPHOS with only
planar chirality. FerroPHOS ligands are air-stable and are very
efficient for the asymmetric hydrogenation of various dehydroamino
acid derivitives (up to 99% ee).
[0013] Another C.sub.2-symmetry planar chiral diphosphine,
JAFAPhos, has been developed by Jendralla.sup.13. JAFAPhos gave
excellent results in asymmetric hydrogenation, allylic alkylation,
Grignard cross coupling and aldol reactions.
[0014] Kagan.sup.14 reported plane chiral ferrocene-based
bisphosphorus ligands 2 and 3, and up to 95% ee's have been
obtained in asymmetric hydrogenation of dimethyl itaconate using
these ligands as catalyst.
[0015] Another class of known diphosphine ligands exhibit chirality
only at the phosphorus atoms:
##STR00005##
[0016] The synthesis of chiral 1,1'-bis(phosphetano) ferrocenes
(FerroTANE) has been independently reported by Marinetti.sup.15 and
Burk.sup.16. FerroTANE has been successfully applied in
Rh-catalyzed hydrogenation of itaconates and
(E)-.beta.-(acylamino)acrylates.sup.17.
[0017] Mezzetti.sup.18 and van Leeuwen.sup.19 have independently
reported P-chiral ferrocenyl bisphosphines 4a and 4b. These two
ligands have shown excellent enantioselectivities (up to 99% ee)
for asymmetric hydrogenation of .alpha.-dehydroamino acid
derivatives.
[0018] Zhang has reported a 1,1'-bis(Phospholanyl) ferrocene ligand
5 with ketal substitutes at the 3 and 4 positions..sup.20 The
ligand has shown excellent enantioselectivities in hydrogenation of
.beta.-dehydroamino acid derivatives. The ketal groups of the
ligand are important for achieving the high enantioselectivity,
since the corresponding ligand without ketal groups only provides
moderate ee's. Zhang has also developed a
1,1'-bis(dinaphthophosphepinyl)ferrocene ligand, f-binaphane, which
has been successfully applied in the Ir-catalyzed hydrogenation of
acyclic aryl imines..sup.21
[0019] Reetz has developed a binaphthol-derived ferrocene-based
bisphosphonite ligand 622, which has shown excellent reactivities
and enantioselectivities in Rh-catalyzed hydrogenation of
itaconates and a-dehydroamino acid derivatives.
[0020] Another class of known ligands exhibits both planar and
phosphorus chirality:
##STR00006##
[0021] Van Leeuwen has reported ferrocene-based bisphosphines
combining planar and phosphorus chirality 7a and 7b.sup.23. These
two ligands have shown excellent enantioselectivities (up to 99%
ee) for asymmetric allylic alkylations.
[0022] Thus, most of the known ferrocene-based diphosphines contain
planar and carbon chirality, only planar chirality or only
phosphorus chirality. More recently, Togni reported the first
tridentate ferrocene-based phosphine ligand 12 combining planar,
phosphorus and carbon chirality..sup.24
##STR00007##
[0023] In our co-pending application GB0400720.9 we describe
ligands having Formula (I), (II) or (III):
##STR00008##
wherein R.sup.1-5, W, Q, n, m and G are variously defined, and a
process for making such ligands. However, the process described
therein is found to be more generally applicable to the production
of various chiral ligands.
[0024] According to the present invention there is provided a
process for the production of chiral ligands comprising providing a
starting material of Formula (A):
##STR00009##
wherein X* is a chiral or achiral directing group; and
##STR00010##
is an optionally substituted mono- or polycyclic aryl or cycloalkyl
group; ortholithiating the substrate; converting the
ortho-lithiated substrate to a phosphine group having the formula
--PR.sup.1, R.sup.1'', R.sup.1 and R.sup.1'' being different from
each other and independently selected from substituted and
unsubstituted, branched- and straight-chain alkyl, alkoxy,
alkylamino, substituted and unsubstituted cycloalkyl, substituted
and unsubstituted cycloalkoxy, substituted and unsubstituted
cycloalkylamino, substituted and unsubstituted carbocyclic aryl,
substituted and unsubstituted carbocyclic aryloxy, substituted and
unsubstituted heteroaryl, substituted and unsubstituted
heteroaryloxy, substituted and unsubstituted carbocyclic arylamino
and substituted and unsubstituted heteroarylamino, wherein the or
each heteroatom is independently selected from sulphur, nitrogen,
and oxygen; and optionally or if necessary converting X* to a
different grouping to produce a chiral ligand.
##STR00011##
is, in one such process according to the invention, one aromatic
ring (optionally further substituted) of a metallocene
compound.
[0025] Also provided in accordance with the invention is a process
for the production of chiral ligands comprising providing a
starting material of Formula (A):
##STR00012##
wherein X* is a chiral or achiral directing group; and
##STR00013##
is an optionally substituted mono- or polycyclic aryl or cycloalkyl
group; ortholithiating the substrate; reacting the ortholithiated
substrate with an R.sup.1 substituted phosphine or arsine, R.sup.1
being selected from substituted and unsubstituted, branched- and
straight-chain alkyl, substituted and unsubstituted cycloalkyl,
substituted and unsubstituted carbocyclic aryl, and substituted and
unsubstituted heteroaryl wherein the or each heteroatom is
independently selected from sulphur, nitrogen, and oxygen; and then
with an R.sup.1''-bearing Grignard reagent or organolithium
compound, R.sup.1'' being different from R.sup.1 and being selected
from substituted and unsubstituted, branched- and straight-chain
alkyl, substituted and unsubstituted cycloalkyl, substituted and
unsubstituted carbocyclic aryl, and substituted and unsubstituted
heteroaryl wherein the or each heteroatom is independently selected
from sulphur, nitrogen, and oxygen; and optionally or if necessary
converting X* to a different grouping to produce a chiral ligand;
with the exception that the chiral ligand is not a ligand having
Formula (I), (II) or (III):
##STR00014##
wherein R.sup.1-5, W, Q, n, m and G are as defined in
GB0400720.9.
##STR00015##
is, in one such process according to the invention, one aromatic
ring (optionally further substituted) of a metallocene
compound.
[0026] The process of the invention may be used in the production
of phosphine or arsine ligands having up to three elements of
chirality; planar chirality, chirality at phosphorus (or arsenic),
and optionally chirality at carbon.
[0027] In the following description reference will be made for
convenience to processes for the production of phosphine ligands.
It should be understood that although processes for producing
phosphine ligands are the preferred processes in accordance with
the invention, the corresponding processes for producing arsine
ligands are also within the scope of the invention.
[0028] Similarly, when the chiral ligand obtained by the process of
the invention is a metallocene ligand, processes for producing
ferrocene based ligands are preferred, but other suitable metals
may be used in the metallocene ligands obtained by the process of
the invention, and hence reference is made herein to metallocenes
generally.
[0029] The invention further provides chiral ligands obtained by
the process of the invention. Examples of such ligands include
metallocene-based phosphine ligands having planar, phosphorus and
carbon chirality.
[0030] The invention further provides chiral ligands (other than
those of Formula (I), (II) or (III)) obtained by the process of the
invention. Examples of such ligands include metallocene-based
phosphine ligands having planar, phosphorus and carbon
chirality.
[0031] Ligands obtained by a process according to the invention
have particular advantages over prior art ligands because the
provision of up to three chiralities allows the designer of a
ligand greater scope than has hitherto been the case to design
ligands for a particular purpose.
[0032] The introduction of phosphorus chirality may enhance the
chiral discrimination produced by the catalyst when a matching
among the planar chirality, carbon chirality and the chirality of
phosphorus can be achieved. A matching catalyst may give high ee
and a mismatching one may give low ee.
[0033] Also provided in accordance with the invention is a
transition metal complex containing transition metal coordinated to
the ligand produced by the process of the invention. The metal is
preferably a Group VIb or a Group VIII metal.
[0034] Preferably X* is an ortho directing group.
[0035] Synthesis of phosphorus chiral phosphines may be effected in
accordance with the invention with the use of a suitable chiral
ortho-directing group, for example in accordance with the following
scheme:
##STR00016##
[0036] Wherein
##STR00017##
is an optionally substituted mono- or polycyclic aryl or cycloalkyl
group and wherein R.sup.1''Z is an organoalkali species or Grignard
reagent
[0037] Examples of suitable chiral directing groups:
##STR00018##
[0038] Wherein R, R.sup.2 and R.sup.3 are independently selected
from substituted and unsubstituted, branched- and straight-chain
alkyl, substituted and unsubstituted cycloalkyl, substituted and
unsubstituted carbocyclic aryl, and substituted and unsubstituted
heteroaryl wherein the or each heteroatom is independently selected
from sulphur, nitrogen, and oxygen.
##STR00019##
is, in one such process according to the invention, one aromatic
ring (optionally further substituted) of a metallocene compound.
and wherein
[0039] For example, synthesis of ferrocene-based phosphorus chiral
phosphines may be effected with the use of a suitable chiral
ortho-directing group, for example in accordance with the following
schemes:
##STR00020##
[0040] Examples of suitable chiral directing groups are as
previously specified.
wherein, in relation to scheme 3, L is a linker. For example, L may
be selected from ferrocene, diphenyl ethers, xanthenes,
2,3-benzothiophene, 1,2-benzene, succinimides and many others.
Conveniently, such dianionic linkers may be made from a
corresponding di-halo precursor, eg:
[0041] Certain suitable dianionic linkers may be represented as
follows:
[0042] However, ferrocene is a preferred linker in accordance with
the invention.
(Similar schemes may be used to synthesise the corresponding
arsines, and other metallocenes, and may be applicable to other
ring systems. Also, for convenience, these schemes are depicted
with ferrocene-based substrates, but they may be also be applicable
to other aromatic-based substrates.)
[0043] Accordingly, the invention provides a method for preparing a
phosphine ligand chiral at phosphorus comprising providing an
optionally substituted mono- or polyaromatic or cycloalkyl
substrate having a chiral or achiral directing substituent on at
least one ring, and subjecting the substrate to an ortho-lithiation
step before subsequently converting the ortho-lithiated substrate
to a phosphine group having the formula --PR.sup.1R.sup.1'' or
PR.sup.1L, wherein L is a linker as previously defined and wherein,
R.sup.1 and R.sup.1'' are different from each other and are
independently selected from substituted and unsubstituted,
branched- and straight-chain alkyl, substituted and unsubstituted
cycloalkyl, substituted and unsubstituted carbocyclic aryl, and
substituted and unsubstituted heteroaryl wherein the or each
heteroatom is independently selected from sulphur, nitrogen, and
oxygen, and optionally or if necessary converting the directing
substituent to a chiral group, or to a different chiral group.
[0044] Accordingly, the invention provides a method for preparing a
phosphine ligand chiral at phosphorus comprising providing a
metallocene-based substrate having a chiral or achiral directing
substituent on at least one ring, and subjecting the substituted
metallocene to an ortho-lithiation step before subsequently
converting the ortho-lithiated substrate to a phosphine group
having the formula --PR.sup.1R.sup.1'' or PR.sup.1L, wherein L is a
linker as previously defined and wherein, R.sup.1 and R.sup.1'' are
different from each other and are independently selected from
substituted and unsubstituted, branched- and straight-chain alkyl,
substituted and unsubstituted cycloalkyl, substituted and
unsubstituted carbocyclic aryl, and substituted and unsubstituted
heteroaryl wherein the or each heteroatom is independently selected
from sulphur, nitrogen, and oxygen, and optionally or if necessary
converting the directing substituent to a chiral group, or to a
different chiral group.
[0045] The invention also provides a method for preparing an arsine
ligand chiral at arsenic comprising providing an optionally
substituted mono- or polyaromatic or cycloalkyl substrate having a
chiral or achiral directing substituent on at least one ring, and
subjecting the substrate to an ortho-lithiation step before
subsequently converting the ortho-lithiated substrate to an arsine
group having the formula --AsR.sup.1R.sup.1'' or AsR.sup.1L,
wherein L is a linker as previously defined and wherein, R.sup.1
and R.sup.1'' are different from each other and are independently
selected from substituted and unsubstituted, branched- and
straight-chain alkyl, substituted and unsubstituted cycloalkyl,
substituted and unsubstituted carbocyclic aryl, and substituted and
unsubstituted heteroaryl wherein the or each heteroatom is
independently selected from sulphur, nitrogen, and oxygen, and
optionally or if necessary converting the directing substituent to
a chiral group, or to a different chiral group.
[0046] The invention also provides a method for preparing an arsine
ligand chiral at arsenic comprising providing a metallocene-based
substrate having a chiral or achiral directing substituent on at
least one ring, and subjecting the substituted metallocene to an
ortho-lithiation step before subsequently converting the
ortho-lithiated substrate to an arsine group having the formula
--AsR.sup.1R.sup.1'' or AsR.sup.1L, wherein L is a linker as
previously defined and wherein, R.sup.1 and R.sup.1'' are
independently selected from substituted and unsubstituted,
branched- and straight-chain alkyl, substituted and unsubstituted
cycloalkyl, substituted and unsubstituted carbocyclic aryl, and
substituted and unsubstituted heteroaryl wherein the or each
heteroatom is independently selected from sulphur, nitrogen, and
oxygen, and optionally or if necessary converting the directing
substituent to a chiral group, or to a different chiral group.
[0047] Methods in accordance with the invention for the preparation
of chiral ligands will now be more particularly described.
[0048] For example, one such method comprises providing a substrate
of the Formula (A):
##STR00021##
wherein
##STR00022##
is an optionally substituted mono- or polycyclic aryl or cycloalkyl
group; X* is chiral directing group, and is preferably selected
from the group as previously defined; ortholithiating the
substrate; reacting the ortholithiated substrate with an R.sup.1
substituted halophosphine or haloarsine, R.sup.1 being selected
from substituted and unsubstituted, branched- and straight-chain
alkyl, substituted and unsubstituted cycloalkyl, substituted and
unsubstituted carbocyclic aryl, and substituted and unsubstituted
heteroaryl wherein the or each heteroatom is independently selected
from sulphur, nitrogen, and oxygen; and then with an
R.sup.1''-bearing Grignard reagent or organoalkali (preferably
organolithium) compound, R.sup.1'' being dfferent from R.sup.1 and
being selected from substituted and unsubstituted, branched- and
straight-chain alkyl, substituted and unsubstituted cycloalkyl,
substituted and unsubstituted carbocyclic aryl, and substituted and
unsubstituted heteroaryl wherein the or each heteroatom is
independently selected from sulphur, nitrogen, and oxygen; and
optionally converting X* to a different grouping to produce a
chiral ligand.
##STR00023##
is, in one such process according to the invention, one aromatic
ring (optionally further substituted) of a metallocene
compound.
[0049] Another method comprises providing a compound of the Formula
(A):
##STR00024##
wherein
##STR00025##
is optionally substituted mono- or polycyclic aryl or cycloalkyl
group; X* is chiral directing group, and is preferably selected
from the group as previously defined; ortholithiating the
substrate; reacting the ortholithiated substrate with an R.sup.1
substituted halophosphine or haloarsine, R.sup.1 being selected
from substituted and unsubstituted, branched- and straight-chain
alkyl, substituted and unsubstituted cycloalkyl, substituted and
unsubstituted carbocyclic aryl, and substituted and unsubstituted
heteroaryl wherein the or each heteroatom is independently selected
from sulphur, nitrogen, and oxygen; and then with an
R.sup.1''-bearing Grignard reagent or organoalkali (preferably
organolithium) compound, R.sup.1'' being selected from substituted
and unsubstituted, branched- and straight-chain alkyl, substituted
and unsubstituted cycloalkyl, substituted and unsubstituted
carbocyclic aryl, and substituted and unsubstituted heteroaryl
wherein the or each heteroatom is independently selected from
sulphur, nitrogen, and oxygen; and optionally converting X* to a
different grouping to produce a chiral ligand; with the exception
that the chiral ligand is not a ligand having Formula (I), (II) or
(III):
##STR00026##
wherein R.sup.1-5, W, Q, n, m and G are as defined in
GB0400720.9.
##STR00027##
is, in one such process according to the invention, one aromatic
ring (optionally further substituted) of a metallocene
compound.
[0050] One particularly preferred X* group in each of the above
methods is
##STR00028##
[0051] The ortho-lithiation step is preferably a
mono-ortho-lithiation step using n-butyllithium, sec-butyllithium
or tert-butyllithium. The resulting monolithium compound is
preferably reacted in situ with a dichlorophosphine of the formula
R.sup.1PCl.sub.2 followed by reacting with an organometallic
reagent of the formula R.sup.1''Z, wherein R.sup.1 and R.sup.1''
are as defined above; Z is Li or MgY wherein Y is a halide.
[0052] These steps may be performed to obtain a phosphorus chiral
compound having formula (C) (wherein the aromatic or cycloaliphatic
ring(s) is/are optionally substituted:
##STR00029##
[0053] The synthesis preferably proceeds by converting compound (C)
to compound D, E, or F:
##STR00030##
wherein R.sup.d is an acyl group, R.sup.e is selected from
hydrogen, substituted and unsubstituted, branched- and
straight-chain alkyl, substituted and unsubstituted cycloalkyl,
substituted and unsubstituted carbocyclic aryl, and substituted and
unsubstituted heteroaryl wherein the or each heteroatom is
independently selected from sulphur, nitrogen, and oxygen, and
R.sup.1, R.sup.1'' are as previously defined; and then: reacting
compound D with a secondary phosphine of the formula
R.sup.6R.sup.7PH wherein R.sup.6 and R.sup.7 are the same or
different, and are independently selected from substituted and
unsubstituted, branched- and straight-chain alkyl, alkoxy,
alkylamino, substituted and unsubstituted cycloalkyl, substituted
and unsubstituted cycloalkoxy, substituted and unsubstituted
cycloalkylamino, substituted and unsubstituted carbocyclic aryl,
substituted and unsubstituted carbocyclic aryloxy, substituted and
unsubstituted heteroaryl, substituted and unsubstituted
heteroaryloxy, substituted and unsubstituted carbocyclic arylamino
and substituted and unsubstituted heteroarylamino, wherein the or
each heteroatom is independently selected from sulphur, nitrogen,
and oxygen; and R.sup.8 is selected from hydrogen, substituted and
unsubstituted, branched- and straight-chain alkyl, substituted and
unsubstituted cycloalkyl, substituted and unsubstituted carbocyclic
aryl, and substituted and unsubstituted heteroaryl wherein the or
each heteroatom is independently selected from sulphur, nitrogen,
and oxygen to obtain the diphosphine combining planar, phosphorus
and carbon chirality having formula G:
##STR00031##
or; reacting compound D with an amine of the formula
R.sup.8NH.sub.2 wherein R.sup.8 is selected from hydrogen,
substituted and unsubstituted, branched- and straight-chain alkyl,
substituted and unsubstituted cycloalkyl, substituted and
unsubstituted carbocyclic aryl, and substituted and unsubstituted
heteroaryl wherein the or each heteroatom is independently selected
from sulphur, nitrogen, and oxygen, to obtain compound H:
##STR00032##
or; reacting compound D with an amine of the formula J:
##STR00033##
wherein R.sup.6 and R.sup.7 are as previously defined, R.sup.9 is
selected from hydrogen, halogen, OR.sup.10, SR.sup.10,
NR.sup.10R.sup.11, substituted and unsubstituted, branched- and
straight-chain alkyl, substituted and unsubstituted cycloalkyl,
substituted and unsubstituted carbocyclic aryl, and substituted and
unsubstituted heteroaryl wherein the or each heteroatom is
independently selected from sulphur, nitrogen, and oxygen; wherein
R.sup.10, R.sup.11 are the same or different and are independently
selected from hydrogen, substituted and unsubstituted, branched-
and straight-chain alkyl, substituted and unsubstituted cycloalkyl,
substituted and unsubstituted carbocyclic aryl, and substituted and
unsubstituted heteroaryl wherein the or each heteroatom is
independently selected from sulphur, nitrogen, and oxygen, n' is 0
to 4, and Z is MgY (Y being a halide) or Li, to obtain compound
K:
##STR00034##
or; reacting compound D with an amine of the formula
H.sub.2N--R*--NH.sub.2 or H.sub.2N--R**--NH.sub.2 wherein R* and
R** are selected from the group consisting of:
##STR00035##
wherein R.sup.9 is as previously defined; R.sup.12 is selected from
hydrogen, substituted and unsubstituted, branched- and
straight-chain alkyl, substituted and unsubstituted cycloalkyl,
substituted and unsubstituted carbocyclic aryl, and substituted and
unsubstituted heteroaryl wherein the or each heteroatom is
independently selected from sulphur, nitrogen, and oxygen; or
(R.sup.12).sub.2 is --(CH.sub.2).sub.m--, n' is 0 to 4; and m' is 1
to 8, to obtain compounds L and M:
##STR00036##
or; reacting compound E with an amine of the formula
H.sub.2N--R*--NH.sub.2 or H.sub.2N--R**--NH.sub.2 wherein R* and
R** are, as previously defined, to obtain compounds O and P:
##STR00037##
[0054] Compound H may be reacted with a halophosphine of the
formula R.sup.6R.sup.7PY wherein R.sup.6, R.sup.7 are, as
previously defined, and Y is chlorine, bromine or iodine, to obtain
compound Q:
##STR00038##
[0055] Alternatively, compound H may be reacted with an acid
derivative of the formula R.sup.13COY wherein R.sup.13 is selected
from hydrogen, substituted and unsubstituted, branched- and
straight-chain alkyl, substituted and unsubstituted cycloalkyl,
substituted and unsubstituted carbocyclic aryl, and substituted and
unsubstituted heteroaryl wherein the or each heteroatom is
independently selected from sulphur, nitrogen, and oxygen, and Y is
a halide, a sulphate, an imidazole, R.sup.13COO-- or hydrogen, to
obtain compound R:
##STR00039##
[0056] Alternatively compound H (in which R.sup.8 is hydrogen) may
be reacted with an aldehyde of the formula OHC--R*--CHO or
OHC--R**--CHO wherein R* and R are as previously defined to obtain
the compounds having Formulae S and T:
##STR00040##
[0057] Alternatively compound H may be reacted with an acid
derivative of the formula YOC--R*--COY and YOC--R**--COY wherein
R*, R** and Y are, as previously defined, to obtain the compounds
having Formulae U and V:
##STR00041##
Compound K may be converted into compound X:
##STR00042##
wherein R.sup.14 is selected from OR.sup.10, SR.sup.10, NHR.sup.10
and NR.sup.10R.sup.11, wherein R.sup.10, R.sup.11 are as previously
defined.
[0058] Compounds L, M, O, P, S, T, U, V may be reduced to obtain
respective compounds L*, M*, O*, P*, S*, T*, U*, V*:
##STR00043## ##STR00044##
[0059] Synthesis of metallocene-based phosphines chiral at
phosphorus may be also effected with the use of enantioselective
ortho-lithiation (ferrocene-based substrates are indicated below
and are illustrative of aromatic and cycloaliphatic substrates
generally in connection with the process of the invention):
##STR00045##
[0060] Examples of suitable achiral directing groups:
##STR00046##
(wherein R.sup.2 and R.sup.3 are as previously defined)
[0061] Suitable Chiral diamines include:
##STR00047##
[0062] Accordingly, the invention provides a method for preparing a
chiral diphosphine ligand comprising a metallocene-based substrate
having an achiral directing substituent on one or both rings, and
subjecting the substituted metallocene to an enantioselective
ortho-lithiation step before subsequently converting the
ortho-lithiated substrate to a phosphorus chiral phosphine.
[0063] Whilst the use of an auxiliary chiral compound (such as the
chiral diamine) in the ortholithiation step may be preferred in
some circumstances, where direct synthesis of a chiral product (in
enantiomeric excess) is desired, it is also possible to
ortholithiate in the absence of such a chiral auxiliary, and then
resolve the enantiomeric product mixture at the end of the
synthesis.
(This Method is Also Applicable to Arsines.)
[0064] Thus, one method according to the present invention for
preparing chiral ligands comprises providing a substrate of the
formula A*:
##STR00048##
wherein
##STR00049##
is an optionally substituted mono- or polycyclic aryl or cycloalkyl
group; wherein X** is an achiral directing group, and is preferably
as previously defined; and subjecting the compound to
enantioselective mono-ortho-lithiation using n-butyllithium or
sec-butyllithium or tert-butyllithium in the presence of a
homochiral tertiary amine, and reacting the resulting chiral
monolithium compound in situ with a dichlomphosphine of the formula
R.sup.1PCl.sub.2 followed by reacting with an organometallic
reagent of the formula R.sup.1''M, wherein R.sup.1 and R.sup.1''
are as defined hereinabove; M is Li or MgX wherein X is a halide,
to obtain phosphorus chiral compound having formula C*:
##STR00050##
and optionally or if necessary further converting compound C* to
the desired chiral ligand.
[0065] One method according to the invention for preparing a
ferrocene-based chiral ligand comprises providing a compound of the
Formula B*:
##STR00051##
wherein X* is as previously defined; and subjecting the compound to
bis-ortho-lithiation using n-butyllithium, sec-butyllithium or
tert-butyllithium, and reacting the resulting bislithium compound
in situ with a dichlorophosphine of the formula R.sup.1PCl.sub.2
followed by reacting with an organometallic reagent of the formula
R.sup.1''Z, wherein R.sup.1 and R.sup.1'' are as previously
defined; Z is Li or MgY wherein Y is a halide, to obtain a
phosphorus chiral compound having formula B***:
##STR00052##
and optionally or if necessary converting compound B*** to the
desired chiral ligand.
[0066] The invention will now be more particularly illustrated with
reference to the following Examples.
EXAMPLE 1
(R.sub.C,S.sub.Fe,S.sub.P)-2-[(1-N,N-Dimethylamino)ethyl]-1-[(2-methoxyphe-
nyl)phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-2]
##STR00053##
[0068] To a solution of (R)--N,N-dimethyl-1-ferrocenylethylamine
[(R)-Ugi's amine, (R)-1] (3.86 g, 15 mmol) in Et.sub.2O (50 mL) was
added 1.7 M t-BuLi solution in pentane (9.7 mL, 16.5 mmol) over 10
min via a syringe at -78.degree. C. After addition was completed,
the mixture was warmed to room temperature, and stirred for 1.5 h
at room temperature. The resulting red solution was cooled to
-78.degree. C. again, and dichlorophenylphosphine (2.24 mL, 16.5
mmol) was added in one portion. After stirring for 10 min at
-78.degree. C., the mixture was slowly warmed to room temperature,
and stirred for 1.5 h at room temperature. The mixture was then
cooled to -78.degree. C. again, and a solution of
(2-methoxy)phenyllithium [prepared from 2-bromoanisole (3.32 g,
17.7 mmol) and 1.7 M t-BuLi solution in pentane (20.8 mL, 35.4
mmol) in Et.sub.2O (90 mL) at -78.degree. C.] was added slowly via
a cannula. The mixture was warmed to room temperature overnight,
and filtered through a pad of Celite. The filtrate was
concentrated, and the residue was purified by chromatography
(SiO.sub.2, hexane-EtOAc-Et.sub.3N=85:10:5) to afford the title
compound (6.50 g, 92%) as orange crystals. .sup.1H NMR (CDCl.sub.3,
400.13 MHz): .delta. 1.29 (d, 3H, J=6.5 Hz); 1.80 (s, 6H); 3.91 (s,
3H); 3.97 (s, 6H, overlap); 4.11 (m, 1H), 4.25 (t, 1H, J=2.2 Hz);
4.37 (br. s, 1H); 6.87 (m, 1H); 6.94 (dd, 1H, J=8.3 and 6.7 Hz);
7.12.about.7.23 (m, 6H); 7.31 (m, 1H); .sup.31P NMR (CDCl.sub.3,
162 MHz): .delta. -38.82. The absolute configuration of
(R.sub.C,S.sub.Fe, S.sub.P)-2 was determined by single-crystal
X-ray diffraction analysis.
EXAMPLE 2
(R.sub.C,S.sub.Fe,S.sub.P)-2-[(1-N,N-Dimethylamino)ethyl]-1-[(1-naphthyl)p-
henylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-3]
##STR00054##
[0070] To a solution of (R)--N,N-dimethyl-1-ferrocenylethylamine
[(R)-Ugi's amine, (R)-1] (5.15 g, 20 mmol) in Et.sub.2O (60 mL) was
added 1.7 M t-BuLi solution in pentane (12.94 mL, 22 mmol) over 10
min via a syringe at -78.degree. C. After addition was completed,
the mixture was warmed to room temperature, and stirred for 1.5 h
at room temperature. The resulting red solution was cooled to
-78.degree. C. again, and dichlorophenylphosphine (2.99 mL, 22
mmol) was added in one portion. After stirring for 10 min at
-78.degree. C., the mixture was slowly warmed to room temperature,
and stirred for 1.5 h at room temperature. The mixture was then
cooled to -78.degree. C. again, and a solution of 1-naphthyllithium
(prepared from 1-bromonaphthalene (5.38 g, 26 mmol) and 1.7 M
t-BuLi solution in pentane (30.6 mL, 52 mmol) in Et.sub.2O (120 mL)
at -78.degree. C.] was added slowly via a cannula. The mixture was
warmed to room temperature overnight, and filtered through a pad of
Celite. The filtrate was concentrated, and the residue was purified
by chromatography (SiO.sub.2, hexane-EtOAc-Et.sub.3N=90:6:4) to
afford the title compound (8.75 g, 89%) as orange crystals. .sup.1H
NMR (CDCl.sub.3, 400.13 MHz): .delta. 1.33 (d, 3H, J=6.8 Hz); 1.91
(s, 6H); 3.59 (s, 5H); 4.00 (m, 1H); 4.17 (m, 1H); 4.26 (t, 1H,
J=2.2 Hz); 4.38 (m, 1H); 7.13.about.7.2 (m, 5H); 7.39 (t, 1H, J=6.7
Hz); 7.43.about.7.54 (m, 2H); 7.60.about.7.63 (m, 1H); 7.87 (dd,
2H, J=9.7 and 9.2 Hz), 9.33 (dd, H, J=7.6 and 7.0 Hz). .sup.31P NMR
(CDCl.sub.3, 162 MHz): .delta. -38.73.
EXAMPLE 3
(R.sub.C,S.sub.Fe,S.sub.P)-2-[(1-N,N-Dimethylamino)ethyl]-1-[(1-naphthyl)p-
henylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-3] and
(R.sub.C,S.sub.Fe,R.sub.P)-2-[(1-N,N-Dimethylamino)ethyl]-1-[(1-naphthyl)-
phenylphosphino]ferrocene [(R.sub.C,S.sub.Fe,R.sub.P)-4]
##STR00055##
[0072] To a solution of (R)--N,N-dimethyl-1-ferrocenylethylamine
[(R)-Ugi's amine, (R)-1] (1.29 g, 5 mmol) in Et.sub.2O (15 mL) was
added 1.7 M t-BuLi solution in pentane (3.2 mL, 5.5 mmol) over 10
min via a syringe at -78.degree. C. After addition was completed,
the mixture was warmed to room temperature, and stirred for 1.5 h
at room temperature. The resulting red solution was cooled to
-78.degree. C. again, and dichlorophenylphosphine (0.75 mL, 5.5
mmol) was added in one portion. After stirring for 10 min at
-78.degree. C., the mixture was slowly warmed to room temperature,
and stirred for 1.5 h at room temperature. Then to the mixture a
solution of 1-naphthyllithium [prepared from 1-bromonaphthalene
(1.35 g, 6.5 mmol) and 1.7 M t-BuLi solution in pentane (7.6 mL, 13
mmol) in Et.sub.2O (30 mL) at -78.degree. C.] was added via a
cannula at room temperature. The mixture was stirred overnight at
room temperature and filtered through a pad of Celite. The filtrate
was concentrated, and the residue was purified by chromatography
(SiO.sub.2, hexane-EtOAc-Et.sub.3N=85:10:5) to afford the title
compound (2.21 g, 90%) as a mixture of two isomers. The ratio of
(R.sub.C,S.sub.Fe,S.sub.P)-3 to (R.sub.C,S.sub.Fe,R.sub.P)-4 is
about 5:1. As (R.sub.C,S.sub.Fe,R.sub.P)-4 is insoluble in cold
hexane and (R.sub.C,S.sub.Fe, S.sub.P)-3 is very soluble in cold
hexane, the two isomers can be easily separated by crystallization
from hexane. (R.sub.C,S.sub.Fe,R.sub.P)-4: .sup.1H NMR (CDCl.sub.3,
400.13 MHz): .delta. 1.25 (d, 3H, J=6.8 Hz); 1.60 (s, 6H); 3.88
(br. s, 1H); 4.00 (s, 5H); 4.16 (m, 1H), 4.29 (t, 1H, J=2.2 Hz);
4.42 (br. s, 1H); 7.16.about.7.19 (m, 1H); 7.28.about.7.29 (m, 5H),
7.32.about.7.35 (m, 1H); 7.59.about.7.63 (m, 2H); 7.69 (d, J=8.2
Hz); 7.76 (d, J=7.6 Hz); 8.45 (m, 1H). .sup.31P NMR (CDCl.sub.3,
162 MHz): .delta. 31.36. The absolute configuration of
(R.sub.C,S.sub.Fe,R.sub.P)-4 was determined by single-crystal X-ray
diffraction analysis.
EXAMPLE 4
(R.sub.C,S.sub.Fe,R.sub.P)-2-[(1-N,N-Dimethylamino)ethyl]-1-[(1-naphthyl)p-
henylphosphino]ferrocene[(R.sub.C,S.sub.Fe,R.sub.P)-4]
##STR00056##
[0074] A solution of (R.sub.C,S.sub.Fe,S.sub.P)-3 (491 mg, 1.0
mmol) in hexane (5 mL) was refluxed overnight. After cooling to
room temperature, the precipitate was filtered and 5 washed with
cold hexane to give the pure (R.sub.C,S.sub.Fe,R.sub.P).sub.4.
EXAMPLE 5
(R.sub.C,S.sub.Fe,S.sub.P)-2-[(1-N,N-Dimethylamino)ethyl]-1-[(2-naphthyl)p-
henylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-5] and
(R.sub.C,S.sub.Fe,R.sub.P)-2-[(1-N,N-Dimethylamino)ethyl]-1-[(2-naphthyl)-
phenylphosphino]ferrocene [(R.sub.C,S.sub.Fe,R.sub.P)-6]
##STR00057##
[0076] To a solution of (R)--N,N-dimethyl-1-ferrocenylethylamine
[(R)-Ugi's amine, (R)-1] (2.57 g, 5 mmol) in Et.sub.2O (15 mL) was
added 1.7 M t-BuLi solution in pentane (6.4 mL, 11 mmol) over 10
min via a syringe at -78.degree. C. After addition was completed,
the mixture was warmed to room temperature, and stirred for 1.5 h
at room temperature. The resulting red solution was cooled to
-78.degree. C. again, and dichlorophenylphosphine (1.5 mL, 11 mmol)
was added in one portion. After stirring for 10 min at -78.degree.
C., the mixture was slowly warmed to room temperature, and stirred
for 1.5 h at room temperature. Then the mixture was cooled to
-78.degree. C. again, and a suspension of 2-naphthyllithium
[prepared from 2-bromonaphthalene (2.69 g, 13 mmol) and 1.7 M
t-BuLi solution in pentane (15.2 mL, 26 mmol) in Et.sub.2O (60 mL)
at -78.degree. C.] was added via a cannula at -78.degree. C. The
mixture was warmed to room temperature overnight and filtered
through a pad of Celite. The filtrate was concentrated, and the
residue was purified by chromatography (SiO.sub.2,
hexane-EtOAc-Et.sub.3N=85:10:5) to afford the title compound (4.42
g, 90%) as a mixture of two isomers. The ratio of
(R.sub.C,S.sub.Fe,S.sub.P)-5 to (R.sub.C,S.sub.Fe,R.sub.P)-6 is
about 5:1. Fractional crystallization from hexane gave
(R.sub.C,S.sub.Fe,S.sub.P)-5 (3.10 g, 63%) and
(R.sub.C,S.sub.Fe,R.sub.P)-6 (687 mg, 14%).
(R.sub.C,S.sub.Fe,S.sub.P)-5: .sup.1H NMR (CDCl.sub.3, 400.13 MHz):
.delta. 1.28 (d, 3H, J=6.2 Hz); 1.80 (s, 6H); 3.90 (br. s, 1H);
3.92 (s, 5H); 4.20 (m, 1H), 4.22 (t, 1H, J=2.2 Hz); 4.38 (br. s,
1H); 7.18.about.7.26 (m, 5H); 7.48 (m, 2H), 7.58 (ddd, 1H, J=8.4,
5.6 and 1.6 Hz); 7.79 (d, 1H, J=8.4 Hz); 7.83 (m, 2H); 8.18 (d, 1H,
J=9.5 Hz); .sup.31P NMR (CDCl.sub.3, 162 MHz): .delta. -20.88.
(R.sub.C, S.sub.Fe,R.sub.P).sub.6: .sup.1H NMR (CDCl.sub.3, 400.13
MHz): .delta. 1.27 (d, 3H, J=5.7 Hz); 1.76 (s, 6H); 3.90 (br. s,
1H); 3.96 (s, 5H); 4.18 (m, 1H), 4.29 (t, 1H, J=2.2 Hz); 4.41 (br.
s, 1H); 7.29 (ddd, 1H, J=8.3, 7.0 and 1.6 Hz); 7.34 (m, 3H); 7.39
(m, 2H); 7.59.about.7.67 (m, 5H), 7.74 (m, 1H); .sup.31P NMR
(CDCl.sub.3, 162 MHz): .delta. -20.57.
EXAMPLE 6
(R.sub.C,S.sub.Fe,S.sub.P)-2-[(1-N,N-Dimethylamino)ethyl]-1-[(2-naphthyl)p-
henylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-5]
##STR00058##
[0078] To a solution of (R)--N,N-dimethyl-1-ferrocenylethylamine
[(R)-Ugi's amine, (R)-1] (2.06 g, 8 mmol) in Et.sub.2O (15 mL) was
added 1.5 M t-BuLi solution in pentane (6.0 mL, 9 mmol) over 10 min
via a syringe at -78.degree. C. After addition was completed, the
mixture was warmed to room temperature, and stirred for 1.5 h at
room temperature. The resulting red solution was cooled to
-78.degree. C. again, and dichlorophenylphosphine (1.22 mL, 9 mmol)
was added in one portion. After stirring for 10 min at -78.degree.
C., the mixture was slowly warmed to room temperature, and stirred
for 1.5 h at room temperature. Then the mixture was cooled to
-78.degree. C. again, and a solution of 2-naphthylmagnesium bromide
[prepared from 2-bromonaphthalene (2.20 g, 10.6 mmol) and magnesium
(258 mg, 10.6 mmol) in Et.sub.2O (20 mL)] was added via a cannula
at -78.degree. C. The mixture was warmed to room temperature
overnight. The reaction was quenched with saturated NH.sub.4Cl
solution (20 mL). The organic layer was separated, and the aqueous
layer was extracted with Et.sub.2O (20 mL). The combined organic
layers were washed with brine (20 mL), dried (MgSO4), and
concentrated. The residue was purified by chromatography
(SiO.sub.2, hexane-EtOAc-Et.sub.3N=85:10:5) to afford the title
compound (3.42 g, 87%) as single diastereomer. .sup.1H NMR
(CDCl.sub.3, 400.13 MHz): .delta. 1.28 (d, 3H, J=6.2 Hz); 1.80 (s,
6H); 3.90 (br. s, 1H); 3.92 (s, 5H); 4.20 (m, 1H), 4.22 (t, 1H,
J=2.2 Hz); 4.38 (br. s, 1H); 7.18.about.7.26 (m, 5H); 7.48 (m, 2H),
7.58 (ddd, 1H, J=8.4, 5.6 and 1.6 Hz); 7.79 (d, 1H, J=8.4 Hz); 7.83
(m, 2H); 8.18 (d, 1H, J=9.5 Hz); .sup.31P NMR (CDCl.sub.3, 162
MHz): .delta. -20.88.
EXAMPLE 7
(R.sub.C,S.sub.Fe,S.sub.P)-2-[(1-N,N-Dimethylamino)ethyl]-1-[(2-biphenyl)p-
henylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-7]
##STR00059##
[0080] To a solution of (R)--N,N-dimethyl-1-ferrocenylethylamine
[(R)-Ugi's amine, (R)-1] (2.57 g, 10 mmol) in Et.sub.2O (20 mL) was
added 1.5 M t-BuLi solution in pentane (7.33 mL, 11 mmol) over 10
min via a syringe at -78.degree. C. After addition was completed,
the mixture was warmed to room temperature, and stirred for 1.5 h
at room temperature. The resulting red solution was cooled to
-78.degree. C. again, and dichlorophenylphosphine (1.50 mL, 11
mmol) was added in one portion. After stirring for 10 min at
-78.degree. C., the mixture was slowly warmed to room temperature,
and stirred for 1.5 h at room temperature. Then the mixture was
cooled to -78.degree. C. again, and a suspension of
2-biphenyllithium [prepared from 2-bromobiphenyl (2.24 mL, 13 mmol)
and 1.5 M t-BuLi solution in pentane (17.3 mL, 26 mmol) in
Et.sub.2O (30 mL) at -78.degree. C.] was added via a cannula at
-78.degree. C. The mixture was warmed to room temperature overnight
and filtered through a pad of Celite. The filtrate was
concentrated, and the residue was purified by chromatography
(SiO.sub.2, hexane-EtOAc-Et.sub.3N=85:10:5) to afford the title
compound (4.87 g, 94%) as single diastereomer. .sup.1H NMR
(CDCl.sub.3, 400.13 MHz): .delta. 1.25 (d, 3H, J=6.7 Hz); 1.85 (s,
6H); 3.69 (s, 5H); 3.76 (m, 1H), 4.17 (m, 1H), 4.29 (t, 1H, J=2.4
Hz); 4.32 (m, 1H); 7.10.about.7.19 (m, 5H); 7.31 (m, 1H),
7.37.about.7.48 (m, 5H), 7.64 (m, 1H); 7.69 (m, 1H); 7.71 (m, 1H).
.sup.31P NMR (CDCl.sub.3, 162 MHz): .delta. -32.96
EXAMPLE 8
(R.sub.C,S.sub.Fe,S.sub.P)-2-[(1-N,N-Dimethylamino)ethyl]-1-(methylphenylp-
hosphino)ferrocene[(R.sub.C,S.sub.Fe,R.sub.P)-8]
##STR00060##
[0082] To a solution of (R)--N,N-dimethyl-1-ferrocenylethylamine
[(R)-Ugi's amine, (R)-1] (2.57 g, 10 mmol) in Et.sub.2O (20 mL) was
added 1.5 M t-BuLi solution in pentane (7.33 mL, 11 mmol) over 10
min via a syringe at -78.degree. C. After addition was completed,
the mixture was warmed to room temperature, and stirred for 1.5 h
at room temperature. The resulting red solution was cooled to
-78.degree. C. again, and dichlorophenylphosphine (1.50 mL, 11
mmol) was added in one portion. After stirring for 10 min at
-78.degree. C., the mixture was slowly warmed to room temperature,
and stirred for 1.5 h at room temperature. Then the mixture was
cooled to -78.degree. C. again, and 3.0 M solution of MeMgBr in
Et.sub.2O (4.0 mL, 12 mmol) was added via a syringe at -78.degree.
C. The mixture was warmed to room temperature overnight. The
reaction was quenched with saturated NH.sub.4Cl solution (20 mL).
The organic layer was separated, and the aqueous layer was
extracted with Et.sub.2O (20 mL). The combined organic layers were
washed with brine (20 mL), dried (MgSO.sub.4), and concentrated.
The residue was purified by chromatography (SiO.sub.2,
hexane-EtOAc-Et.sub.3N=85:10:5) to afford the title compound (3.36
g, 89%) as red oil. .sup.1H NMR (CDCl.sub.3, 400.13 MHz): .delta.
1.24 (d, 3H, J=6.7 Hz); 1.56 (d, 3H, J=4.4 Hz); 1.72 (s, 6H); 4.07
(m, 1H), 4.13 (s, 5H); 4.30 (m, 1H), 4.34 (m, 2H); 7.14.about.7.20
(m, 3H); 7.30.about.7.37 (m, 2H). .sup.31P NMR (CDCl.sub.3, 162
MHz): .delta. -43.47
EXAMPLE 9
(R.sub.C,S.sub.Fe,S.sub.P)-2-[(1-N,N-Dimethylamino)ethyl]-1-(cyclohexylphe-
nylphosphino)ferrocene[(R.sub.C,S.sub.Fe,R.sub.P)-9]
##STR00061##
[0084] To a solution of (R)--N,N-dimethyl-1-ferrocenylethylamine
[(R)-Ugi's amine, (R)-1] (2.57 g, 10 mmol) in Et.sub.2O (20 mL) was
added 1.5 M t-BuLi solution in pentane (7.35 mL, 11 mmol) over 10
min via a syringe at -78.degree. C. After addition was completed,
the mixture was warmed to room temperature, and stirred for 1.5 h
at room temperature. The resulting red solution was cooled to
-78.degree. C. again, and dichlorophenylphosphine (1.50 mL, 11
mmol) was added in one portion. After stirring for 10 min at
-78.degree. C., the mixture was slowly warmed to room temperature,
and stirred for 1.5 h at room temperature. Then the mixture was
cooled to -78.degree. C. again, and 2.0 M solution of
cyclohexymagnesium chloride in Et.sub.2O (6.0 mL, 12 mmol) was
added via a syringe at -78.degree. C. The mixture was warmed to
room temperature overnight. The reaction was quenched with
saturated NH.sub.4Cl solution (20 mL). The organic layer was
separated, and the aqueous layer was extracted with Et.sub.2O (20
mL). The combined organic layers were washed with brine (20 mL),
dried (MgSO.sub.4), and concentrated. The residue was purified by
chromatography (SiO.sub.2, hexane-EtOAc-Et.sub.3N=90:5:5) to afford
the title compound (4.09 g, 92%) as red oil. .sup.1H NMR
(CDCl.sub.3, 400.13 MHz): .delta. 1.16 (d, 3H, J=6.7 Hz);
1.19.about.2.03 (m, 11H); 1.50 (s, 6H); 3.99 (m, 1H), 4.11 (s, 5H);
4.30 (m, 1H), 4.32 (t, 1H, J=2.5 Hz); 4.37 (m, 1H),
7.12.about.7.150 (m, 3H); 7.18.about.7.23 (m, 2H). .sup.31P NMR
(CDCl.sub.3, 162 MHz): .delta. -14.86
EXAMPLE 10
(R.sub.C,S.sub.Fe,S.sub.P)-2-[(1-N,N-Dimethylamino)ethyl]-1-[methyl(tert-b-
utyl)phenylphosphino)ferrocene[(R.sub.C,S.sub.Fe,R.sub.P)-10]
##STR00062##
[0086] To a solution of (R)--N,N-dimethyl-1-ferrocenylethylamine
[(R)-Ugi's amine, (R)-1] (1.29 g, 5 mmol) in Et.sub.2O (15 mL) was
added 1.5 M t-BuLi solution in pentane (3.7 mL, 5.5 mmol) over 10
min via a syringe at -78.degree. C. After addition was completed,
the mixture was warmed to room temperature, and stirred for 1.5 h
at room temperature. The resulting red solution was cooled to
-78.degree. C. again, and tert-butyldichlorophosphine (875 mg, 5.5
mmol) was added in one portion. After stirring for 10 min at
-78.degree. C., the mixture was slowly warmed to room temperature,
and stirred for 1.5 h at room temperature. Then to the mixture a
1.6 M solution of methyllithium in Et.sub.2O (3.75 mL, 6.0 mmol)
was added via a syringe at -78.degree. C. The mixture was warmed to
room temperature overnight and filtered through a pad of Celite.
The filtrate was concentrated, and the residue was purified by
chromatography (SiO.sub.2, hexane-EtOAc-Et.sub.3N=90:5:5) to afford
the title compound (1.54 g, 86%) as red oil. .sup.1H NMR
(CDCl.sub.3, 250.13 MHz): .delta. 1.09 (d, 9H, J=12.0 Hz), 1.27 (d,
3H, J=6.7 Hz); 1.45 (d, 3H, J=3.3 Hz); 2.08 (s, 6H); 3.92 (m, 1H),
4.10 (s, 5H), 4.28 (m, 3H). .sup.31P NMR (CDCl.sub.3, 101 MHz):
.delta. -6.47
EXAMPLE 11
(R.sub.C,S.sub.Fe,S.sub.P)-2-(1-Acetoxyethyl)-1-[(2-methoxyphenyl)phenylph-
osphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-11]
##STR00063##
[0088] A solution of (R.sub.C,S.sub.Fe,S.sub.P)-2 (1.18 g, 2.5
mmol) in acetic anhydride (10 mL) was stirred for 60 h at room
temperature. The excess acetic anhydride was removed under reduced
pressure (<1 Torr, <30.degree. C.) to give the title compound
(1.21 g, 100%) as yellow solid, which is pure enough for the use in
the next reaction. .sup.1H NMR (CDCl.sub.3, 400.13 MHz): .delta.
1.19 (s, 3H); 1.64 (d, 3H, J=6.5 Hz); 3.90 (s, 3H); 3.92 (m, 1H);
4.07 (s, 5H); 4.34 (t, 1H, J=2.6 Hz); 5.55 (m, 1H); 6.15 (m, 1H);
6.87 (td, 1H, J=7.4 and 0.9 Hz); 6.95 (q, 1H, J=4.8 Hz);
7.08.about.7.21 (m, 6H); 7.35 (m, 1H); .sup.31P NMR (CDCl.sub.3,
162 MHz): .delta. 39.30.
EXAMPLE 12
(R.sub.C,S.sub.Fe,S.sub.P)-2-(1-Acetoxyethyl)-1-[(1-naphthyl)phenylphosphi-
no]ferrocene [(R.sub.C, S.sub.Fe,S.sub.P)-12]
##STR00064##
[0090] A solution of (R.sub.C,S.sub.Fe,S.sub.P)-3 (1.47 g, 3.0
mmol) in acetic anhydride (20 mL) was stirred for 60 h at room
temperature. The excess acetic anhydride was removed under reduced
pressure (<1 Torr, <30.degree. C.) to give the title compound
(1.52 g, 100%) as yellow solid, which is pure enough for the use in
the next reaction. .sup.1H NMR (CDCl.sub.3, 400.13 MHz): .delta.
1.29 (s, 3H); 1.67 (d, 3H, J=6.5 Hz); 3.72 (s, 5H); 3.94 (m, 1H);
4.35 (t, 1H, J=2.6 Hz); 4.57 (m, 1H); 6.28 (m, 1H); 7.13.about.7.22
(m, 5H); 7.38.about.7.43 (m, 2H), 7.53 (ddd, 1H, J=8.0, 6.7 and 1.1
Hz), 7.64 (ddd, 1H, J=8.4, 6.8 and 1.4 Hz), 7.89 (t, 2H, J=7.0 Hz);
9.28 (t, 1H, J=7.0 Hz); .sup.31P NMR (CDCl.sub.3, 162 MHz): .delta.
-39.81.
EXAMPLE 13
(R.sub.C,S.sub.Fe,R.sub.P)-2-(1-Acetoxyethyl)-1-[(1-naphthyl)phenylphosphi-
no]ferrocene [(R.sub.C,S.sub.Fe,R.sub.P)-13]
##STR00065##
[0092] A solution of (R.sub.C,S.sub.Fe,R.sub.P)-4 (1.47 g, 3.0
mmol) in acetic anhydride (20 mL) was stirred for 60 h at room
temperature. The excess acetic anhydride was removed under reduced
pressure (<1 Torr, <30.degree. C.) to give the title compound
(1.52 g, 100%) as yellow solid, which is pure enough for the use in
the next reaction. .sup.1H NMR (CDCl.sub.3, 400.13 MHz): .delta.
0.83 (s, 3H); 1.62 (d, 3H, J=6.5 Hz); 3.83 (m, 1H); 4.10 (s, 5H);
4.40 (t, 1H, J=2.6 Hz); 5.61 (m, 1H); 6.21 (m, 1H); 7.11 (ddd, 1H,
J=7.0, 4.6 and 1.1 Hz), 7.28.about.7.41 (m, 6H); 7.55.about.7.43
(m, 2H), 7.75 (m, 2H), 8.29 (m, 1H); .sup.31P NMR (CDCl.sub.3, 162
MHz): .delta. -31.33.
EXAMPLE 14
(R.sub.C,S.sub.Fe,S.sub.P)-2-(1-Acetoxyethyl)-1-[(2-naphthyl)phenylphosphi-
no]ferrocene [(R.sub.C,S.sub.Fe,S.sub.P)-14]
##STR00066##
[0094] A solution of (R.sub.C,S.sub.Fe, S.sub.P)-5 (1.47 g, 3.0
mmol) in acetic anhydride (20 mL) was stirred for 60 h at room
temperature. The excess acetic anhydride was removed under reduced
pressure (<1 Torr, <30.degree. C.) to give the title compound
(1.52 g, 100%) as yellow solid, which is pure enough for the use in
the next reaction. .sup.1H NMR (CDCl.sub.3, 400.13 MHz): .delta.
1.21 (s, 3H); 1.65 (d, 3H, J=6.5 Hz); 3.83 (m, 1H); 4.03 (s, 5H);
4.33 (t, 1H, J=2.6 Hz); 4.57 (m, 1H); 6.24 (m, 1H); 7.19.about.7.27
(m, 5H); 7.46.about.7.51 (m, 3H), 7.81 (m, 3H), 8.11 (d, 1H, J=10.4
Hz); .sup.31P NMR (CDCl.sub.3, 162 MHz): .delta. -22.89.
EXAMPLE 15
(R.sub.C,S.sub.Fe,R.sub.P)-2-(1-Acetoxyethyl)-1-[(2-naphthyl)phenylphosphi-
no]ferrocene [(R.sub.C,S.sub.Fe,R.sub.P)-15]
##STR00067##
[0096] A solution of (R.sub.C,S.sub.Fe,R.sub.P)-6 (1.47 g, 3.0
mmol) in acetic anhydride (20 mL) was stirred for 60 h at room
temperature. The excess acetic anhydride was removed under reduced
pressure (<1 Torr, <30.degree. C.) to give the title compound
(1.52 g, 100%) as yellow solid, which is pure enough for the use in
the next reaction. .sup.1H NMR (CDCl.sub.3, 400.13 MHz): .delta.
0.92 (s, 3H); 1.64 (d, 3H, J=6.4 Hz); 3.87 (m, 1H); 4.07 (s, 5H);
4.40 (t, 1H, J=2.6 Hz); 5.61 (m, 1H); 6.23 (m, 1H); 7.27 (ddd, 1H,
J=8.2, 6.8 and 1.4 Hz), 7.32.about.7.38 (m, 3H): 7.39.about.7.44
(m, 2H), 7.53.about.7.57 (m, 2H), 7.60 (d, 1H, J=8.0 Hz), 7.69 (m,
2H), 7.74 (m, 1H); .sup.31P NMR (CDCl.sub.3, 162 MHz): .delta.
-22.58.
EXAMPLE 16
(R.sub.C,S.sub.Fe,S.sub.P)-2-(1-Acetoxyethyl)-1-[(2-biphenyl)phenylphosphi-
no]ferrocene [(R.sub.C,S.sub.Fe,S.sub.P)-16]
##STR00068##
[0098] A solution of (R.sub.C,S.sub.Fe,S.sub.P)-7 (1.47 g, 3.0
mmol) in acetic anhydride (20 mL) was stirred for 60 h at room
temperature. The excess acetic anhydride was removed under reduced
pressure (<1 Torr, <30.degree. C.) to give the title compound
(1.52 g, 100%) as yellow solid, which is pure enough for the use in
the next reaction. .sup.1H NMR (CDCl.sub.3, 400.13 MHz): .delta.
1.25 (s, 3H); 1.52 (d, 3H, J=6.5 Hz); 3.73 (s, 5H); 3.96 (m, 1H);
4.33 (t, 1H, J=2.6 Hz); 4.48 (m, 1H); 5.81 (m, 1H); 7.16.about.7.27
(m, 6H); 7.38.about.7.51 (m, 6H), 7.70.about.7.73 (m, 2H). .sup.31P
NMR (CDCl.sub.3, 162 MHz): .delta. -35.03.
EXAMPLE 17
(R.sub.C,S.sub.Fe,S.sub.P)-2-[(1-N-Methylamino)ethyl]-1-[(2-methoxyphenyl)-
phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-17]
##STR00069##
[0100] A solution of (R.sub.C,S.sub.Fe,S.sub.P)-11 (1.21 g, 2.5
mmol) and 40% methylamine aqueous solution (6.0 mL) in THF (20 mL)
and MeOH (5 mL) was stirred for 3 days at 40.degree. C., and
concentrated. The residue was dissolved in Et.sub.2O (20 mL),
washed with brine (10 mL), dried (Na.sub.2SO.sub.4), and evaporated
under reduced pressure. The crude product was purified by
chromatography (SiO.sub.2, hexane-EtOAc-Et.sub.3N=80:15:5) to give
the title compound (1.07 g, 94%) as orange crystals. .sup.1H NMR
(CDCl.sub.3, 250.13 MHz): .delta. 1.44 (d, 3H, J=6.5 Hz); 1.94 (s,
3H); 3.91 (m, 2H); 3.95 (s, 3H); 4.05 (s, 5H); 4.29 (t, 1H, J=2.5
Hz); 4.46 (m, 1H); 7.90 (dt, 1H, J=7.3 and 1.0 Hz), 6.97 (ddd, 1H,
J=8.3, 5.0 and 1.0 Hz), 7.15 (ddd, 1H, J=7.3, 5.5 and 1.8 Hz), 7.23
(m, 5H); 7.36 (ddd, 1H, J=8.3, 7.3 and 1.8 Hz), .sup.31P NMR
(CDCl.sub.3, 101 MHz): .delta. -41.43.
EXAMPLE 18
(R.sub.C,S.sub.Fe,S.sub.P)-2-[(1-N-Methylamino)ethyl]-1-[(1-naphthyl)pheny-
lphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-18]
##STR00070##
[0102] A solution of (R.sub.C,S.sub.Fe,S.sub.P)-12 (633 mg, 1.25
mmol) and 40% methylamine aqueous solution (3.0 mL) in THF (10 mL)
and MeOH (2.5 mL) was stirred for 3 days at 40.degree. C., and
concentrated. The residue was dissolved in Et.sub.2O (20 mL),
washed with brine (10 mL), dried (Na.sub.2SO.sub.4), and evaporated
under reduced pressure. The crude product was purified by
chromatography (SiO.sub.2, hexane-EtOAc-Et.sub.3N=85:10:5) to give
the title compound (549 mg, 92%) as orange crystals. .sup.1H NMR
(CDCl.sub.3, 400.13 MHz): .delta. 1.49 (d, 3H, J=6.6 Hz); 2.07 (s,
3H); 3.69 (s, 5H); 3.95 (m, 1H); 4.01 (m, 1H); 4.31 (t, 1H, J=2.5
Hz); 4.48 (m, 1H); 7.23 (m, 5H); 7.39.about.7.47 (m, 2H); 7.54 (m,
1H); 7.66 (m, 1H); 7.90 (t, 2H, J=7.9 Hz), 9.25 (dd, 1H, J=7.9 and
6.7 Hz). .sup.31P NMR (CDCl.sub.3, 162 MHz): .delta. -39.91.
EXAMPLE 19
(R.sub.C,S.sub.Fe,R.sub.P)-2-[(1-N-Methylamino)ethyl]-1-[(1-naphthyl)pheny-
lphosphino]ferrocene[(R.sub.C,S.sub.Fe,R.sub.P)-19]
##STR00071##
[0104] A solution of (R.sub.C,S.sub.Fe,R.sub.P)-7 (633 mg, 1.25
mmol) and 40% methylamine aqueous solution (3.0 mL) in THF (10 mL)
and MeOH (2.5 mL) was stirred for 3 days at 40.degree. C., and
concentrated. The residue was dissolved in Et.sub.2O (20 mL),
washed with brine (10 mL), dried (Na.sub.2SO.sub.4), and evaporated
under reduced pressure. The crude product was purified by
chromatography (SiO.sub.2, hexane EtOAc-Et.sub.3N=85:10:5) to give
the title compound (537 mg, 90%) as orange crystals. .sup.1H NMR
(CDCl.sub.3, 400.13 MHz): .delta. 1.45 (d, 3H, J=6.5 Hz); 1.83 (s,
3H); 3.82 (m, 1H); 3.97 (m, 1H); 4.07 (s, 5H); 3 4.35 (t, 1H, J=2.5
Hz); 4.53 (m, 1H); 7.20 (m, 1H); 7.30.about.7.36 (m, 5H); 7.40 (m,
1H); 7.56.about.7.61 (m, 2H); 7.78 (t, 2H, J=8.2 Hz), 8.38 (m, 1H).
.sup.31P NMR (CDCl.sub.3, 162 MHz): .delta. -32.25.
EXAMPLE 20
(R.sub.C,S.sub.Fe,S.sub.P)-2-[(1-N-Methylamino)ethyl-]-1-[(2-naphthyl)phen-
ylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-20]
##STR00072##
[0106] A solution of (R.sub.C,S.sub.Fe,S.sub.P)-14 (633 mg, 1.25
mmol) and 40% methylamine aqueous solution (3.0 mL) in THF (10 mL)
and MeOH (2.5 mL) was stirred for 3 days at 40.degree. C., and
concentrated. The residue was dissolved in Et.sub.2O (20 mL),
washed with brine (10 mL), dried (Na.sub.2SO.sub.4), and evaporated
under reduced pressure. The crude product was purified by
chromatography (SiO.sub.2, hexane-EtOAc-Et.sub.3N=85:10:5) to give
the title compound (513 mg, 86%) as orange crystals. .sup.1H NMR
(CDCl.sub.3, 400.13 MHz): .delta. 1.47 (d, 3H, J=6.7 Hz); 1.98 (s,
3H); 3.82 (m, 1H); 3.98 (m, 1H); 4.02 (s, 5H); 4.27 (t, 1H, J=2.5
Hz); 4.47 (m, 1H); 7.27.about.7.34 (m, 5H); 7.50 (m, 2H); 7.55 (m,
1H); 7.83 (m, 3H); 8.12 (d, 1H, J=10.0 Hz). .sup.31P NMR
(CDCl.sub.3, 162 MHz): .delta. -22.68.
EXAMPLE 21
(R.sub.C,S.sub.Fe,R.sub.P)-2-[(1-N-Methylamino)ethyl]-1-[(2-naphthyl)pheny-
lphosphino]ferrocene[(R.sub.C,S.sub.Fe,R.sub.P)-21]
##STR00073##
[0108] A solution of (R.sub.C,S.sub.Fe,R.sub.P)-15 (633 mg, 1.25
mmol) and 40% methylamine aqueous solution (3.0 mL) in THF (10 mL)
and MeOH (2.5 mL) was stirred for 3 days at room temperature, and
concentrated. The residue was dissolved in Et.sub.2O (20 mL),
washed with brine (10 mL), dried (Na.sub.2SO.sub.4), and evaporated
under reduced pressure. The crude product was purified by
chromatography (SiO.sub.2, hexane-EtOAc-Et.sub.3N 85:10:5) to give
the title compound (537 mg, 90%) as orange crystals.
EXAMPLE 22
(R.sub.C,S.sub.Fe,S.sub.P)-2-[(1-N-Methylamino)ethyl]-1-[(2-biphenyl)pheny-
lphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-22]
##STR00074##
[0110] A solution of (R.sub.C,S.sub.Fe,S.sub.P)-16 (1.063 g, 2
mmol) and 40% methylamine aqueous solution (5.0 mL) in THF (10 mL)
and MeOH (2.5 mL) was stirred for 2 days at 40.degree. C., and
concentrated. The residue was dissolved in Et.sub.2O (20 mL),
washed with brine (10 mL), dried (Na.sub.2SO.sub.4), and evaporated
under reduced pressure. The residue was recrystallized from hexane
to give the title compound (621 mg, 62%) as orange crystals.
.sup.1H NMR (CDCl.sub.3, 400.13 MHz): .delta. 1.34 (d, 3H, J=6.6
Hz); 1.93 (s, 3H); 3.60 (m, 1H); 3.74 (s, 5H); 4.08 (m, 1H); 4.30
(t, 1H, J=2.5 Hz); 4.39 (m, 1H); 7.19.about.7.24 (m, 5H); 7.31 (m,
1H); 7.38.about.7.50 (m, 5H), 7.59 (ddt, 1H, J=7.6, 3.5 and 1.0
Hz); 7.67 (m, 2H). .sup.31P NMR (CDCl.sub.3, 162 MHz): .delta.
-34.29.
EXAMPLE 23
(R.sub.C,S.sub.Fe,S.sub.P)-2-[1-[(N-Methyl-N-diphenylphosphino)amino]ethyl-
]-1-[(2-methoxyphenyl)phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-
-23]
##STR00075##
[0112] To a solution of (R.sub.C,S.sub.Fe,S.sub.P)-17 (457 mg, 1.0
mmol) and Et.sub.3N (0.28 mL, 2.0 mmol) in toluene (2.5 mL) was
added dropwise chlorodiphenylphosphine (188 uL, 1.05 mmol) at
0.degree. C. Then the mixture was warmed to room temperature, and
stirred overnight (16 h) at room temperature, and filtered through
a pad of neutral aluminium oxide and eluted with hexane-EtOAc (9:1)
to afford the title compound (570 mg, 89%) as orange foam. .sup.1H
NMR (CDCl.sub.3, 400.13 MHz): .delta. 1.55 (d, 3H, J=6.9 Hz); 2.17
(d, 3H, J=3.4 Hz); 3.87 (s, 8H, overlap); 4.24 (m, 1H); 4.38 (t,
1H, J=2.4 Hz); 4.53 (m, 1H); 4.88 (m, 1H); 6.88.about.6.96 (m, 6H);
7.03.about.7.14 (m, 6H); 7.20.about.7.37 (m, 7H). .sup.31P NMR
(CDCl.sub.3, 162 MHz): .delta. 56.93, -38.64.
EXAMPLE 24
(R.sub.C,S.sub.Fe,S.sub.P)-2-[1-[(N-Methyl-N-diphenylphosphino)amino]ethyl-
]-1-[(1-naphthyl)phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-24]
##STR00076##
[0114] To a solution of (R.sub.C,S.sub.Fe,S.sub.P)-18 (477 mg, 1.0
mmol) and Et.sub.3N (0.28 mL, 2.0 mmol) in toluene (2.5 mL) was
added dropwise chlorodiphenylphosphine (188 uL, 1.05 mmol) at
0.degree. C. Then the mixture was warmed to room temperature, and
stirred overnight (16 h) at room temperature, and filtered through
a pad of neutral aluminium oxide and eluted with hexane-EtOAc (9:1)
to afford the title compound (595 mg, 90%) as orange foam. .sup.1H
NMR (CDCl.sub.3, 400.13 MHz): .delta. 1.53 (d, 3H, J=6.8 Hz); 2.22
(d, 3H, J=3.3 Hz); 3.44 (s, 5H); 4.26 (m, 1H); 4.39 (t, 1H, J=2.4
Hz); 4.50 (m, 1H); 5.03 (m, 1H); 6.85.about.6.94 (m, 4H); 7.04 (tt,
1H, J=7.2 and 1.4 Hz); 7.09.about.7.19 (m, 4H); 7.27.about.7.31 (m,
4H); 7.37.about.7.43 (m, 3H); 7.48.about.7.56 (m, 2H); 7.68 (m,
1H); 7.89 (dd, 2H, J=8.1 and 4.8 Hz); 9.44 (t, 1H, J=7.6 Hz).
.sup.31P NMR (CDCl.sub.3, 162 MHz): .delta. 59.59, -41.03.
EXAMPLE 25
(R.sub.C,S.sub.Fe,R.sub.P)-2-[1-[(N-Methyl-N-diphenylphosphino)amino]ethyl-
]-1-[(1-naphthyl)phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,R.sub.P)-25]
##STR00077##
[0116] To a solution of (R.sub.C,S.sub.Fe,R.sub.P)-19 (239 mg, 0.5
mmol) and Et.sub.3N (0.14 mL, 1.0 mmol) in toluene (2.0 mL) was
added dropwise chlorodiphenylphosphine (89 uL, 0.50 mmol) at
0.degree. C. Then the mixture was warmed to room temperature, and
stirred overnight (16 h) at room temperature, and filtered through
a pad of neutral aluminium oxide and eluted with hexane-EtOAc (9:1)
to afford the title compound (304 mg, 92%) as orange foam. .sup.1H
NMR (CDCl.sub.3, 400.13 MHz): .delta. 1.51 (d, 3H, J=6.8 Hz); 2.08
(d, 3H, J=3.5 Hz); 3.90 (s, 5H); 4.15 (m, 1H); 4.44 (t, 1H, J=2.4
Hz); 4.58 (m, 1H); 5.02 (m, 1H); 6.44 (td, 2H, J=8.0 and 1.8 Hz);
6.62 (td, 2H, J=8.0 and 1.2 Hz); 6.80 (tt, 1H, J=7.4 and 1.2 Hz);
7.20 (m, 1H); 7.15.about.7.30 (m, H); 7.58.about.7.64 (m, H); 7.70
(dd, 1H, J=6.8 and 1.8 Hz); 7.79 (d, 1H, J=8.0 Hz); 8.20 (dd, 1H,
J=8.2 and 2.4 Hz). .sup.31P NMR (CDCl.sub.3, 162 MHz): .delta.
58.81, -31.16.
EXAMPLE 26
(R.sub.C,S.sub.Fe,S.sub.P)-2-[1-[(N-Methyl-N-diphenylphosphino)amino]ethyl-
]-1-[(2-biphenyl)phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-26]
##STR00078##
[0118] To a solution of (R.sub.C,S.sub.Fe,S.sub.P)-22 (XX mg, 1.0
mmol) and Et.sub.3N (0.28 mL, 2.0 mmol) in toluene (2.5 mL) was
added dropwise chlorodiphenylphosphine (188 uL, 1.05 mmol) at
0.degree. C. Then the mixture was warmed to room temperature, and
stirred overnight (16 h) at room temperature, and filtered through
a pad of neutral aluminium oxide and eluted with hexane-EtOAc (9:1)
to afford the title compound (XX mg, X %) as orange foam. .sup.1H
NMR (CDCl.sub.3, 250 MHz): .delta. 1.50 (d, 3H, J=6.6 Hz); 2.16 (d,
3H, J=3.0 Hz); 3.68 (s, 5H); 4.08 (m, 1H); 4.33 (m, 1H); 4.42 (m,
2H); 4.56 (m, 1H); 6.98.about.7.75 (m, 24H). .sup.31P NMR
(CDCl.sub.3, 101 MHz): .delta. 50.70, -35.51.
EXAMPLE 27
(R.sub.C,S.sub.Fe,S.sub.P,R.sub.a)-27
##STR00079##
[0120] To a solution of (R.sub.C,S.sub.Fe,S.sub.P)-17 (229 mg, 0.5
mmol) and Et.sub.3N (209 uL, 1.5 mmol) in toluene (4 mL) was added
(R)-4-chloro-3,5-dioxa-4-phosphacyclohepta[2,1-a:3,4-a']binaphthalene
(175 mg, 0.5 mmol) at 0.degree. C. Then the mixture was warmed to
room temperature, and stirred overnight (16 h) at room temperature,
and filtered through a pad of neutral aluminium oxide and eluted
with hexane-EtOAc (9:1) to afford the title compound (359 mg, 93%)
as orange foam. .sup.1H NMR (CDCl.sub.3, 250 MHz): .delta. 1.73 (d,
3H, J=3.5 Hz); 1.79 (d, 3H, J=7.0 Hz); 3.71 (s, 3H), 3.80 (m, 1H);
4.00 (s, 5H); 4.31 (t, 1H, J=2.3 Hz); 4.46 (m, 1H); 5.34 (m, 1H);
6.60 (ddd, 1H, J=7.5, 4.5 and 1.8 Hz), 6.72 (t, 1H, J=7.5 Hz), 6.82
(dd, 1H, J=8.8 and 0.8 Hz), 6.91 (ddd, 1H, J=8.8, 4.5 and 0.8 Hz),
7.15.about.7.38 (m, 11H), 7.58 (m, 2H), 7.77.about.7.87 (m, 4H).
.sup.31P NMR (CDCl.sub.3, 101 MHz): .delta. 148.51 (d, J=53.4 Hz);
-35.37 (d, J=53.4 Hz).
EXAMPLE 28
(R.sub.C,S.sub.Fe,S.sub.P,R.sub.a)-28
##STR00080##
[0122] To a solution of (R.sub.C,S.sub.Fe,S.sub.P)-18(239 mg, 0.5
mmol) and Et.sub.3N (209 uL, 1.5 mmol) in toluene (4 mL) was added
(R)-4-chloro-3,5-dioxa-4-phosphacyclohepta[2,1-a:3,4-a']binaphthalene
(175 mg, 0.5 mmol) at 0.degree. C. Then the mixture was warmed to
room temperature, and stirred overnight (16 h) at room temperature,
and filtered through a pad of neutral aluminium oxide and eluted
with hexane-EtOAc (9:1) to afford the title compound (376 mg, 95%)
as orange foam. .sup.1H NMR (CDCl.sub.3, 250 MHz): .delta. 0.87 (d,
3H, J=7.0 Hz); 1.82 (d, 3H, J=3.5 Hz); 3.62 (s, 5H); 4.06 (m, 1H);
4.33 (t, 1H, J=2.3 Hz); 4.46 (m, 1H); 5.43 (m, 1H); 6.69 (dd, 1H,
J=8.8 and 0.8 Hz), 7.07.about.7.93 (m, 22H), 9.39 (m, 1H). .sup.31P
NMR (CDCl.sub.3, 101 MHz): .delta. 148.37 (d, J=61.8 Hz); -41.59
(d, J=61.8 Hz).
EXAMPLE 29
(R.sub.C,S.sub.Fe,S.sub.P,S.sub.a)-29
##STR00081##
[0124] To a solution of (R.sub.C,S.sub.Fe,S.sub.P)-18(239 mg, 0.5
mmol) and Et.sub.3N (209 uL, 1.5 mmol) in toluene (4 mL) was added
(S)-4-chloro-3,5-dioxa-4-phosphacyclohepta[2,1-a:3,4-a']binaphthalene
(175 mg, 0.5 mmol) at 0.degree. C. Then the mixture was warmed to
room temperature, and stirred overnight (16 h) at room temperature,
and filtered through a pad of neutral aluminium oxide and eluted
with hexane-EtOAc (9:1) to afford the title compound (373 mg, 95%)
as orange foam. .sup.1H NMR (CDCl.sub.3, 250 MHz): .delta. 1.71 (d,
3H, J=7.0 Hz); 1.99 (d, 3H, J=3.3 Hz); 3.51 (s, 5H); 4.27 (m, 1H);
4.42 (t, 1H, J=2.3 Hz); 4.51 (m, 1H); 5.28 (m, 1H); 5.98 (d, 1H,
J=8.5 Hz), 7.10.about.7.95 (m, 22H), 9.42 (m, 1H). .sup.31P NMR
(CDCl.sub.3, 101 MHz): .delta. 150.23 (d, J=34.3 Hz); -44.84 (d,
J=34.3 Hz).
EXAMPLE 30
(R.sub.C,S.sub.Fe,R.sub.P,R.sub.a)-30
##STR00082##
[0126] To a solution of (R.sub.C,S.sub.Fe,R.sub.P)-19(239 mg, 0.5
mmol) and Et.sub.3N (209 uL, 1.5 mmol) in toluene (4 mL) was added
(R)-4-chloro-3,5-dioxa-4-phosphacyclohepta[2,1-a:3,4-a']binaphthalene
(175 mg, 0.5 mmol) at 0.degree. C. Then the mixture was warmed to
room temperature, and stirred overnight (16 h) at room temperature,
and filtered through a pad of neutral aluminium oxide and eluted
with hexane-EtOAc (9:1) to afford the title compound (371 mg, 95%)
as orange foam. .sup.1H NMR (CDCl.sub.3, 250 MHz): .delta. 1.64 (d,
3H, J=3.5 Hz); 1.79 (d, 3H, J=7.0 Hz); 4.88 (m, 1H); 4.07 (s, 5H);
4.38 (t, 1H, J=2.3 Hz); 4.52 (m, 1H); 4.91 (dd, 1H, J=8.5 and 0.8
Hz), 5.37 (m, 1H); 6.91 (m, 1H); 7.10.about.7.90 (m, 21H), 8.44 (m,
1H). .sup.31P NMR (CDCl.sub.3, 101 MHz): .delta. 148.18 (d, J=54.5
Hz); -32.43 (d, J=54.5 Hz).
EXAMPLE 31
(R.sub.C,S.sub.Fe, R.sub.P,S.sub.a)-31
##STR00083##
[0128] To a solution of (R.sub.C,S.sub.Fe,R.sub.P)-19(239 mg, 0.5
mmol) and Et.sub.3N (209 uL, 1.5 mmol) in toluene (4 mL) was added
(S)-4-chloro-3,5-dioxa-4-phosphacyclohepta[2,1-a:3,4-a']binaphthalene
(175 mg, 0.5 mmol) at 0.degree. C. Then the mixture was warmed to
room temperature, and stirred overnight (16 h) at room temperature,
and filtered through a pad of neutral aluminium oxide and eluted
with hexane-EtOAc (9:1) to afford the title compound (377 mg, 95%)
as orange foam. .sup.1H NMR (CDCl.sub.3, 250 MHz): .delta. 1.69 (d,
3H, J=6.8 Hz); 1.86 (d, 3H, J=3.5 Hz); 3.97 (s, 5H); 4.07 (m, 1H);
4.43 (t, 1H, J=2.3 Hz); 4.58 (m, 1H); 5.15 (m, 1H); 5.88 (dd, 1H,
J=8.5 and 0.8 Hz), 6.91 (m, 1H); 7.10.about.7.92 (m, 22H), 8.31 (m,
1H). .sup.31P NMR (CDCl.sub.3, 101 MHz): .delta. 150.64 (d, J=21.8
Hz); -33.31 (d, J=21.8 Hz).
EXAMPLE 32
(R.sub.C,S.sub.Fe,S.sub.P,R.sub.a)-32
##STR00084##
[0130] To a solution of (R.sub.C,S.sub.Fe,S.sub.P)-22(252 mg, 0.5
mmol) and Et.sub.3N (209 uL, 1.5 mmol) in toluene (4 mL) was added
(R)-4-chloro-3,5-dioxa-4-phosphacyclohepta[2,1-a:3,4-a']binaphthalene
(175 mg, 0.5 mmol) at 0.degree. C. Then the mixture was warmed to
room temperature, and stirred overnight (16 h) at room temperature,
and filtered through a pad of neutral aluminium oxide and eluted
with hexane-EtOAc (9:1) to afford the title compound (392 mg, 96%)
as orange foam. .sup.1H NMR (CDCl.sub.3, 250 MHz): .delta. 1.63 (d,
3H, J=7.0 Hz); 1.76 (d, 3H, J=3.5 Hz); 3.69 (s, 5H); 4.09 (m, 1H);
4.30 (t, 1H, J=2.3 Hz); 4.34 (m, 1H); 4.89 (m, 1H); 6.71 (dd, 1H,
J=8.5 and 0.8 Hz), 7.07.about.7.84 (m, 25H). .sup.31P NMR
(CDCl.sub.3, 101 MHz): .delta. 149.07 (d, J=60.5 Hz); -36.59 (d,
J=60.5 Hz).
EXAMPLE 33
(R.sub.C,S.sub.Fe,S.sub.P)-2-(1-Dicyclohexylphosphino)ethyl]-1-[(2-methoxy-
phenyl)phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-33]
##STR00085##
[0132] A solution of (R.sub.C,S.sub.Fe,S.sub.P)11 (486 mg, 1.0
mmol) and dicyclohexylphosphine (243 uL, 1.2 mmol) in acetic acid
(3 mL) was stirred overnight at room temperature, and poured into
10% K.sub.2CO.sub.3 aqueous solution (60 mL) with stirring,
extracted with Et.sub.2O (2.times.25 mL). The combined ether layers
were dried (MgSO.sub.4) and concentrated. The residue was purified
by chromatography (SiO.sub.2, hexane-EtOAc=9:1) to afford the title
compound (601 mg, 96%) as orange crystals. .sup.1H NMR (CDCl.sub.3,
250.13 MHz): .delta. 1.08.about.1.68 (m, 25H), 3.12 (m, 1H), 3.91
(s, 5H), 4.07 (m, 1H), 4.29 (t, 1H, J=2.3 Hz); 4.38 (m, 1H),
6.87.about.6.98 (m, 2H), 7.15.about.7.25 (m, 6H), 7.35 (t, 1H,
J=7.3 Hz); .sup.31P NMR (CDC.sub.3, 101.25 MHz): .delta. 15.58 (d,
J=23.2 Hz); -42.23 (d, J=23.2 Hz).
EXAMPLE 34
(R.sub.C,S.sub.Fe,S.sub.P)-2-(1-Dicyclohexylphosphino)ethyl]-1-[(1-naphthy-
l)phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-34]
##STR00086##
[0134] A solution of (R.sub.C,S.sub.Fe,S.sub.P)-12 (506 mg, 1.0
mmol) and dicyclohexylphosphine (243 uL, 1.2 mmol) in acetic acid
(3 mL) was stirred overnight at room temperature, and poured into
10% K.sub.2CO.sub.3 aqueous solution (60 mL) with stirring,
extracted with Et.sub.2O (2.times.25 mL). The combined ether layers
were dried (MgSO.sub.4) and concentrated. The residue was purified
by chromatography (SiO.sub.2, hexane-EtOAc=9:1) to afford the title
compound (613 mg, 95%) as orange crystals. .sup.1H NMR (CDCl.sub.3,
400.13 MHz): .delta. 1.14.about.1.57 (m, 25H); 3.22 (m, 1H); 3.40
(s, 5H); 4.08 (m, 1H); 4.23 (t, 1H, J=2.4 Hz); 4.31 (m, 1H);
7.16.about.7.22 (m, 5H); 7.36 (dd, 1H, J=8.0 and 7.2 Hz);
7.45.about.7.49 (m, 2H); 7.60 (ddd, 1H, J=8.5, 6.8 and 1.4 Hz);
7.82 (t, 2H, J=8.1 Hz); 9.28 (dd, 1H, J=7.6 and 6.8 Hz). .sup.31P
NMR (CDCl.sub.3, 162 MHz): .delta. 17.46 (d, J=27.7 Hz); 42.43 (d,
J=27.7 Hz).
EXAMPLE 35
(R.sub.C,S.sub.Fe,R.sub.P)-2-(1-Dicyclohexylphosphino)ethyl]-1-[(1-naphthy-
l)phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,R.sub.P)-35]
##STR00087##
[0136] A solution of (R.sub.C,S.sub.Fe,S.sub.P)-13 (506 mg, 1.0
mmol) and dicyclohexylphosphine (243 uL, 1.2 mmol) in acetic acid
(3 mL) was stirred overnight at room temperature, and poured into
10% K.sub.2CO.sub.3 aqueous solution (60 mL) with stirring,
extracted with Et.sub.2O (2.times.25 mL). The combined ether layers
were dried (MgSO.sub.4) and concentrated. The residue was purified
by chromatography (SiO.sub.2, hexane-EtOAc=9:1) to afford the title
compound (618 mg, 95%) as orange crystals. .sup.1H NMR (CDCl.sub.3,
250.13 MHz): .delta. 0.84.about.1.85 (m, 25H), 3.16 (m, 1H), 3.96
(s, 5H), 4.00 (m, 1H), 4.35 (t, 1H, J=2.3 Hz); 4.41 (m, 1H),
7.29.about.7.40 (m, 7H), 7.62.about.7.79 (m, 4H), 8.33 (m, 1H);
.sup.31P NMR (CDCl.sub.3, 101.25 MHz): .delta. 14.93 (d, J=22.8
Hz); -34.80 (d, J=22.8 Hz).
EXAMPLE 36
(R.sub.C,S.sub.Fe,S.sub.P)-2-(1-Dicyclohexylphosphino)ethyl]-1-[(2-naphthy-
l)phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-36]
##STR00088##
[0138] A solution of (R.sub.C,S.sub.Fe,S.sub.P)-14 (506 mg, 1.0
mmol) and dicyclohexylphosphine (243 uL, 1.2 mmol) in acetic acid
(3 mL) was stirred overnight at room temperature, and poured into
10% K.sub.2CO.sub.3 aqueous solution (60 mL) with stirring,
extracted with Et.sub.2O (2.times.25 mL). The combined ether layers
were dried (MgSO.sub.4) and concentrated. The residue was purified
by chromatography (SiO.sub.2, hexane-EtOAc=9:1) to afford the title
compound (599 mg, 93%) as orange crystals. .sup.1H NMR (CDCl.sub.3,
250.13 MHz): .delta. 1.15.about.1.71 (m, 25H), 3.26 (m, 1H), 3.79
(s, 5H), 4.10 (m, 1H), 4.29 (t, 1H, J=2.3 Hz); 4.37 (m, 1H),
7.17.about.7.24 (m, 5H), 7.34 (m, 1H), 7.50 (d, 1H, J=9.5 Hz); 7.50
(dd, 1H, J=3.0 and 1.5 Hz); 7.57 (ddd, 1H, J=8.3, 5.0 and 1.5 Hz);
7.81 (d, 1H, J=8.5 Hz); 7.87 (m, 1H), 8.31 (d, 1H, J=9.5 Hz);
.sup.31P NMR (CDCl.sub.3, 101.25 MHz): .delta. 15.67 (d, J=30.9
Hz); -34.20 (d, J=30.9 Hz).
EXAMPLE 37
(R.sub.C,S.sub.Fe,R.sub.P)-2-(1-Dicyclohexylphosphino)ethyl]-1-[(2-naphthy-
l)phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,R.sub.P)-37]
##STR00089##
[0140] A solution of (R.sub.C,S.sub.Fe,S.sub.P)-15 (506 mg, 1.0
mmol) and dicyclohexylphosphine (243 uL, 1.2 mmol) in acetic acid
(3 mL) was stirred overnight at room temperature, and poured into
10% K.sub.2CO.sub.3 aqueous solution (60 mL) with stirring,
extracted with Et.sub.2O (2.times.25 mL). The combined ether layers
were dried (MgSO.sub.4) and concentrated. The residue was purified
by chromatography (SiO.sub.2, hexane-EtOAc=9:1) to afford the title
compound (608 mg, 94%) as orange crystals. .sup.1H NMR (CDCl.sub.3,
250.13 MHz): .delta. 1.07.about.1.68 (m, 25H), 3.26 (m, 1H), 3.85
(s, 5H), 4.07 (m, 1H), 4.34 (t, 1H, J=2.3 Hz); 4.40 (m, 1H),
7.30.about.7.77 (m, 12H); .sup.31P NMR (CDCl.sub.3, 101.25 MHz):
.delta. 15.56 (d, J=33.1 Hz); -25.12 (d, J=33.1 Hz).
EXAMPLE 38
(R.sub.C,S.sub.Fe,S.sub.P)-2-(1-Dicyclohexylphosphino)ethyl]-1-[(2-bipheny-
l)phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-38]
##STR00090##
[0142] A solution of (R.sub.C,S.sub.Fe,S.sub.P)-16 (531 mg, 1.0
mmol) and dicyclohexylphosphine (243 uL, 1.2 mmol) in acetic acid
(3 mL) was stirred overnight at room temperature, and poured into
10% K.sub.2CO.sub.3 aqueous solution (60 mL) with stirring,
extracted with Et.sub.2O (2.times.25 mL). The combined ether layers
were dried (MgSO.sub.4) and concentrated. The residue was purified
by chromatography (SiO.sub.2, hexane-EtOAc=9:1) to afford the title
compound (650 mg, 97%) as orange crystals. .sup.1H NMR (CDCl.sub.3,
250.13 MHz): .delta. 1.02.about.1.72 (m, 25H), 2.93 (m, 1H), 3.66
(s, 5H), 3.76 (m, 1H), 4.29 (t, 1H, J=2.3 Hz); 4.32 (m, 1H),
7.14.about.7.69 (m, 14H); .sup.31P NMR (CDCl.sub.3, 101.25 MHz):
.delta. 18.44 (d, J=36.7 Hz); -37.67 (d, J=36.7 Hz).
EXAMPLE 39
(R.sub.C,S.sub.Fe,S.sub.P)-2,2'-Bis[(1-N,N-dimethylamino)ethyl]-1,1'-bis[(-
2-methoxyphenyl)phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-40]
##STR00091##
[0144] To a solution of
(R,R)-1,1'-bis(1-N,N-dimethylaminoethyl)ferrocene[(R,R)-20] (986
mg, 3.0 mmol) in Et.sub.2O (30 mL) was added 1.5 M t-BuLi solution
in pentane (6.0 mL, 9 mmol) over 10 min via a syringe at
-78.degree. C. After addition was completed, the mixture was warmed
to room temperature, and stirred for 1.5 h at room temperature. The
resulting red solution was cooled to -78.degree. C. again, and
dichlorophenylphosphine (1.22 mL, 9.0 mmol) was added in one
portion. After stirring for 10 min at -78.degree. C., the mixture
was slowly warmed to room temperature, and stirred for 1.5 h at
room temperature. The mixture was then cooled to -78.degree. C.
again, and a solution of (2-methoxy)phenyllithium [prepared from
2-bromoanisole (1.87 g, 10 mmol) and 1.5 M t-BuLi solution in
pentane (13.3 mL, 20 mmol) in Et.sub.2O (50 mL) at -78.degree. C.]
was added slowly via a cannula. The mixture was warmed to room
temperature overnight, and filtered through a pad of Celite. The
filtrate was concentrated. The residue was purified by
chromatography (SiO.sub.2, hexane-EtOAc-Et.sub.3N=80:15:5) to
afford the title compound (1.10 g, 48%) as yellow foam. .sup.1H NMR
(CDCl.sub.3, 400.13 MHz): .delta. 1.28 (d, 6H, J=6.7 Hz); 1.71 (s,
12H); 3.16 (m, 2H); 3.84 (s, 6H); 4.05 (m, 2H); 4.16 (m, 2H); 4.53
(t, 2H, J=2.3 Hz); 6.62 (t, 2H, J=7.4 Hz); 6.73 (dd, 2H, J=8.1 and
4.6 Hz); 6.85 (ddd, 2H, J=7.4, 5.3 and 1.8 Hz); 7.03.about.7.11 (m,
10H); 7.17 (td, 2H, J=8.5 and 1.6 Hz); .sup.31P NMR (CDCl.sub.3,
162 MHz): .delta. -39.53 (s).
EXAMPLE 40
(R.sub.C,S.sub.Fe,S.sub.P)-2,2'-Bis[(1-N,N-dimethylamino)ethyl]-1,1'-bis[(-
1-naphthyl)phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-41]
##STR00092##
[0146] To a solution of
(R,R)-1,1'-bis(1-N,N-dimethylaminoethyl)ferrocene[(R,R)20] (986 mg,
3.0 mmol) in Et.sub.2O (30 mL) was added 1.5 M t-BuLi solution in
pentane (6.0 mL, 9 mmol) over 10 min via a syringe at -78.degree.
C. After addition was completed, the mixture was warmed to room
temperature, and stirred for 1.5 h at room temperature. The
resulting red solution was cooled to -78.degree. C. again, and
dichlorophenylphosphine (1.22 mL, 9.0 mmol) was added in one
portion. After stirring for 10 min at -78.degree. C., the mixture
was slowly warmed to room temperature, and stirred for 1.5 h at
room temperature. The mixture was then cooled to -78.degree. C.
again, and a solution of 1-naphthyllithium [prepared from
1-bromonaphthalene (2.07 g, 10 mmol) and 1.5 M t-BuLi solution in
pentane (13.3 mL, 20 mmol) in Et.sub.2O (50 mL) at -78.degree. C.]
was added slowly via a cannula. The mixture was warmed to room
temperature overnight, and filtered through a pad of Celite. The
filtrate was concentrated. The residue was purified by
chromatography (SiO.sub.2, hexane-EtOAc-Et.sub.3N=80:15:5) to
afford the title compound (827 mg, 35%) as yellow crystals. .sup.1H
NMR (CDCl.sub.3, 400.13 MHz): .delta. 1.28 (d, 6H, J=6.8 Hz); 1.74
(s, 12H); 2.49 (m, 2H); 4.01 (t, 2H, J=2.3 Hz); 4.06 (m, 2H); 4.08
(m, 2H); 6.87.about.6.93 (m, 4H); 6.99.about.7.09 (m, 10H); 7.50
(td, 2H, J=8.1 and 1.1 Hz); 7.53 (td, 2H, J=6.8 and 1.3 Hz); 7.70
(d, 2H, J=8.1 Hz); 7.83 (d, 2H, J=8.1 Hz); 9.16 (t, 2H, J=7.1 Hz);
.sup.31P NMR (CDCl.sub.3, 162 MHz): .delta. -39.47 (s).
EXAMPLE 41
(R.sub.C,S.sub.Fe,S.sub.P)-2,2'-Bis[(a-N,N-dimethylamino)phenylmethyl]-1,1-
'-bis[(1-naphthyl)phenylphosphino]ferrocene[(R.sub.C,S.sub.Fe,S.sub.P)-43]
##STR00093##
[0148] To a solution of
(R,R)-1,1'-bis[(.alpha.-N,N-dimethylamino)phenylmethyl]ferrocene
[(R,R)-23] (903 mg, 2.0 mmol) in Et.sub.2O (20 mL) was added 1.5 M
t-BuLi solution in pentane (4.0 mL, 6 mmol) over 10 min via a
syringe at -78.degree. C. After addition was completed, the mixture
was warmed to room temperature, and stirred for 1.5 h at room
temperature. The resulting red solution was cooled to -78.degree.
C. again, and dichlorophenylphosphine (814 uL, 6.0 mmol) was added
in one portion. After stirring for 10 min at -78.degree. C., the
mixture was slowly warmed to room temperature, and stirred for 1.5
h at room temperature. The mixture was then cooled to -78.degree.
C. again, and a solution of 1-naphthyllithium [prepared from
1-bromonaphthalene (1.45 g, 7 mmol) and 1.5 M t-BuLi solution in
pentane (9.3 mL, 14 mmol) in Et.sub.2O (40 mL) at -78.degree. C.]
was added slowly via a cannula. The mixture was warmed to room
temperature overnight, and filtered through a pad of Celite. The
filtrate was concentrated. The residue was purified by
chromatography (SiO.sub.2, hexane-EtOAc=3:1) to afford the title
compound (369 mg, 20%) as orange crystals. .sup.1H NMR (CDCl.sub.3,
250.13 MHz): .delta. 1.54 (s, 12H); 2.46 (m, 2H); 3.01 (m, 2H);
3.96 (t, 2H, J=2.5 Hz); 4.42 (d, 2H, J=5.3 Hz); 6.69 (ddd, 2H,
J=7.3, 4.3 and 1.0 Hz); 6.96.about.7.34 (m, 22H); 7.55 (d, 2H,
J=8.3 Hz); 7.66 (d, 4H, J=8.3 Hz); 7.81 (d, 2H, J=7.8 Hz); 9.20 (t,
2H, J=7.8 Hz); .sup.31P NMR (CDCl.sub.3, 162 MHz): .delta. -41.73
(s).
EXAMPLE 42
(2'S,4'S,S.sub.Fe,R.sub.P)-2-[4'-(methoxymethyl-1,3-dioxan-2'-yl]-1-[(2-me-
thoxyphenyl)phenylphosphino]ferrocene[(2'S,4'S,S.sub.Fe,R.sub.P)-46]
##STR00094##
[0150] To a solution of
(2S,4S)-4-(methoxymethyl)-2-ferrocenyl-1,3-dioxane [(2S,4S)-45]
(1.58 g, 5 mmol) in Et.sub.2O (20 mL) was added 1.7 M t-BuLi
solution in pentane (3.23 mL, 5.5 mmol) at -40.degree. C. After
stirring for 10 min, the cooling bath was removed and the mixture
was warmed to room temperature, and stirred for 1.5 h at room
temperature. The resulting orange suspension was cooled to
-78.degree. C., and dichlorophenylphosphine (750 uL, 5.5 mmol) was
added in one portion. After stirring for 10 min, the cooling bath
was removed and the mixture was warmed to room temperature, and
stirred for 1.5 h at room temperature. The mixture was cooled to
-78.degree. C. again, a solution of 2-methoxyphenyllithium
[prepared from 2-bromoanisole (1.22 mL, 6.5 mmol) and 1.7 M t-BuLi
solution in pentane (7.6 mL, 13 mmol) in Et.sub.2O (40 mL) at
-78.degree. C.] was added slowly via a cannula. The mixture was
warmed to room temperature overnight, and filtered through a pad of
Celite. The filtrate was concentrated. The residue was purified by
chromatography (SiO.sub.2, hexane-EtOAc=6:1) to afford the title
compound (2.41 g, 91%) as a mixture of two diastereomers (in about
3.3:1 ratio). Recrystallising from hexane, the major product [(2'S,
4'S,S.sub.Fe,R.sub.P)-46] (1.41 g, 53%) was obtained. The absolute
configuration of (2'S, 4'S,S.sub.Fe,R.sub.P)-46 was determined by
single-crystal X-ray diffraction analysis. .sup.1H NMR (CDCl.sub.3,
400.13 MHz): .delta. 1.42 (dm, 1H, J=13.3 Hz); 1.74 (m, 1H); 2.89
(d, 2H, J=5.1 Hz); 3.03 (s, 3H); 3.59 (m, 1H); 3.60 (s, 3H); 3.74
(m, 1H); 3.91 (td, 1H, J=12.2 and 2.5 Hz); 4.08 (s, 5H);
4.24.about.4.27 (m, 2H); 4.70 (m, 1H); 5.71 (d, 1H, J=2.5 Hz); 6.74
(dd, 1H, J=7.9 and 4.6 Hz); 6.80.about.6.86 (m, 2H); 7.22 (m, 1H);
7.31.about.7.35 (m, 3H); 7.51.about.7.56 (m, 2H). .sup.31P NMR
(CDCl.sub.3, 162 MHz): .delta. -31.46 (s).
EXAMPLE 43
(2'S,4'S,S.sub.Fe,R.sub.P)-2-[4'-(methoxymethyl-1,3-dioxan-2'-yl]-1-[(1-na-
phthyl)phenylphosphino]ferrocene[(2'S,
4'S,S.sub.Fe,R.sub.P)-47]
##STR00095##
[0152] To a solution of
(2S,4S)-4-(methoxymethyl)-2-ferrocenyl-1,3-dioxane [(2S,4S)-45]
(3.16 g, 10 mmol) in Et.sub.2O (40 mL) was added 1.5 M t-BuLi
solution in pentane (7.4 mL, 11 mmol) at -40.degree. C. After
stirring for 10 min, the cooling bath was removed and the mixture
was warmed to room temperature, and stirred for 1.5 h at room
temperature. The resulting orange suspension was cooled to
-78.degree. C., and dichlorophenylphosphine (1.49 mL, 11 mmol) was
added in one portion. After stirring for 10 min, the cooling bath
was removed and the mixture was warmed to room temperature, and
stirred for 1.5 h at room temperature. The mixture was cooled to
-78.degree. C. again, a solution of 1-naphthyllithium [prepared
from 1-bromonaphthalene (1.67 mL, 12 mmol) and 1.5 M t-BuLi
solution in pentane (16 mL, 24 mmol) In Et.sub.2O (60 mL) at
-78.degree. C.] was added slowly via a cannula. The mixture was
warmed to room temperature overnight, and filtered through a pad of
Celite. The filtrate was concentrated. The residue was purified by
chromatography (SiO.sub.2, hexane-EtOAc=6:1) to afford the title
compound (4.95 g, 90%) as a mixture of two diastereomers (in about
3.4:1 ratio), which was recrystallised from hexane to give the pure
major product [(2'S, 4'S,S.sub.Fe, R.sub.P)-47] (2.53 g, 51%) as
yellow needles. The absolute configuration of (2'S,
4'S,S.sub.Fe,R.sub.P)-47 was determined by single-crystal X-ray
diffraction analysis. .sup.1H NMR (CDCl.sub.3, 400.13 MHz): .delta.
1.33 (dm, 1H, J=13.3 Hz); 1.63 (m, 1H); 2.56 (dd, 1H, J=10.3 and
4.8 Hz); 2.67 (dd, 1H, J=10.3 and 5.6 Hz); 2.76 (s, 3H); 3.58 (m,
1H); 3.67 (m, 1H); 3.86 (td, 1H, J=12.2 and 2.5 Hz); 4.15 (s, 5H);
3.74 (m, 1H); 4.21 (ddd, 1H, J=11.4, 5.1 and 1.0 Hz); 4.31 (t, 1H,
J=2.5 Hz); 4.74 (m, 1H); 5.69 (d, 1H, J=2.5 Hz); 7.16 (ddd, 1H,
J=7.1, 5.1 and 1.2 Hz); 7.29-7.40 (m, 6H); 7.54.about.7.58 (m, 2H);
7.74 (d, 1H, J=8.3 Hz); 7.78 (d, 1H, J=8.0 Hz); 8.25.about.8.28 (m,
1H). .sup.31P NMR (CDCl.sub.3, 162 MHz): .delta. -28.03 (s).
EXAMPLE 44
(S.sub.Fe,R.sub.P)-2-[(2-Methoxyphenyl)phenylphosphino]ferrocenecarboxalde-
hyde [(S.sub.Fe,R.sub.P)-48]
##STR00096##
[0154] A mixture of acetal [(2'S, 4'S,S.sub.Fe,R.sub.P)-46] (4.0 g,
7.5 mmol), p-TsOH.H2O (2.0 g), CH.sub.2Cl.sub.2 (50 mL) and H2O (30
mL) was stirred for 24 h at room temperature. The organic layer was
separated, washed with saturated NaHCO3 solution (20 mL), dried
(MgSO4), and evaporated under reduced pressure to give the crude
product (3.20 g, 100%) as red crystals, which was used directly in
next step. .sup.1H NMR (CDCl.sub.3, 250.13 MHz): .delta. 3.66 (s,
3H); 3.96 (m, 1H); 4.22 (s, 5H); 4.71 (t, 1H, J=2.3 Hz); 5.13 (m,
1H); 6.72 (m, 1H); 6.78.about.6.87 (m, 2H); 7.29 (m, 1H); 7.41 (m,
3H); 7.54 (m, 2H); 10.24 (d, 1H, J=3.3 Hz). .sup.31P NMR
(CDCl.sub.3, 101 MHz): .delta. -34.66 (s).
EXAMPLE 45
(S.sub.Fe,R.sub.P)-2-[(1-Naphthyl)phenylphosphino]ferrocenecarboxaldehyde
[(S.sub.Fe, R.sub.P)-49]
##STR00097##
[0156] A mixture of acetal [(2'S, 4'S,S.sub.Fe,R.sub.P)-46] (4.73
g, 7.5 mmol), p-TsOH.H.sub.2O (2.0 g), CH.sub.2Cl.sub.2 (50 mL) and
H.sub.2O (30 mL) was stirred for 24 h at room temperature. The
organic layer was separated, washed with saturated NaHCO.sub.3
solution (20 mL), dried (MgSO.sub.4), and evaporated under reduced
pressure to give the crude product (3.36 g, 100%) as red crystals,
which was used directly in next step. .sup.1H NMR (CDCl.sub.3,
250.13 MHz): .delta. 4.04 (m, 1H); 4.28 (s, 5H); 4.76 (t, 1H, J=2.3
Hz); 5.17 (m, 1H); 7.02 (m, 1H); 7.29.about.7.48 (m, 6H);
7.52.about.7.59 (m, 2H); 7.80 (t, 2H, J=7.5 Hz); 8.26 (m, 1H);
10.20 (d, 1H, J=3.0 Hz). .sup.31P NMR (CDCl.sub.3, 101 MHz):
.delta. -30.50 (s).
EXAMPLE 46
(S.sub.Fe,R.sub.P,.alpha.S)-2-[(2-Methoxyphenyl)phenylphosphino]-1-[(diphe-
nylphosphinophenyl)]ferrocenemethanol [(S.sub.P,.alpha.S)-51]
##STR00098##
[0158] A suspension of magnesium turnings (63 mg, 2.6 mmol) and
2-bromophenyl)diphenylphosphine 50 (887 mg, 2.6 mmol) in THF (10
mL) was refluxed until magnesium was dissolved (about 30 min). The
resulting Gragnard reagent solution was cooled to -78.degree. C.,
and a solution of
(S.sub.Fe,R.sub.P)-2-[(2-methoxyphenyl)phenylphosphino]ferrocenecarbaoxal-
dehyde [(S.sub.Fe,R.sub.P)-48] (856 mg, 2.0 mmol) in THF (10 mL)
was added slowly via a syringe. After stirring for 5 h at
-78.degree. C., the mixture was allowed to warm to room temperature
and stirred overnight at room temperature. The reaction was
quenched with saturated NH.sub.4Cl solution, and extracted with
CH.sub.2Cl.sub.2 (2.times.20 mL). The combined extracts were washed
with brine (20 mL), dried (MgSO4), and evaporated under reduced
pressure. The residue was purified by flash chromatography
(SiO.sub.2, hexane-EtOAc=6:1) to give yellow crystals (1.297 g,
96%) as a mixture of two diastereomers (.about.9:1). Major product:
.sup.1H NMR (CDCl.sub.3, 250 MHz): .delta. 2.91 (br. s, 1H), 3.57
(m, 1H), 3.59 (s, 3H), 4.05 (m, 1H), 4.14 (t, 1H, J=2.4 Hz), 4.18
(s, 5H), 4.22 (m, 1H), 6.48.about.4.56 (m, 2H), 6.68.about.6.80 (m,
2H), 7.02.about.7.37 (m, 13H); 7.49.about.7.58 (m, 2H), 7.67 (m,
1H). .sup.31P NMR (CDCl.sub.3, 101 MHz): .delta. -18.69 (d, J=14.6
Hz), .about.32.85 (d, J=14.6 Hz).
EXAMPLE 47
(S.sub.Fe,R.sub.P,.alpha.S)-2-[(1
Naphthyl)phenylphosphino]-1-[.alpha.-[(diphenylphosphinophenyl)]ferrocene-
methanol[(S.sub.Fe,R.sub.P,.alpha.S)-52]
##STR00099##
[0160] A suspension of magnesium turnings (63 mg, 2.6 mmol) and
2-bromophenyl)diphenylphosphine 50 (887 mg, 2.6 mmol) in THF (10
mL) was refluxed until magnesium was dissolved (about 30 min). The
resulting Gragnard reagent solution was cooled to -78.degree. C.,
and a solution of
(S.sub.Fe,R.sub.P-2-[(1-naphthyl)phenylphosphino]ferrocenecarbaoxaldehyde
[(S.sub.Fe,R.sub.P)-49] (897 mg, 2.0 mmol) in THF (10 mL) was added
slowly via a syringe. After stirring for 5 h at -78.degree. C., the
mixture was allowed to warm to room temperature and stirred
overnight at room temperature. The reaction was quenched with
saturated NH.sub.4Cl solution, and extracted with CH.sub.2Cl.sub.2
(2.times.20 mL). The combined extracts were washed with brine (20
mL), dried (MgSO.sub.4), and evaporated under reduced pressure. The
residue was purified by flash chromatography (SiO.sub.2,
hexane-EtOAc=6:1) to give yellow crystals (1.322 g, 93%) as a
mixture of two diastereomers (.about.9:1). Major product: .sup.1H
NMR (CDCl.sub.3, 250 MHz): .delta. 2.39 (br. s, 1H), 3.66 (m, 1H),
4.24 (s, 5H), 4.29 (t, 1H, J=2.4 Hz), 4.57 (m, 1H), 4.22 (m, 2H),
6.40.about.4.49 (m, 3H), 6.61.about.6.67 (m, 2H), 6.83.about.7.01
(m, 4H); 7.10.about.7.59 (m, H), 7.75 (br. D, 1H, J=7.8 Hz), 8.28
(m, 1H). .sup.31P NMR (CDCl.sub.3, 101 MHz): .delta. -18.54 (d,
J=21.0 Hz), -29.56 (d, J=21.0 Hz).
EXAMPLE 48
(S.sub.Fe,R.sub.P,.alpha.S)-2-[(2-Methoxyphenyl)phenylphosphino]-1-[.alpha-
.-methoxy-(2-diphenylphosphinophenylmethyl)]ferrocene[(S.sub.Fe,R.sub.P,.a-
lpha.S)-53]
##STR00100##
[0162] To a suspension of KH (30%,174 mg, 1.3 mmol washed with
hexane) in THF (10 mL) was added alcohol [(S.sub.P,.alpha.S)-51]
(690 g, 1.0 mmol) at 0.degree. C. After stirring for 2 h at
0.degree. C., iodomethane (68 uL, 1.1 mmoL) was added via a
syringe, then the mixture was stirred for 2 h at 0.degree. C. The
reaction was quenched with MeOH (0.5 mL), and the solvents were
removed under reduced pressure. The residue was dissolved in
CH.sub.2Cl.sub.2 (20 mL), washed with water (10 mL) and brine (10
mL), dried (MgSO.sub.4), and evaporated under reduced pressure. The
residue was purified by flash chromatography (SiO.sub.2,
hexane-EtOAc=10:1) to give yellow crystals (463 mg, 66%). .sup.1H
NMR (CDCl.sub.3, 250 MHz): .delta. 2.82 (s, 3H), 3.50 (m, 1H), 3.57
(s, 3H), 4.11 (t, 1H, J=2.3 Hz), 4.17 (s, 5H), 4.19 (m, 1H), 5.79
(d, 1H, J=6.8 Hz), 6.54.about.6.64 (m, 2H), 6.69 (m, 1H), 6.84
(ddd, 1H, J=7.8, 4.3 and 1.5 Hz), 7.02.about.7.37 (m, 12H), 7.52
(m, 2H), 7.66 (m, 1H); .sup.31P NMR (CDCl.sub.3, 101 MHz): .delta.
-18.44 (d, J=18.7 Hz), -31.19 (d, J=18.7 Hz).
EXAMPLE 49
(S.sub.Fe,.alpha.S)-2-Bromo-1-[.alpha.-(2-diphenylphosphinophenyl)]ferroce-
nemethanol [(S.sub.Fe,.alpha.S)-55]
##STR00101##
[0164] A suspension of Mg (729 mg, 30 mmol) in THF (10 mL) was
added dropwise a solution of 2-bromophenyldiphenylphosphine (50)
(9.42 g, 27.6 mmol) in THF (30 mL) at about 50.degree. C. After
addition, the mixture was refluxed for 1 h, cooled room
temperature, and added to a solution of
(S.sub.Fe)-2-bromoferrocenecarboxaldehyde [(S.sub.Fe)-54](6.74 g,
23 mmol) in Et.sub.2O (20 mL) at -78.degree. C. After stirring for
6 h at -78.degree. C., the mixture was warmed to room temperature,
and stirred overnight at room temperature. The reaction was
quenched with saturated NH.sub.4Cl solution (50 mL), and diluted
with EtOAc (100 mL). The organic layer was separated, washed with
brine (50 mL), dried (Na.sub.2SO.sub.4), and evaporated under
reduced pressure. The residue was purified by chromatography
(SiO.sub.2, hexane-EtOAc=5:1) to give yellow crystals (12.51 g,
98%) as a single diastereomer. .sup.1H NMR (CDCl.sub.3, 250 MHz):
.delta. 2.67 (dd, 1H, J=3.5 and 2.0 Hz), 4.04 (t, 1H, J=2.5 Hz),
4.18 (m, 1H), 4.27 (s, 5H), 4.40 (m, 1H), 6.47 (dd, 1H, J=6.5 and
3.5 Hz), 7.00 (m, 1H), 7.18 (m, 1H), 7.15.about.7.37 (m, 12H);
.sup.31P NMR (CDCl.sub.3, 101 MHz): .delta. -17.30.
EXAMPLE 50
(S.sub.Fe,.alpha.S)-2-Bromo-1-[.alpha.-methoxy-(2-diphenylphosphinophenylm-
ethyl)]ferrocene[(S.sub.Fe,.alpha.S)-56]
##STR00102##
[0166] To a suspension of KH (30%, 3.75 g, 28.1 mmol), washed with
hexane) in THF (20 mL) was added a solution of
(S.sub.P,.alpha.S)-2-Bromo-1-[.alpha.-(2-diphenylphosphinophenyl)]ferroce-
nemethanol [(S.sub.Fe,.alpha.S)-55] (12.00 g, 21.6 mmol) in THF
(180 mL) at 0.degree. C. After stirring for 2 h at 0.degree. C.,
iodomethane (1.48 mL, 23.8 mmoL) was added via a syringe, then the
mixture was stirred for 1 h at 0.degree. C. The reaction was
quenched with MeOH (5 mL), and the solvents were removed under
reduced pressure. The residue was dissolved in EtOAc (150 mL),
washed with water (100 mL) and brine (10o mL), dried (MgSO.sub.4),
and evaporated under reduced pressure. The residue was purified by
flash chromatography (SiO.sub.2, hexane-EtOAc=5:1) to give yellow
crystals (12.10 g, 98%). .sup.1H NMR (CDCl.sub.3, 250 MHz): .delta.
3.29 (s, 3H), 3.96 (t, 1H, J=2.5 Hz), 4.01 (m, 1H), 4.27 (s, 5H),
4.33 (m, 1H), 6.09 (d, 1H, J=7.8 Hz), 7.04 (m, 1H), 7.15.about.7.37
(m, 12H), 7.44 (m, 1H); .sup.31P NMR (CDCl.sub.3, 101 MHz): .delta.
-18.46.
EXAMPLE 51
(S.sub.Fe,S.sub.P,.alpha.S)-2-[(2-Methoxyphenyl)phenylphosphino]-1-[.alpha-
.-methoxy-(2-diphenylphosphinophenylmethyl)]ferrocene[(S.sub.Fe,S.sub.P,.a-
lpha.S)-57]
##STR00103##
[0168] To a solution of bromide [(S.sub.Fe,.alpha.S)-56] (2.85 g, 5
mmol) in THF (30 mL) was added slowly 1.7 M t-BuLi (6.5 mL, 11
mmol) via a syringe at -78.degree. C. After stirring for 10 min at
-78.degree. C., PhPCl.sub.2 (746 uL, 5.5 mmoL) was added via a
syringe, After stirring for 30 min at -78.degree. C., the mixture
was warmed to room temperature and stirred for 1 h at room
temperature. the mixture was cooled to -78.degree. C. again, and a
suspension of o-AnLi [prepared from 2-bromoanisole (805 uL, 6.5
mmol) and 1.7 M t-BuLi (7.6 mL, 13 mmol) in Et.sub.2O (30 mL) at
-78.degree. C.] was added via a cannula, then the mixture was
stirred overnight at -78.degree. C. to room temperature. The
reaction was quenched with water (20 mL), The organic layer was
separated, washed with brine (30 mL), dried (MgSO.sub.4), and
evaporated under reduced pressure. The residue was purified by
flash chromatography (SiO.sub.2, hexane-EtOAc=10:1) to give yellow
crystals (3.21 g, 91%) as a single diastereomer. .sup.1H NMR
(CDCl.sub.3, 250 MHz): .delta. 2.71 (s, 3H), 3.67 (m, 1H), 3.90 (m,
1H), 3.96 (s, 3H), 4.06 (t, 1H, J=2.3 Hz), 4.22 (s, 5H), 5.52 (d,
1H, J=6.5 Hz), 6.80.about.6.98 (m, 4H), 7.08.about.7.36 (m, 14H),
7.76 (m, 1H); .sup.31P NMR (CDCl.sub.3, 101 MHz): .delta. -17.98
(d, J=10.0 Hz), -33.15 (d, J=10.0 Hz).
EXAMPLE 52
(S.sub.Fe,S.sub.P,.alpha.S)-2-[(1-Naphthyl)phenylphosphino]-1-[.alpha.-met-
hoxy-(2-diphenylphosphinophenylmethyl)]ferrocene[(S.sub.Fe,S.sub.P,.alpha.-
S)-58] and
(S.sub.Fe,R.sub.P,.alpha.S)-2-[(1-Naphthyl)phenylphosphino]-1-[-
.alpha.-methoxy-(2-diphenylphosphinophenylmethyl)]ferrocene[(S.sub.Fe,R.su-
b.P,.alpha.S)-59]
##STR00104##
[0170] To a solution of bromide [(S.sub.Fe,.alpha.S)-56] (2.85 g, 5
mmol) in THF (30 mL) was added slowly 1.7 M t-BuLi (6.5 mL, 11
mmol) via a syringe at -78.degree. C. After stirring for 10 min at
-78.degree. C., PhPCl.sub.2 (746 uL, 5.5 mmoL) was added via a
syringe, After stirring for 30 min at -78.degree. C., the mixture
was warmed to room temperature and stirred for 1 h at room
temperature. The mixture was cooled to -78.degree. C. again, and a
suspension of o-AnLi [prepared from 1-bromonaphthalene (900 uL, 6.5
mmol) and 1.7 M t-BuLi (7.6 mL, 13 mmol) in Et.sub.2O (30 mL) at
-78.degree. C.] was added via a cannula, then the mixture was
stirred overnight at -78.degree. C. to room temperature. The
reaction was quenched with water (20 mL), The organic layer was
separated, washed with brine (30 mL), dried (MgSO.sub.4), and
evaporated under reduced pressure. The residue was purified by
flash chromatography (SiO.sub.2, hexane-EtOAc=10:1) to give yellow
crystals (3.30 g, 91%) as a mixture of two diastereomers (ratio:
.about.9:1), which was recrystallised from hexane to give pure
major product [(S.sub.Fe,S.sub.P,.alpha.S)-58] (2.83 g, 78%) as
yellow crystals. The mother liquor was concentrated, and the
residue was recrystallized from MeOH to afford pure minor product
[(S.sub.Fe,R.sub.P,.alpha.S)-59] (217 mg, 6%) as yellow crystals.
Major product [(S.sub.Fe,S.sub.P,.alpha.S)-58]: .sup.1H NMR
(CDCl.sub.3, 250 MHz): .delta.2.96 (s, 3H), 3.74 (m, 1H), 3.84 (s,
5H), 4.13 (t, 1H, J=2.5 Hz), 4.20 (m, 1H), 6.04 (d, 1H, J=7.3 Hz),
6.89.about.7.41 (m, 20H), 7.55 (ddd, 1H, J=58.0, 6.8 and 1.3 Hz),
7.64 (dd, 1H, J=6.8 and 1.5 Hz), 7.69 (ddd, 1H, J=5.3, 3.5 and 1.7
Hz), 7.89 (t, 2H, J=8.0 Hz), 9.32 (dd, 1H, J=7.5 and 6.8 Hz).
.sup.31P NMR (CDCl.sub.3, 101 MHz): .delta. -18.83 (d, J=21.3 Hz),
-35.08 (d, J=21.3 Hz). Minor product
[(S.sub.Fe,R.sub.P,.alpha.S)-59]: .sup.1H NMR (CDCl.sub.3, 250
MHz): .delta. 2.73 (s, 3H), 3.61 (m, 1H), 4.21 (t, 1H, J=2.5 Hz),
4.22 (s, 5H), 4.28 (m, 1H), 5.86 (d, 1H, J=7.3 Hz), 6.67 (ddd, 1H,
J=7.8, 4.3 and 1.3 Hz), 6.79.about.7.61 (m, 23H), 7.75 (br. d, 1H,
J=8.0 Hz), 8.29 (m, 1H). .sup.31P NMR (CDCl.sub.3, 101 MHz):
.delta. -18.52 (d, J=18.4 Hz), -27.69 (d, J=18.4 Hz).
EXAMPLE 53
(S.sub.Fe,R.sub.P)-2-[(2-Methoxyphenyl)phenylphosphino]ferrocenemethanol[(-
S.sub.Fe, R.sub.P)-60]
##STR00105##
[0172] To a solution of aldehyde [(S.sub.Fe,R.sub.P)-48] (856 mg,
2.0 mmol) in THF (10 mL) was added NaBH.sub.4 (38 mg, 1.0 mmol) at
0.degree. C., then MeOH (2 mL) was added. After stirring for 2 h at
0.degree. C., the mixture was warmed to room temperature and
stirred overnight at room temperature. The reaction was quenched
with saturated NH.sub.4Cl solution (5 mL), and diluted with EtOAc
(10 mL). The organic layer was separated, washed with brine (10
mL), dried (MgSO.sub.4), and evaporated under reduced pressure to
give the crude product (857 mg, 100%) as yellow crystals, which was
used directly in next step. .sup.1H NMR (CDCl.sub.3, 250 MHz):
.delta. 3.63 (m, 1H), 3.66 (s, 3H), 4.10 (s, 5H), 4.29 (t, 1H,
J=2.0 Hz), 4.41 (d, 1H, J=12.5 Hz), 4.53 (m, 1H), 4.58 (dd, 1H,
J=12.5 and 2.0 Hz), 6.77.about.6.90 (m, 3H), 7.28 (m, 1H),
7.34.about.7.41 (m, 3H), 7.48.about.7.55 (m, 2H). .sup.31P NMR
(CDCl.sub.3, 101 MHz): .delta. -35.05.
EXAMPLE 54
(S.sub.Fe,R.sub.P)-2-[(1-Naphthyl)phenylphosphino]ferrocenemethanol[(S.sub-
.Fe,R.sub.P)-61]
##STR00106##
[0174] To a solution of aldehyde [(S.sub.Fe,R.sub.P)-49] (897 mg,
2.0 mmol) in THF (10 mL) was added NaBH.sub.4 (38 mg, 1.0 mmol) at
0.degree. C., then MeOH (2 mL) was added. After stirring for 2 h at
0.degree. C., the mixture was warmed to room temperature and
stirred overnight at room temperature. The reaction was quenched
with saturated NH.sub.4Cl solution (5 mL), and diluted with EtOAc
(10 mL). The organic layer was separated, washed with brine (10
mL), dried (MgSO.sub.4), and evaporated under reduced pressure to
give the crude product (900 mg, 100%) as yellow crystals, which was
used directly in next step. .sup.1H NMR (CDCl.sub.3, 250 MHz):
.delta. 3.71 (m, 1H), 4.16 (s, 5H), 4.36 (t, 1H, J=2.5 Hz), 4.41
(d, 1H, J=12.5 Hz), 4.54 (dd, 1H, J=12.5 and 1.3 Hz), 4.58 (m, 1H),
7.11 (ddd, 1H, J=7.0, 4.5 and 1.3 Hz), 7.30.about.7.57 (m, 8H),
7.80 (m, 2H), 8.26 (m, 1H). .sup.31P NMR (CDCl.sub.3, 101 MHz):
.delta. -31.14.
EXAMPLE 55
(S.sub.Fe,R.sub.P)-2-[(2-Methoxyphenyl)phenylphosphino]ferrocenemethanol
acetate[(S.sub.Fe,R.sub.P)-62]
##STR00107##
[0176] A solution of alcohol [(S.sub.Fe,R.sub.P)-60] (857 mg, 2.0
mmol), Ac.sub.2O (2 mL) and pyridine (2 mL) in CH.sub.2Cl.sub.2 (10
mL) was stirred overnight at room temperature. The volatile matters
were removed under reduced pressure below 35.degree. C. to give the
crude product (880 mg, 100%) as yellow crystals, which was used
directly in next step. .sup.1H NMR (CDCl.sub.3, 250 MHz): .delta.
1.62 (s, 3H), 3.64 (s, 4H, overlapped), 4.10 (s, 5H), 4.30 (t, 1H,
J=2.5 Hz), 4.54 (m, 1H), 5.01 (d, 1H, J=12.0 Hz), 5.12 (dd, 1H,
J=12.0 and 2.3 Hz), 6.77 (m, 2H), 6.83 (t, 1H, J=7.5 Hz), 7.25 (m,
1H), 7.37 (m, 3H), 7.51 (m, 2H). .sup.31P NMR (CDCl.sub.3, 101
MHz): .delta. 34.60.
EXAMPLE 56
(S.sub.Fe,R.sub.P)-2-[(1-Naphthyl)phenylphosphino]ferrocenemethanol
acetate [(S.sub.Fe, R.sub.P)-63]
##STR00108##
[0178] A solution of alcohol [(S.sub.Fe,R.sub.P)-61] (900 mg, 2.0
mmol), Ac.sub.2O (2 mL) and pyridine (2 mL) in CH.sub.2Cl.sub.2 (10
mL) was stirred overnight at room temperature. The volatile matters
were removed under reduced pressure below 35.degree. C. to give the
crude product (983 mg, 100%) as yellow crystals, which was used
directly in next step. .sup.1H NMR (CDCl.sub.3, 250 MHz): .delta.
1.46 (s, 3H), 3.74 (m, 1H), 4.15 (s, 5H), 4.38 (t, 1H, J=2.5 Hz),
4.59 (m, 1H), 5.00 (d, 1H, J=1.3.5 Hz), 7.28.about.7.45 (m, 5H),
7.54 (m, 1H), 7.69 (tt, 1H, J=7.8 and 1.8 Hz), 7.78 (m, 2H), 8.23
(m, 1H), 8.64 (m, 2H). .sup.31P NMR (CDCl.sub.3, 101 MHz): .delta.
-30.85.
EXAMPLE 57
(S.sub.Fe,R.sub.P)-1-[(Dicyclohexylphosphino)methyl]-2-[(2-methoxyphenyl)p-
henylphosphino]ferrocene[(S.sub.Fe,R.sub.P)-64]
##STR00109##
[0180] A solution of (S.sub.Fe,R.sub.P)-62 (472 mg, 1.0 mmol) and
dicyclohexylphosphine (243 uL, 1.2 mmol) in acetic acid (3 mL) was
stirred for 7 days at room temperature, and poured into 10%
K.sub.2CO.sub.3 aqueous solution (60 mL) with stirring, extracted
with Et.sub.2O (2.times.25 mL). The combined ether layers were
dried (MgSO.sub.4) and concentrated. The residue was purified by
chromatography (SiO.sub.2, hexane-EtOAc=9:1) to afford the title
compound (573 mg, 94%) as orange crystals. .sup.1H NMR (CDCl.sub.3,
250.13 MHz): .delta. 0.99.about.1.79 (m, 22H), 2.56 (br. d, 1H,
J=12.5 Hz), 2.73 (br. d, 1H, J=12.5 Hz), 3.58 (m, 1H), 4.00 (s,
5H), 4.20 (m, 1H), 4.57 (m, 1H); 4.32 (m, 1H), 6.74.about.7.58 (m,
9H); .sup.31P NMR (CDCl.sub.3, 101.25 MHz): .delta.-2.93;
-35.19.
EXAMPLE 58
(S.sub.Fe,R.sub.P)-1-[(Dicyclohexylphosphino)methyl]-2-[(1-naphthyl)phenyl-
phosphino]ferrocene[(S.sub.Fe,R.sub.P)-65]
##STR00110##
[0182] A solution of (S.sub.Fe,R.sub.P)-63 (492 mg, 1.0 mmol) and
dicyclohexylphosphine (243 uL, 1.2 mmol) in acetic acid (3 mL) was
stirred for 7 days at room temperature, and poured into 10%
K.sub.2CO.sub.3 aqueous solution (60 mL) with stirring, extracted
with Et.sub.2O (2.times.25 mL). The combined ether layers were
dried (MgSO.sub.4) and concentrated. The residue was purified by
chromatography (SiO.sub.2, hexane-EtOAc=9:1) to afford the title
compound (599 mg, 95%) as orange crystals. .sup.1H NMR (CDCl.sub.3,
250.13 MHz): .delta. 0.83.about.1.76 (m, 22H), 2.57 (dm, 1H, J=12.5
Hz), 2.70 (dm, 1H, J=12.5 Hz), 3.67 (m, 1H), 4.06 (s, 5H), 4.27 (t,
1H, J=2.5 Hz), 4.60 (m, 1H); 7.12 (m, 1H), 7.31.about.7.82 (m,
10H); 8.28 (m, 1H). .sup.31P NMR (CDCl.sub.3, 101.25 MHz): .delta.
-2.19; -31.85.
EXAMPLE 59
(S.sub.C,S.sub.Fe,R.sub.P)-67
##STR00111##
[0184] To a solution of (S)-66 (1.56 g, 5 mmol) and TMEDA (1.0 mL,
6.5 mmol) in Et.sub.2O (50 mL) was added 2.5 M n-BuLi (2.6 mL, 6.5
mmol) at -78.degree. C., After stirring for 3 h at -78.degree. C.,
PhPCl.sub.2 (0.95 mL, 7.0 mmol) was added, After stirring for 20
min at -78.degree. C., the mixture was warmed to room temperature
and stirred for 1.5 h at room temperature. The mixture was cooled
to -78.degree. C. again, and a suspension of 1-NpLi [prepared from
1-bromonaphthalene (1.39 mL, 10 mmol) and 1.7 M t-BuLi (11.8 mL, 20
mmol) in Et.sub.2O (40 mL) at -78.degree. C.] was added via a
cannula. The mixture was stirred and warmed to room temperature
overnight. The reaction was quenched by water (40 mL). The organic
layer was separated, washed with brine (40 mL), dried (MgSO.sub.4),
and concentrated. The residue was purified by chromatography
(SiO.sub.2, EtOAc-hexane=1:5.about.1:3) to give the product (2.25
g, 85%) as an orange crystals. .sup.1H NMR and .sup.31P NMR
analysis show the de is about 9:1. Major product: .sup.1H NMR
(CDCl.sub.3, 400.13 MHz): .delta. 0.58 (d, 3H, J=6.7 Hz); 0.73 (d,
3H, J=6.7 Hz); 1.58 (m, 1H), 3.45.about.3.52 (m, 2H), 3.61 (m, 1H),
3.78 (m, 1H), 4.29 (s, 5H); 4.44 (t, 1H, J=2.6 Hz); 5.05 (m, 1H);
7.08 (dd, 1H, J=7.0 and 4.4 Hz); 7.24.about.7.48 (m, 8H); 7.74 (d,
1H, J=8.0 Hz); 7.80 (d, 1H, J=8.0 Hz); 8.37 (dd, 1H, J=8.3 and 4.3
Hz). .sup.31P NMR (CDCl.sub.3, 162 MHz): .delta.-23.52 (s).
REFERENCES
[0185] 1. T. Hayashi, in Ferrocenes, (Eds.: A. Togni, T. Hayashi),
VCH, Weinheim, 1995, p. 105. [0186] 2. 2. Togni, A.; Breutel, C.;
Schnyder, A.; Spindler, F.; Landert, H.; Tijani, A. J. Am. Chem.
Soc. 1994, 116, 4062. [0187] 3. 3. a. H. U. Blaser, W. Brieden, B.
Pugin, F. Spindler, M. Studer, A. Togni, Topics in Catalysis 2002,
19, 3; b. H. U. Blaser, F. Spindler, M. Studer, Applied Catal. A:
General 2001, 221, 119. [0188] 4. 4. McGarrity, J.; Spindler, F.;
Fuchs, R.; Eyer, M. (LONZA AG), EP-A 624587 A2, 1995; Chem. Abstr.
1995, 122, P81369q. [0189] 5. 5. a. Blaser, H.-U. Adv. Synth.
Catal. 2002, 344, 17. b. Blaser, H.-U.; Buser, H.-P.; Coers, K.;
Hanreich, R.; Jaleft, H.-P.; Jelsch, E.; Pugin, B.; Schneider,
H.-D.; Spindler, F.; Wegmann, A. Chimia 1999, 53, 275. [0190] 6. 6.
a. N. W. Boaz, S. D. Debenham, E. B. Mackenzie, S. E. Large, Org.
Lett. 2002, 4, 2421. b. Boaz, N. W.; Debenham, S. D. US
2002/0065417 (2002) [0191] 7. a) T. Ireland, G. Grossheimann, C.
Wieser-Jeunesse, P. Knochel, Angew. Chem. Int. Ed. 1999, 38, 3212.
b) T. Ireland, K. Tappe, G. Grossheimann, P. Knochel, Chem. Eur. J.
2002, 8, 843; [0192] 8. a) M. Lotz, K. Polborn, P. Knochel, Angew.
Chem. Int. Ed. 2002, 41, 4708. b) K. Tappe; P. Knochel,
Tetrahedron: Asymmetry 2004, 15, 12; c) M. Lotz, P. Knochel, A.
Monsees, T. Riermeier, R. Kadyrov, J. J. Almena Perea, Ger. Pat.
No. DE 10219490 (Degussa AG). [0193] 9. a) T. Sturm, L. Xiao, W.
Weissensteiner, Chimia 2001, 55, 688; b) W. Weissensteiner, T.
Sturm, F. Spindler, Adv. Synth. Catal. 2003, 345, 160; c)
Weissensteiner, T. Sturm, F. Spindler, US2003212284. [0194] 10. a.
Perea, A. J. J.; Bomer, A.; Knochel, P. Tetrahedron Lett. 1998, 39,
8073. b. Perea, A. J. J.; Lotz, M.; Knochel, P. Tetrahedron:
Asymmetry 1999, 10, 375. c. Lotz, M.; Ireland, T.; Perea, A. J. J.;
Knochel, P. Tetrahedron: Asymmetry 1999, 10, 1839. d. Knochel, P.;
Perea, A. J. J.; Drauz, K.; Klement, I. U.S. Pat. No. 6,284,925
(2001). [0195] 11. (a) Sawamura, M.; Hamashima, H.; Sugawara, M.;
Kuwano, N.; Ito, Y. Organometallics 1995, 14, 4549. (b) Sawamura,
M.; Kuwano, R.; Ito, Y. J. Am. Chem. Soc. 1995, 117, 9602. (c)
Kuwano, R.; Sawamura, M.; Ito, Y. Tetrahedron: Asymmetry 1995, 6,
2521. (d) Kuwano, R.; Okuda, S.; Ito, Y. Tetrahedron: Asymmetry
1998, 9, 2773. (e) Kuwano, R.; Okuda, S.; Ito, Y. J. Org. Chem.
1998, 63, 3499. (f) Kuwano, R.; Ito, Y. J. Org. Chem. 1999, 64,
1232. (g) Kuwano, R.; Sato, K.; Kurokawa, T.; Karube, D.; Ito, Y.
J. Am. Chem. Soc. 2000, 122, 7614. [0196] 12. a) Kang, J.; Lee, J.
H.; Ahn, S. H.; Chol, J. S. Tetrahedron Lett. 1998, 39, 5523. b)
Kang, J.; Lee, J. H.; Kim, J. B.; Kim, G. J. Chirality 2000, 12,
378. [0197] 13. a) Jendralla, H.; Paulus, E. Synleft, 1997, 471. b)
Jendralla, J. H. U.S. Pat. No. 5,856,540 (1999) [0198] 14. a)
Argouarch, G.; Samuel, O.; Kagan, H. B. Eur. J. Org. Chem. 2000,
2891. b) Argouarch, G.; Samuel, O.; Riant, O.; Daran, J.-C.; Kagan,
H. B. Eur. J. Org. Chem. 2000, 2893. [0199] 15. Marinetti, A.;
Labrue, F.; Gene t, J.-P. Synlett 1999, 1975. [0200] 16. Berens,
U.; Burk, M. J.; Gerlach, A.; Hems, W. Angew. Chem., Int. Ed. Engl.
2000, 39, 1981. [0201] 17. You, J.; Drexler, H.-J.; Zhang, S.;
Fischer, C.; Heller, D. Angew. Chem., Int. Ed. EngI. 2003, 42, 913.
[0202] 18. Maienza, F.; Wo{umlaut over ( )}rle, M.; Steffanut, P.;
Mezzetti, A. Organometallics 1999, 18, 1041. [0203] 19. (a)
Nettekoven, U.; Widhalm, M.; Kamer, P. C. J.; van Leeuwen, P. W. N.
M. Tetrahedron: Asymmetry 1997, 8, 3185. (b) Nettekoven, U.; Kamer,
P. C. J.; van Leeuwen, P. W. N. M.; Widhalm, M.; Spek, A. L.; Lutz,
M. J. Org. Chem. 1999, 64, 3996. [0204] 20. Liu, D.; Li, W.; Zhang,
X. Org. Lett. 2002, 4, 4471. [0205] 21. Xiao, D.; Zhang, X. Angew.
Chem., Int. Ed. EngI. 2001, 40, 3425. [0206] 22. a) M. T. Reetz, A.
Gosberg, R. Goddard, S.-H. Kyung, Chem. Commun. 1998, 2077; b) M.
T. Reetz, A. Gosberg, WO 0014096, 1998 (assigned to
Studiengesellschaft Kohle MBH); [0207] 23. a. Nettekoven, U.;
Widhalm, M.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Mereiter,
K.; Lutz, M.; Spek, A. L. Organometallics 2000, 19, 2299. b.
Nettekoven, U.; Kamer, P. C. J.; Widhalm, M.; van Leeuwen, P. W. N.
M. Organometallics 2000, 19, 4596. c. Nettekoven, U.; Widhalm, M.;
Kalchhauser, H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Lutz,
M.; Spek, A. L. J. Org. Chem. 2001, 66, 759-770. [0208] 24.
Barbaro, P.; Bianchini, C.; Giambastiani, G.; Togni, A. Chem.
Commun. 2002, 2672. [0209] 25. (a) Marquarding, D.; Klusacek, H.;
Gokel, G.; Hoffmann, P.; Ugi, I. J. Am. Chem. Soc. 1970, 92, 5389.
(b) Marquarding, D.; Klusacek, H.; Gokel, G.; Hoffmann, P.; Ugi, I.
Angew. Chem. Int. Ed. Engl. 1970, 9, 371. (c) Hayashi, T.;
Yamamoto, K.; Kumada, M. Tetrahedron Lett. 1974, 15, 405. (d)
Hayashi, T.; Mise, T.; Fukushima, M.; Kagotani, M.; Nagashima, N.;
Hamada, Y.; Matsumoto, A.; Kawakami, S.; Konishi, M. M.; Yamamoto,
K.; Kumada, M. Bull. Chem. Chem. Soc. Jpn. 1980, 53, 1138 [0210]
26. Riant, O.; Argouarch, G.; Guillaneux, D.; Samuel, O.; Kagan, H.
B. J. Org. Chem. 1998, 63, 3511. [0211] 27. (a) Riant, O.; Samuel,
O.; Flessner, T.; Taudien, S.; Kagan, H. B. J. Org. Chem. 1997, 62,
6733. (b) Riant, O.; Samuel, O.; Kagan, H. B. J. Am. Chem. Soc.
1993, 115, 5835. [0212] 28. (a) Richards, J.; Damalidis, T.; Hibbs
D. E.; Hursthouse, M. B. Synlett 1995, 74. (b) Sammakai, T.; Latham
H. A.; Schaad, D. R. J. Org. Chem. 1995, 60, 10. (c) Nishibayashi,
Y.; Uemura, S. Synlett 1995, 79. (d) Sammakai, T.; Latham, H. A. J.
Org. Chem. 1995, 60, 6002. [0213] 29. Ganter, C.; Wagner, T. Chem.
Ber. 1995, 128, 1157. [0214] 30. (a) Enders, D.; Peters, R.;
Lochtman, R.; Runsink, J. Synlett 1997, 1462. (b) Enders, D.;
Peters, R.; Lochtman, R.; Runsink, J. Eur. J. Org. Chem. 2000,
2839. [0215] 31. Lotz, M.; Ireland T.; Tappe, K.; Knochel, P.
Chirality, 2000, 12, 389. [0216] 32. Kitzler, R.; Xiao, L.;
Weissensteiner, W. Tetrahedron: Asymmetry 2000, 11, 3459. [0217]
33. Widhalm, M.; Mereiter, K.; Bourghida, M. Tetrahedron: Asymmetry
1998, 9, 2983. [0218] 34. Nishibayashi, Y.; Arikawa, Y.; Ohe, K.;
Uemura, S. J. Org. Chem. 1996, 61, 1172. [0219] 35. (a) Tsukazaki,
M.; Tinkl, M.; Roglans, A.; Chapell, B. J.; Taylor, N. J.;
Snieckus, V. J. Am. Chem. Soc. 1996, 118, 685. (b) Jendralla, H.;
Paulus, E. Synleft 1997, 471. [0220] 36. Price, D.; Simpkins, N. S.
Tetrahedron Lett. 1995, 36, 6135.
* * * * *