U.S. patent application number 14/270793 was filed with the patent office on 2014-08-28 for iron(ii) catalysts containing diimino-diphosphine tetradentate ligands and their synthesis.
This patent application is currently assigned to THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO. The applicant listed for this patent is THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO. Invention is credited to FRIEDERIKE FREUTEL, PARASEKEVI OLYMPIA LAGADITIS, NILS MEYER, ALEXANDRE MIKHAILINE, ROBERT H. MORRIS, CHRISTINE SUI-SENG.
Application Number | 20140243543 14/270793 |
Document ID | / |
Family ID | 42231838 |
Filed Date | 2014-08-28 |
United States Patent
Application |
20140243543 |
Kind Code |
A1 |
MIKHAILINE; ALEXANDRE ; et
al. |
August 28, 2014 |
IRON(II) CATALYSTS CONTAINING DIIMINO-DIPHOSPHINE TETRADENTATE
LIGANDS AND THEIR SYNTHESIS
Abstract
New hexa-coordinate iron (II) complexes comprising compounds of
formula (I) are described. These compounds comprise a tetradentate
ligand with donor atoms comprising nitrogen and phosphorus. These
complexes are shown for the first time to be useful catalysts for
the hydrogenation of ketones, aldehydes, or imines to produce
alcohols or amines, and the asymmetric hydrogenation of prochiral
ketones or imines to produce non-racemic alcohols or amines. The
source of the hydrogen can be hydrogen gas or a hydrogen-donating
molecule such as isopropanol or hydrogen-donating mixture such as
formic acid and an amine depending on the structure of the
catalyst. In certain embodiments, the axial ligands on the catalyst
comprise organonitrile ligands, carbonyl ligands, isonitrile
ligands, or combinations thereof. The catalysts and the preparation
thereof are disclosed. A reaction using phosphine and diamine
precursors that is templated by the iron ion is the preferred route
to the catalysts. ##STR00001##
Inventors: |
MIKHAILINE; ALEXANDRE;
(RICHMOND HILL, CA) ; FREUTEL; FRIEDERIKE;
(WIESBADEN, DE) ; SUI-SENG; CHRISTINE; (TORONTO,
CA) ; MEYER; NILS; (BRUNSBUETTEL, DE) ;
MORRIS; ROBERT H.; (TORONTO, CA) ; LAGADITIS;
PARASEKEVI OLYMPIA; (RICHMOND, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO |
TORONTO |
|
CA |
|
|
Assignee: |
THE GOVERNING COUNCIL OF THE
UNIVERSITY OF TORONTO
TORONTO
CA
|
Family ID: |
42231838 |
Appl. No.: |
14/270793 |
Filed: |
May 6, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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12609955 |
Oct 30, 2009 |
8716507 |
|
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14270793 |
|
|
|
|
61193147 |
Oct 31, 2008 |
|
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Current U.S.
Class: |
556/20 |
Current CPC
Class: |
C07C 29/141 20130101;
C07C 29/145 20130101; C07C 29/145 20130101; C07F 15/025 20130101;
C07F 17/02 20130101; C07F 15/02 20130101; C07C 29/145 20130101;
C07C 29/145 20130101; C07F 9/5022 20130101; C07C 29/145 20130101;
C07C 29/141 20130101; C07C 31/125 20130101; C07C 33/18 20130101;
C07C 33/22 20130101; C07C 33/46 20130101; C07C 33/22 20130101; C07C
33/20 20130101; B01J 31/1805 20130101; C07C 29/145 20130101; B01J
31/2295 20130101; C07F 9/65688 20130101 |
Class at
Publication: |
556/20 |
International
Class: |
B01J 31/22 20060101
B01J031/22 |
Claims
1. (canceled)
2. A hexa-coordinate iron (II) complex comprising a compound of
formula (I): ##STR00096## wherein each R.sup.1 is phenyl; A is
##STR00097## each R.sup.4 is H; R.sup.5, R.sup.6, R.sup.7 and
R.sup.8, together with the carbon atoms to which they are attached,
may combine to form a group selected from ##STR00098## each of
which is unsubstituted or is substituted with one or more
substituents selected from the group consisting of C.sub.1-C.sub.8
alkyl, C.sub.1-C.sub.8 alkoxy, and halogen atoms; L.sup.1 is
CH.sub.3CN; L.sup.2 is selected from the group consisting of
CH.sub.3CN, CO and CNtBu; and m is +2.
3. The hexa-coordinate iron (II) complex of claim 2, wherein both
of the chiral carbon atoms denoted by asterisks have an R
configuration, or have an S configuration.
4. A hexa-coordinate iron (II) complex comprising a compound of
formula (I): ##STR00099## wherein each R.sup.1 is phenyl; A is
selected from: ##STR00100## each R.sup.4 is H; each of R.sup.5 and
R.sup.8 is phenyl, and each of R.sup.6 and R.sup.7 is H; L.sup.1 is
CH.sub.3CN; L.sup.2 is selected from the group consisting of
CH.sub.3CN, CO, and CNtBu; and m is +2 and the iron (II) complex
comprises the anion BPh.sub.4.sup.-.
5. The hexa-coordinate iron (II) complex of claim 4, wherein both
of the chiral carbon atoms denoted by asterisks have an R
configuration, or have an S configuration.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S.
application Ser. No. 12/609,955, filed on Oct. 30, 2009, which
claims the benefit of U.S. Provisional Application No. 61/193,147,
filed on Oct. 31, 2008. The entire contents of each of U.S.
application Ser. No. 12/609,955 and U.S. Provisional Application
No. 61/193,147 are hereby incorporated herein by reference in their
entirety.
TECHNICAL FIELD
[0002] The present invention relates to catalytic materials for
hydrogenation or asymmetric hydrogenation. In particular, the
invention relates to iron (II) complexes containing tetradentate
diimino-diphosphine (P.sub.2N.sub.2) ligands for the catalytic
hydrogenation or asymmetric hydrogenation of carbonyl groups for
use in preparing alcohols or non racemic alcohols, respectively.
Imine groups can similarly be hydrogenated or asymmetrically
hydrogenated to provide amines, or non-racemic amines,
respectively. These alcohols and amine products are important raw
materials in the manufacturing of chemical products,
pharmaceuticals, fragrance and flavours.
BACKGROUND
[0003] Asymmetric hydrogenation is an important method for
generating single enantiomer molecules that include intermediates
and fine chemicals with applications in the pharmaceuticals,
biotechnology, agrochemical, food, flavours, essential oils,
personal care and advanced materials industries. Each enantiomer
may have quite different properties and effectiveness. The use of a
drug molecule as a single enantiomer reduces the risk of negative
effects of a racemate, increases efficacy and accuracy of dosage,
reduces the dosage compared to racemates by one half, with a
subsequent reduction in cost and waste, environmental burden
including agricultural and human waste run-off. This is
particularly true since the US Food and Drug Administration, the
European Committee for Proprietary Medicinal Products and other
regulatory authorities have required characterization of
enantiomers in proposed marketable drug products. Examples of some
of the top selling drug products that are chiral are: Lipitor.TM.,
Zocor.TM., Zyprexa.TM., Norvasc.TM., Procrit.TM., Prevacid.TM.,
Nexium.TM., Plavix.TM., Advair.TM. and Zoloft.TM.. In 2003 the
total global sales for these products amounted to 48.3 billion
dollars.
[0004] In the biotechnology sector the ability to synthesize
enantiomerically pure amino acids, peptides and proteins is of
great value. In the agrochemical business about 25% of the members
of several classes of pesticides and herbicides exist as
enantiomers. Currently the largest scale asymmetric hydrogenation
process is the production of the S enantiomer of
Metalochlor.TM..
[0005] Volatile, enantiomerically pure alcohols are particularly
valuable in the flavours and fragrances industries where each
enantiomer provides a distinctive olfactory sensation. They are
playing an increasingly important role in aromatherapy.
[0006] Single enantiomer helical molecules impart important
optical, electronic and magnetic properties to materials and
nanomaterials with applications in switches, motors, sensors,
polarizers and displays.
[0007] In the hydrogenation of complex molecules, the selectivity
and activity of the process is dependent on the catalyst structure.
This structure must interact with the substrate to provide the
diastereomeric transition state of lower energy that leads to the
required enantiomer.
[0008] Conventional asymmetric hydrogenation catalysts utilize
platinum group metals (PGM) ruthenium, osmium, rhodium, iridium,
palladium or platinum (De Vries et al., "Handbook of Homogeneous
Hydrogenation" Wiley-VCH, volumes 1-3, 2007). Their ability to
activate hydrogen gas toward addition to organic compounds is well
known. However, these metals present potential toxicity problems
and prolonged usage of pharmaceuticals containing traces of these
metals might lead to harmful bio-accumulation. PGM are expensive
and thereby add to the cost of the final product. In addition, they
are in limited supply and will decrease in availability over
time.
[0009] The direct hydrogenation of carbonyl and/or imine groups in
an organic molecule using hydrogen gas is now becoming the
preferred "green" method because no waste is produced and the
separation of product is easier. Hydrogen is expected to be an even
more abundant feedstock as it is used more as a green fuel. In a
complimentary way, the catalytic hydrogenation or asymmetric
hydrogenation of carbonyl and/or imine groups in an organic
molecule by transfer from a hydrogen-donating molecule or mixture
has the advantage of operational simplicity by avoiding the use of
pressurized hydrogen (Gladiali et al., "Asymmetric transfer
hydrogenation: chiral ligands and applications," Chem. Soc. Rev. 35
(2006) pp 226-236).
[0010] The reduction of ketones is one of the fundamental reactions
in the chemistry field and is used in many chemical transformations
towards various products. Asymmetric reduction of the carbonyl
group was achieved in the past using chiral catalysts that are
based on platinum group metals (PGM) such as ruthenium, rhodium,
iridium, palladium or platinum. Usually .sup.iPrOH or H.sub.2 are
used as a reducing agent in those transformations when they are
activated by the metal-catalysts. The activation is normally
produced via the in situ formation of the catalyst from
pre-catalyst by the addition of a strong base.
[0011] Reduction catalysis utilizing molecular hydrogen is more
attractive compared to the reduction with .sup.iPrOH because of the
low price of hydrogen gas, product purification simplicity and
waste elimination. Reduction catalysis by hydrogen transfer from
.sup.iPrOH is preferred when pressurized hydrogen gas is not
available or convenient.
[0012] Chiral alcohols and amines that are produced by the
asymmetric hydrogenation or asymmetric transfer hydrogenation of
ketones and imines, respectively, are extensively used in the
synthesis of pharmaceuticals, agricultural chemicals, fragrances
and materials. A non-limiting list of the examples of such
compounds is presented below:
##STR00002##
[0013] Product 1 can be used in preparation of the (+)-compactin,
an HMG-CoA-reductase inhibitor. Product 2 can be used in the
synthesis of 2,4-diaminoquinazoline derivatives which are possible
SMN2 promoter activators which can be used in the treatment of
spinal muscular atrophy. Product 3 may be used as a synthetic
building block of the highest selling drug Fluoxetine
(Prozac.RTM.). Product 4 may be used as a chiral synthetic
intermediate in preparation of the benzazepine dopamine antagonist
Sch 39 166.
[0014] Although some PGM catalytic systems have enzyme-like
enantioselectivities and activities, their toxicity and high price
make them unattractive for some industrial synthetic
transformations.
[0015] Attempts have been made to solve this problem. For example,
Gao et al. in 1996 in the journal Polyhedron (Gao et al. "Synthesis
and characterization of iron(2+) and ruthenium(2+)
diimino-diphosphine, diamino-diphosphine and diamido-diphosphine
complexes,"Polyhedron 1 (1996), pp. 1241-1251) reported the
synthesis of iron complexes with tetradentate ligands. The use and
application of their iron complexes towards hydrogenation was not
disclosed. They reported the synthesis of two iron complexes with
diphosphinediimine ligands 6 and 7:
trans-[Fe(NCMe).sub.2(6)](ClO.sub.4).sub.2
trans-[Fe(NCMe).sub.2(7)](ClO.sub.4).sub.2.
##STR00003##
[0016] They also reported the iron complex with the
diphosphinediamine ligand 8.
##STR00004##
[0017] Further, Gao et al. in 1996 in the journal Organometallics
(Gao et al., "A ruthenium(ii) complex with a c-2-symmetrical
diphosphine/diamine tetradentate ligand for asymmetric transfer
hydrogenation of aromatic ketones,"Organometallics 15 (1996), pp.
1087-1089) disclosed that ruthenium complexes with the enantiopure
ligands 9 ((R,R)-cyP.sub.2N.sub.2) and 10 are catalysts for the
asymmetric transfer hydrogenation of ketones with the latter
displaying superior activity and selectivity. Rautenstrauch et al.
(Rautenstrauch et al., "Hydrogenation versus Transfer Hydrogenation
of Ketones: Two Established Ruthenium Systems Catalyze Both," Chem.
Eur. J. 9 (2003), pp. 4954-4967; 6,878,852 B2 5/2005 to
Rautenstrauch et al.) showed that similar ruthenium complexes are
active for the hydrogenation and asymmetric hydrogenation of
ketones.
##STR00005##
[0018] Boaz et al. (U.S. Pat. No. 6,690,115 B2 7/2003 to Boaz et
al.; 2006/0135805 A1 to Boaz et al.) made ketone hydrogenation
catalysts based on PG metals such as Ru and Rh in complexes of PNNP
ligands of the type 11. Here the iron is part of the ferrocenyl
substituent on the ligand which is known in the art to provide
selectivity and sometimes activity to a PG metal catalyst.
##STR00006##
[0019] Chen et al. (Chen et al., "Asymmetric transfer hydrogenation
of ketones catalyzed by chiral carbonyl iron systems," Huaxue
Xuebao 62 (2004), pp. 1745-1750) reported an asymmetric transfer
hydrogenation system where one of the compounds 10, 12 or 13 of the
type P--NH--NH--P are added to [HFe.sub.3(CO).sub.11].sup.- to
generate in situ catalysts for the transfer of hydrogen from
isopropanol to ketones but the activity was low and the nature of
the active catalyst was thought to be a cluster containing the
three irons. The structure of this catalyst remains unknown. Other
iron precursors Fe(CO).sub.5 and
[Fe(C.sub.5H.sub.5)(CO.sub.2].sub.2 did not lead to active catalyst
mixtures.
##STR00007##
[0020] Bianchini et al. (Bianchini et al., "Chemoselective
Hydrogen-Transfer Reduction of alpha, beta-Unsaturated Ketones
Catalyzed by Isostructural Iron(II), Ruthenium(II), and Osmium(II)
cis Hydride eta(2)-Dihydrogen Complexes," Organometallics 12
(1993), pp. 3753-3761) reported that iron complexes with a
tetradentate PP.sub.3 ligand were active for the non-asymmetric
hydrogenation of olefins under mild conditions.
[0021] Enthaler et al. (Enthaler et al., "Biomimetic transfer
hydrogenation of ketones with iron porphyrin catalysts," Tet. Lett.
47 (2006), pp. 8095-8099) reported that in situ-generated iron
complexes of achiral porphyrin ligands are somewhat active for the
hydrogenation of ketones but no asymmetric hydrogenation reaction
was possible because of the lack of a chiral ligand.
[0022] Casey's group (Casey et al., "An efficient and
chemoselective iron catalyst for the hydrogenation of ketones," J.
Am. Chem. Soc. 129 (2007), pp. 5816-5817) reported that an achiral
complex of the type Fe(arene-OH)H(CO).sub.2 is a hydrogenation
catalyst but not an asymmetric hydrogenation catalyst for ketones
and imines at room temperature. It also catalyzes the hydrogenation
of acetophenone by transfer from isopropanol. The complex
[NMe.sub.4][Fe.sub.3H(CO).sub.11] catalyzes the complete conversion
of ketones to alcohols at 80-100.degree. C. within 1-24 h by using
alcohols as the reductant (Jothimony et al. "Mechanism for transfer
hydrogenation of ketones to alcohols catalyzed by hydridotriiron
undecacarbonylate anion under phase transfer conditions," 52 J.
Molec. Cat. (1989), pp. 301-304) but this is not an asymmetric
reduction. Bart et al. (Bart et al., "Preparation and molecular and
electronic structures of iron(0) dinitrogen and silane complexes
and their application to catalytic hydrogenation and
hydrosilation," J. Am. Chem. Soc. 126 (2004), pp. 13794-13795) have
reported achiral iron catalysts that hydrogenate olefins under mild
conditions.
[0023] Thus, there is a need for new catalysts for hydrogenation,
asymmetric hydrogenation, transfer hydrogenation, and asymmetric
transfer hydrogenation which do not require the use of PGMs.
SUMMARY OF THE INVENTION
[0024] In one aspect, there is a provided a hexa-coordinate iron
(II) complex comprising a compound of formula (I):
##STR00008##
wherein each R.sup.1 is independently selected from the group
consisting of aryl, heteroaryl, C.sub.1-C.sub.8 alkyl,
C.sub.2-C.sub.8 alkenyl, C.sub.1-C.sub.8 alkoxy, aryloxy, and
cycloalkyl, all of which may be optionally substituted; two geminal
R.sup.1 groups may combine to form a C.sub.2-C.sub.4 linear alkyl
diradical or C.sub.3-C.sub.8 branched alkyl diradical, each of
which may be optionally substituted, to form a ring together with
the phosphorus atom to which they are attached; or two R.sup.1
groups, each of which is located on a different phosphorus atom,
may combine to form a linker M, wherein M is selected from the
group consisting of C.sub.2-C.sub.4 linear alkyl diradical and
C.sub.3-C.sub.8 branched alkyl diradical, each of which may be
optionally substituted, or M may be a diradical ligand with a wide
bite angle;
[0025] A is selected from:
##STR00009##
[0026] wherein each R.sup.2 and R.sup.3 are independently selected
from the group consisting of H, substituted or unsubstituted
C.sub.1-C.sub.8 alkyl, substituted or unsubstituted C.sub.2-C.sub.8
alkenyl, substituted or unsubstituted aryl, and substituted or
unsubstituted cycloalkyl, and each n is an integer independently
selected from 1, 2, and 3;
[0027] each R.sup.4 is independently selected from the group
consisting of H, substituted or unsubstituted C.sub.1-C.sub.8
alkyl, substituted or unsubstituted C.sub.2-C.sub.8 alkenyl,
substituted or unsubstituted aryl, and substituted or unsubstituted
cycloalkyl;
[0028] each R.sup.5, R.sup.6, R.sup.7 and R.sup.8 is independently
selected from the group consisting of H, substituted or
unsubstituted C.sub.1-C.sub.8 alkyl, substituted or unsubstituted
C.sub.2-C.sub.8 alkenyl, substituted or unsubstituted aryl, and
substituted or unsubstituted cycloalkyl; R.sup.5 and R.sup.6,
together with the carbon atom to which they are attached, may
combine to form a substituted or unsubstituted cycloalkyl ring of
size from 5-8 carbons; R.sup.7 and R.sup.8, together with the
carbon atom to which they are attached, may combine to form a
substituted or unsubstituted cycloalkyl ring of size from 5-8
carbons; or R.sup.5, R.sup.6, R.sup.7 and R.sup.8, together with
the carbon atoms to which they are attached, may combine to form a
group selected from
##STR00010##
each of which may be optionally substituted with one or more
substituents selected from the group consisting of C.sub.1-C.sub.8
alkyl, C.sub.1-C.sub.8 alkoxy, and halogen atoms;
[0029] L.sup.1 and L.sup.2 are independently selected from the
group consisting of CO; hydride; pyridine and derivatives thereof;
imidazole and derivatives thereof; halide ion; NCR, CNR and
.sup.-OR, wherein R is independently selected from the group
consisting of aryl, heteroaryl, C.sub.1-C.sub.8 alkyl,
C.sub.2-C.sub.8 alkenyl and cycloalkyl, all of which may be
optionally substituted; R.sup.aR.sup.bR.sup.cN wherein R.sup.a,
R.sup.b, and R.sup.c are independently selected from the group
consisting of H and C.sub.1-C.sub.2 alkyl; and R.sup.c(CO)R.sup.d
wherein R.sup.c and R.sup.d are independently selected from the
group consisting of C.sub.1-C.sub.8 alkyl, aryl, and
heteroaryl;
[0030] m represents the charge of the compound of formula (I) and
is 0, +1, or +2; and when m is +1 or +2, the iron (II) complex
comprises at least one counter ion to counterbalance the charge of
the compound of formula (I);
[0031] with the proviso that when A is
##STR00011##
then at least one of L.sup.1 and L.sup.2 must be selected from the
group consisting of CO and CNR, wherein R is as defined above.
[0032] In another aspect, there is provided a process for the
preparation of a hexa-coordinate iron (II) complex of formula (I),
the process comprising reacting a phosphinaldehyde precursor of
formula (V):
##STR00012##
wherein
[0033] each R.sup.1 is independently selected from the group
consisting of aryl, heteroaryl, C.sub.1-C.sub.8 alkyl,
C.sub.2-C.sub.8 alkenyl, C.sub.1-C.sub.8 alkoxy, aryloxy, and
cycloalkyl, all of which may be optionally substituted; two geminal
R.sup.1 groups may combine to form a C.sub.2-C.sub.4 linear alkyl
diradical or C.sub.3-C.sub.8 branched alkyl diradical, each of
which may be optionally substituted, to form a ring together with
the phosphorus atom to which they are attached; or two R.sup.1
groups, each of which is located on a different phosphorus atom,
may combine to form a linker M, wherein M is selected from the
group consisting of C.sub.2-C.sub.4 linear alkyl diradical and
C.sub.3-C.sub.8 branched alkyl diradical, each of which may be
optionally substituted, or M may be a diradical ligand with a wide
bite angle;
[0034] A is
##STR00013##
[0035] wherein each R.sup.2 and R.sup.3 are independently selected
from the group consisting of H, substituted or unsubstituted
C.sub.1-C.sub.8 alkyl, substituted or unsubstituted C.sub.2-C.sub.8
alkenyl, substituted or unsubstituted aryl, and substituted or
unsubstituted cycloalkyl, and each n is an integer independently
selected from 1, 2, and 3;
[0036] each R.sup.4 is independently selected from the group
consisting of H, substituted or unsubstituted C.sub.1-C.sub.8
alkyl, substituted or unsubstituted C.sub.2-C.sub.8 alkenyl,
substituted or unsubstituted aryl, and substituted or unsubstituted
cycloalkyl;
[0037] with a diamine of formula (VI):
##STR00014##
wherein
[0038] each R.sup.5, R.sup.6, R.sup.7 and R.sup.8 is independently
selected from the group consisting of H, substituted or
unsubstituted C.sub.1-C.sub.8 alkyl, substituted or unsubstituted
C.sub.2-C.sub.8 alkenyl, substituted or unsubstituted aryl, and
substituted or unsubstituted cycloalkyl; R.sup.5 and R.sup.6,
together with the carbon atom to which they are attached, may
combine to form a substituted or unsubstituted cycloalkyl ring of
size from 5-8 carbons; R.sup.7 and R.sup.8, together with the
carbon atom to which they are attached, may combine to form a
substituted or unsubstituted cycloalkyl ring of size from 5-8
carbons; or R.sup.5, R.sup.6, R.sup.7 and R.sup.8, together with
the carbon atoms to which they are attached, may combine to form a
group selected from
##STR00015##
[0039] each of which may be optionally substituted with one or more
substituents selected from the group consisting of C.sub.1-C.sub.8
alkyl, C.sub.1-C.sub.8 alkoxy, and halogen atoms;
[0040] in the presence of:
[0041] an iron (II) salt;
[0042] a ligand selected from the group consisting of CH.sub.3CN;
pyridine and derivatives thereof; and imidazole and derivatives
thereof; and
[0043] a strong base;
[0044] to form the compound of formula (I)
##STR00016##
[0045] wherein A, R.sup.1-R.sup.8, and n are as defined above,
[0046] m is +2,
[0047] L.sup.1 and L.sup.2 are both CH.sub.3CN; pyridine or a
derivative thereof; or imidazole or a derivative thereof;
[0048] and adding at least one counter ion to counterbalance the
charge of the compound of formula (I).
[0049] In another aspect, there is provided, a process for
preparing an alcoholic compound wherein said process comprises a
step of preparing the alcoholic compound by reducing a ketone or
aldehyde with the reaction of hydrogen or a compound donating
hydrogen in the presence of a hexa-coordinate iron (II) complex of
formula (I), with the proviso that the ketone is not an
unsubstituted cycloalkanone.
[0050] In still another aspect, there is provided a process for
preparing an amine compound wherein said process comprises a step
of preparing the amine compound by reducing an imine with the
reaction of hydrogen or a compound donating hydrogen in the
presence of a hexa-coordinate iron (II) complex of formula (I).
[0051] In yet another aspect, there is provided a hydrogenation
catalyst comprising a hexa-coordinate iron(II) complex of formula
(I)
##STR00017##
[0052] wherein a trans coordination geometry is achieved at iron
through nitrogen and phosphorus donor bonds of a tetradentate
diimino-diphosphine templated ligand of the formula (II):
R.sup.1.sub.2P-A-C(R.sup.4).dbd.N--C*(R.sup.5R.sup.6)--C*(R.sup.7R.sup.8-
)--N.dbd.C(R.sup.4)-A-PR.sup.1.sub.2 (II)
and L.sup.1 and L.sup.2 are in an axial coordination above and
below the templated ligand, respectively,
[0053] wherein the tetradentate diimino-diphosphine templated
ligand is the reaction product of a phosphinaldehyde precursor of
formula (V)
##STR00018##
[0054] and a diamine precursor of formula (VI)
##STR00019##
Wherein
[0055] each R.sup.1 is independently selected from the group
consisting of aryl, heteroaryl, C.sub.1-C.sub.8 alkyl,
C.sub.2-C.sub.8 alkenyl, C.sub.1-C.sub.8 alkoxy, aryloxy, and
cycloalkyl, all of which may be optionally substituted; two geminal
R.sup.1 groups may combine to form a C.sub.2-C.sub.4 linear alkyl
diradical or C.sub.3-C.sub.8 branched alkyl diradical, each of
which may be optionally substituted, to form a ring together with
the phosphorus atom to which they are attached; or two R.sup.1
groups, each of which is located on a different phosphorus atom,
may combine to form a linker M, wherein M is selected from the
group consisting of C.sub.2-C.sub.4 linear alkyl diradical and
C.sub.3-C.sub.8 branched alkyl diradical, each of which may be
optionally substituted, or M may be a diradical ligand with a wide
bite angle;
A is selected from:
##STR00020##
[0056] wherein each R.sup.2 and R.sup.3 are independently selected
from the group consisting of H, substituted or unsubstituted
C.sub.1-C.sub.8 alkyl, substituted or unsubstituted C.sub.2-C.sub.8
alkenyl, substituted or unsubstituted aryl, and substituted or
unsubstituted cycloalkyl, and each n is an integer independently
selected from 1, 2, and 3;
[0057] each R.sup.4 is independently selected from the group
consisting of H, substituted or unsubstituted C.sub.1-C.sub.8
alkyl, substituted or unsubstituted C.sub.2-C.sub.8 alkenyl,
substituted or unsubstituted aryl, and substituted or unsubstituted
cycloalkyl;
[0058] each R.sup.5, R.sup.6, R.sup.7 and R.sup.8 is independently
selected from the group consisting of H, substituted or
unsubstituted C.sub.1-C.sub.8 alkyl, substituted or unsubstituted
C.sub.2-C.sub.8 alkenyl, substituted or unsubstituted aryl, and
substituted or unsubstituted cycloalkyl; R.sup.5 and R.sup.6,
together with the carbon atom to which they are attached, may
combine to form a substituted or unsubstituted cycloalkyl ring of
size from 5-8 carbons; R.sup.7 and R.sup.8, together with the
carbon atom to which they are attached, may combine to form a
substituted or unsubstituted cycloalkyl ring of size from 5-8
carbons; or R.sup.5, R.sup.6, R.sup.7 and R.sup.8, together with
the carbon atoms to which they are attached, may combine to form a
group selected from
##STR00021##
[0059] each of which may be optionally substituted with one or more
substituents selected from the group consisting of C.sub.1-C.sub.8
alkyl, C.sub.1-C.sub.8 alkoxy, and halogen atoms;
[0060] L.sup.1 and L.sup.2 are independently selected from the
group consisting of CO; hydride; pyridine and derivatives thereof;
imidazole and derivatives thereof; halide ion; NCR, CNR and
.sup.-OR, wherein R is independently selected from the group
consisting of aryl, heteroaryl, C.sub.1-C.sub.8 alkyl,
C.sub.2-C.sub.8 alkenyl and cycloalkyl, all of which may be
optionally substituted; R.sup.aR.sup.bR.sup.cN wherein R.sup.a,
R.sup.b, and R.sup.c are independently selected from the group
consisting of H and C.sub.1-C.sub.2 alkyl; and R.sup.c(CO)R.sup.d
wherein R.sup.c and R.sup.d are independently selected from the
group consisting of C.sub.1-C.sub.8 alkyl, aryl, and
heteroaryl;
[0061] m represents the charge of the compound of formula (I) and
is 0, +1, or +2; and when m is +1 or +2, the iron (II) complex
comprises at least one counter ion to counterbalance the charge of
the compound of formula (I);
[0062] with the proviso that when A is
##STR00022##
then at least one of L.sup.1 and L.sup.2 must be selected from the
group consisting of CO and CNR, wherein R is as defined above.
[0063] In still another aspect, there is provided a process for the
preparation of a hexa-coordinate iron (II) complex, the process
comprising reacting a phosphinaldehyde precursor of formula
(V):
##STR00023##
wherein
[0064] each R.sup.1 is independently selected from the group
consisting of aryl, heteroaryl, C.sub.1-C.sub.8 alkyl,
C.sub.2-C.sub.8 alkenyl, C.sub.1-C.sub.8 alkoxy, aryloxy, and
cycloalkyl, all of which may be optionally substituted; two geminal
R.sup.1 groups may combine to form a C.sub.2-C.sub.4 linear alkyl
diradical or C.sub.3-C.sub.8 branched alkyl diradical, each of
which may be optionally substituted, to form a ring together with
the phosphorus atom to which they are attached; or two R.sup.1
groups, each of which is located on a different phosphorus atom,
may combine to form a linker M, wherein M is selected from the
group consisting of C.sub.2-C.sub.4 linear alkyl diradical and
C.sub.3-C.sub.8 branched alkyl diradical, each of which may be
optionally substituted, or M may be a diradical ligand with a wide
bite angle;
A is
##STR00024##
[0066] wherein each R.sup.2 and R.sup.3 are independently selected
from the group consisting of H, substituted or unsubstituted
C.sub.1-C.sub.8 alkyl, substituted or unsubstituted C.sub.2-C.sub.8
alkenyl, substituted or unsubstituted aryl, and substituted or
unsubstituted cycloalkyl, and each n is an integer independently
selected from 1, 2, and 3;
[0067] each R.sup.4 is independently selected from the group
consisting of H, substituted or unsubstituted C.sub.1-C.sub.8
alkyl, substituted or unsubstituted C.sub.2-C.sub.8 alkenyl,
substituted or unsubstituted aryl, and substituted or unsubstituted
cycloalkyl;
with a diamine of formula (VI):
##STR00025##
wherein
[0068] each R.sup.5, R.sup.6, R.sup.7 and R.sup.8 is independently
selected from the group consisting of H, substituted or
unsubstituted C.sub.1-C.sub.8 alkyl, substituted or unsubstituted
C.sub.2-C.sub.8 alkenyl, substituted or unsubstituted aryl, and
substituted or unsubstituted cycloalkyl; R.sup.5 and R.sup.6,
together with the carbon atom to which they are attached, may
combine to form a substituted or unsubstituted cycloalkyl ring of
size from 5-8 carbons; R.sup.7 and R.sup.8, together with the
carbon atom to which they are attached, may combine to form a
substituted or unsubstituted cycloalkyl ring of size from 5-8
carbons; or R.sup.5, R.sup.6, R.sup.7 and R.sup.8, together with
the carbon atoms to which they are attached, may combine to form a
group selected from
##STR00026##
each of which may be optionally substituted with one or more
substituents selected from the group consisting of C.sub.1-C.sub.8
alkyl, C.sub.1-C.sub.8 alkoxy, and halogen atoms;
[0069] in the presence of:
[0070] an iron (II) salt;
[0071] a ligand selected from the group consisting of CH.sub.3CN;
pyridine and derivatives thereof; and imidazole and derivatives
thereof; and
[0072] a strong base;
[0073] and further reacting the reaction product of the foregoing
steps with CO to produce a compound of formula (VIIIa):
##STR00027##
[0074] wherein A, R.sup.1-R.sup.8, and n are as defined above,
L.sub.1 is CO, L.sup.2' is Br, and m is +1;
[0075] and adding a counter ion to counterbalance the charge of the
compound of formula (VIIIa).
[0076] A process for preparing a phosphonium dimer of formula
(XIII) is provided:
##STR00028##
[0077] wherein R.sup.1 is selected from the group consisting of
C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 substituted alkyl,
cycloalkyl, and substituted cycloalkyl, and X is selected from the
group consisting of Br and I, the process comprising:
[0078] reacting a compound of formula (XI):
[0079] HPR.sup.1.sub.2 (XI)
[0080] wherein R.sup.1 is as defined above;
[0081] with a compound of formula (XII):
##STR00029##
[0082] wherein X is as defined above, and R.sup.e is
C.sub.1-C.sub.8 alkyl, or the two Re can combine to form a
C.sub.2-C.sub.3 linear alkyl diradical;
[0083] and heating the reaction product in the presence of water to
form the phosphonium dimer of formula (XIII).
DETAILED DESCRIPTION
[0084] Iron (II) complexes with PNNP donor ligands as catalytic
materials for the hydrogenation, asymmetric hydrogenation, transfer
hydrogenation, and/or asymmetric transfer hydrogenation of ketones
and imines are disclosed.
[0085] The asymmetric hydrogenation technology described herein
that provides a specified enantiomer enables a more economical,
safer, efficient, and greener chemical way to generate compounds
that are significantly enriched in the required enantiomer.
[0086] As noted above, conventional asymmetric hydrogenation
catalysts utilize platinum group metals (PGM) ruthenium, osmium,
rhodium, iridium, palladium or platinum (De Vries et al., "Handbook
of Homogeneous Hydrogenation" Wiley-VCH, volumes 1-3, 2007). PGM
are expensive and thereby add to the cost of the final product. In
addition, they are in limited supply and not readily available. By
contrast, iron is inexpensive, abundant and biocompatible. An
unexpected feature of the disclosed catalysts is the high activity
that they display in the activation of hydrogen gas toward the
hydrogenation of ketones and in the activation of hydrogen-donor
molecules such as isopropanol toward the transfer hydrogenation of
ketones and imines.
[0087] In one embodiment, there is provided a hexa-coordinate iron
(II) complex comprising a compound of formula (I):
##STR00030##
Wherein
[0088] each R.sup.1 is independently selected from the group
consisting of aryl, heteroaryl, C.sub.1-C.sub.8 alkyl,
C.sub.2-C.sub.8 alkenyl, C.sub.1-C.sub.8 alkoxy, aryloxy, and
cycloalkyl, all of which may be optionally substituted; two geminal
R.sup.1 groups may combine to form a C.sub.2-C.sub.4 linear alkyl
diradical or C.sub.3-C.sub.8 branched alkyl diradical, each of
which may be optionally substituted, to form a ring together with
the phosphorus atom to which they are attached; or two R.sup.1
groups, each of which is located on a different phosphorus atom,
may combine to form a linker M, wherein M is selected from the
group consisting of C.sub.2-C.sub.4 linear alkyl diradical and
C.sub.3-C.sub.8 branched alkyl diradical, each of which may be
optionally substituted, or M may be a diradical ligand with a wide
bite angle;
[0089] A is selected from:
##STR00031##
[0090] wherein each R.sup.2 and R.sup.3 are independently selected
from the group consisting of H, substituted or unsubstituted
C.sub.1-C.sub.8 alkyl, substituted or unsubstituted C.sub.2-C.sub.8
alkenyl, substituted or unsubstituted aryl, and substituted or
unsubstituted cycloalkyl, and each n is an integer independently
selected from 1, 2, and 3;
[0091] each R.sup.4 is independently selected from the group
consisting of H, substituted or unsubstituted C.sub.1-C.sub.8
alkyl, substituted or unsubstituted C.sub.2-C.sub.8 alkenyl,
substituted or unsubstituted aryl, and substituted or unsubstituted
cycloalkyl;
[0092] each R.sup.5, R.sup.6, R.sup.7 and R.sup.8 is independently
selected from the group consisting of H, substituted or
unsubstituted C.sub.1-C.sub.8 alkyl, substituted or unsubstituted
C.sub.2-C.sub.8 alkenyl, substituted or unsubstituted aryl, and
substituted or unsubstituted cycloalkyl; R.sup.5 and R.sup.6,
together with the carbon atom to which they are attached, may
combine to form a substituted or unsubstituted cycloalkyl ring of
size from 5-8 carbons; R.sup.7 and R.sup.8, together with the
carbon atom to which they are attached, may combine to form a
substituted or unsubstituted cycloalkyl ring of size from 5-8
carbons; or R.sup.5, R.sup.6, R.sup.7 and R.sup.8, together with
the carbon atoms to which they are attached, may combine to form a
group selected from
##STR00032##
each of which may be optionally substituted with one or more
substituents selected from the group consisting of C.sub.1-C.sub.8
alkyl, C.sub.1-C.sub.8 alkoxy, and halogen atoms;
[0093] L.sup.1 and L.sup.2 are independently selected from the
group consisting of CO; hydride; pyridine and derivatives thereof;
imidazole and derivatives thereof; halide ion; NCR, CNR and
.sup.-OR, wherein R is independently selected from the group
consisting of aryl, heteroaryl, C.sub.1-C.sub.8 alkyl,
C.sub.2-C.sub.8 alkenyl and cycloalkyl, all of which may be
optionally substituted; R.sup.aR.sup.bR.sup.cN wherein R.sup.a,
R.sup.b, and R.sup.c are independently selected from the group
consisting of H and C.sub.1-C.sub.2 alkyl; and R.sup.c(CO)R.sup.d
wherein R.sup.c and R.sup.d are independently selected from the
group consisting of C.sub.1-C.sub.8 alkyl, aryl, and
heteroaryl;
[0094] m represents the charge of the compound of formula (I) and
is 0, +1, or +2; and when m is +1 or +2, the iron (II) complex
comprises at least one counter ion to counterbalance the charge of
the compound of formula (I);
[0095] with the proviso that when A is
##STR00033##
then at least one of L.sup.1 and L.sup.2 must be selected from the
group consisting of CO and CNR, wherein R is as defined above.
[0096] In another embodiment, a trans coordination geometry is
achieved at iron through nitrogen and phosphorus donor bonds of a
tetradentate diimino-diphosphine templated ligand of the formula
(II):
R.sup.1.sub.2P-A-C(R.sup.4).dbd.N--C*(R.sup.5R.sup.6)--C*(R.sup.7R.sup.8-
)--N.dbd.C(R.sup.4)-A-PR.sup.1.sub.2 (II)
[0097] and L.sup.1 and L.sup.2 are in an axial coordination above
and below the templated ligand, respectively.
[0098] In one embodiment, the at least one counter ion is selected
from BF.sub.4.sup.-; PF.sub.6.sup.-; SbF.sub.6.sup.-;
ClO.sub.4.sup.-; CH.sub.3SO.sub.3.sup.-; CF.sub.3SO.sub.3.sup.-;
C.sub.6H.sub.5SO.sub.3.sup.-;
p-CH.sub.3C.sub.6H.sub.4SO.sub.3.sup.-; FeCl.sub.4.sup.2-;
FeBr.sub.4.sup.2-; B(R*).sub.4.sup.-, wherein R* is selected from
phenyl, C.sub.6H.sub.3(CF.sub.3).sub.2 and C.sub.6F.sub.5; halides;
pseudohalides; C.sub.1-C.sub.8 alkoxides; and aryloxides. In
another embodiment, the at least one counter ion is BF.sub.4.sup.-.
In another embodiment, the at least one counter ion is
BPh.sub.4.sup.-.
[0099] In another embodiment, R.sup.1 is substituted or
unsubstituted aryl. In other embodiments, R.sup.1 is phenyl.
[0100] In another embodiment, A is
##STR00034##
In another embodiment, R.sup.4 is H. In yet another embodiment,
R.sup.5, R.sup.6, R.sup.2 and R.sup.8, together with the carbon
atoms to which they are attached, combine to form
##STR00035##
In certain embodiments, the chiral carbon atoms denoted by
asterisks both have an R configuration. In other embodiments, the
chiral carbon atoms denoted by asterisks both have an S
configuration.
[0101] In still another embodiment, A is
##STR00036##
In another embodiment, R.sup.4 is H. In another embodiment,
R.sup.2.dbd.R.sup.3.dbd.H. In yet another embodiment, n=1.
[0102] In another embodiment, R.sup.5.dbd.R.sup.8=substituted or
unsubstituted aryl and R.sup.6.dbd.R.sup.2.dbd.H. In another
embodiment, R.sup.5.dbd.R.sup.8=phenyl. In still another
embodiment, the chiral carbon atoms bearing the substituents
R.sup.5 and R.sup.6, and R.sup.2 and R.sup.8, respectively, both
have an R configuration. In another embodiment, these chiral carbon
atoms have an S configuration.
[0103] In another embodiment,
R.sup.4.dbd.R.sup.5.dbd.R.sup.6.dbd.R.sup.7.dbd.R.sup.8.dbd.H.
[0104] In another embodiment, L.sup.1 and L.sup.2 are CH.sub.3CN.
In still another embodiment, L.sup.1 is CH.sub.3CN and L.sup.2 is
selected from CO or CNR, wherein R is C.sub.1-C.sub.8 alkyl. In
another embodiment, L.sup.2 is CNtBu.
[0105] In another embodiment, the hexa-coordinate iron (II) complex
comprises a compound having the structure:
##STR00037##
[0106] In another embodiment, the chiral carbon atoms denoted by
asterisks both have an R configuration. In another embodiment, the
chiral carbon atoms denoted by asterisks both have an S
configuration.
[0107] As noted above, the A symbol represents the bridging group
--(CR.sup.2R.sup.3).sub.n. In one embodiment, n is 1, R.sup.3 is H
and R.sup.2 is H. In other embodiments, R.sup.3 is H and R.sup.2
may be selected from aryl or C.sub.1-C.sub.8 alkyl, each of which
may be optionally substituted. When R.sup.2.noteq.R.sup.3, the
carbon bearing these substituents is chiral and may be
enantiopure.
[0108] In other embodiments, n may be 2, and A is then
--CR.sup.2R.sup.3CR.sup.2R.sup.3--. In further embodiments, n may
be 3 and A is then
--CR.sup.2R.sup.3CR.sup.2R.sup.3CR.sup.2R.sup.3--. In one
embodiment, all R.sup.3 may be H. In another embodiment, each
R.sup.3 may be different. Likewise, the R.sup.2 groups may be the
same or different.
[0109] In another embodiment, R.sup.5, R.sup.6, R.sup.7 and R.sup.8
can be selected to produce enantiopure structures. For instance,
the cyclohexyldiyl structure noted above may be present as the
(R,R) or (S,S) enantiopure isomer (having regard to the chiral
carbon atoms denoted by asterisks).
[0110] The various chemical terms used herein are to be given their
ordinary meaning as would be understood by persons skilled in the
art, unless provided otherwise.
[0111] The following chemical terms presently described apply to
all compounds and processes disclosed herein, unless provided
otherwise.
[0112] A "templated ligand" is a molecule that forms from precursor
parts that coordinate to a metal ion at geometrically defined
positions such as octahedral or square planar, for example, and
bond together. The metal ion acts as template for the formation of
this ligand. Given the same reaction conditions, but in the absence
of the metal template, the precursor parts usually either do not
react, or do react but form a mixture of products, none of which
have the structure of the templated ligand.
[0113] The compounds of formula (I) disclosed herein are referred
to herein as "catalysts". However, it will be understood by a
person of skill in the art that further study may reveal that these
compounds are in theory "pre-catalysts" and are converted to an
active form during the hydrogenation reactions.
[0114] The term "C.sub.1-C.sub.8 alkyl" as used herein either alone
or in combination with another substituent means acyclic, linear or
branched chain alkyl substituent containing from one to eight
carbons and includes for example, methyl, ethyl, 1-methylethyl,
1-methylpropyl, 2-methylpropyl, butyl and the like.
[0115] The term "C.sub.2-C.sub.8 alkenyl", as used herein, either
alone or in combination with another radical, is intended to mean
an unsaturated, acyclic linear chain radical containing from two to
eight carbon atoms, at least two of which are bonded to each other
by a double bond. Examples of such radicals include, but are not
limited to, ethenyl (vinyl), 1-propenyl, 2-propenyl, and 1-butenyl.
The alkenyl groups may contain any number of double bonds.
[0116] The term "aryl" as used herein, either alone or in
combination with another substituent, means an aromatic monocyclic
system containing 6 carbon atoms or an aromatic bicyclic system
containing 10 carbon atoms. The rings may have substituents
including alkyl groups or alkoxy groups. For instance, a phenyl
ring may have substituents such as in the 3 and 5 positions, or 2
and 6 positions, or in the 4 position. The term "aryl" includes but
is not limited to a phenyl, tolyl (substituted aryl) or naphthyl
group.
[0117] The term "heteroaryl" as used herein, either alone or in
combination with another substituent means a 5, 6, 7, or 8-membered
unsaturated heterocycle containing one oxygen or sulfur or from one
to 4 nitrogen heteroatoms and which form an aromatic system. For
example, the term "heteroaryl" includes a furyl, pyridyl, or
quinolinyl group.
[0118] The term "cycloalkyl" as used herein, either alone or in
combination with another substituent, means a cycloalkyl
substituent that includes for example, but is not limited to,
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and
cycloheptyl
[0119] The term "alkoxy" as used herein, either alone or in
combination with another radical, means the radical
--O--(C.sub.1-n) alkyl wherein the alkyl group contains 1 or more
carbon atoms, and includes for example methoxy, ethoxy, propoxy,
1-methylethoxy, butoxy, cyclohexyloxy and 1,1-dimethylethoxy.
"Alkoxide" refers to the radial .sup.-O--(C.sub.1-n) alkyl bearing
a negative charge.
[0120] The term "aryloxy" as used herein, either alone or in
combination with another radical, means the radical --O-aryl
wherein aryl is defined as above, such as phenyl.
[0121] The term "aromatic diradical" includes groups such as benzo,
as well as naphthyl diradical, binaphthyl diradical, and
bisoxynaphthyl diradical as derived from BINOL. The term "branched
alkyl diradical" includes groups such as 1,4-dimethylbutanediyl. In
one aspect, the branched alkyl diradical may have between 3 and 8
carbon atoms. Such diradicals may be enantiopure. The term "linear
alkyl diradical" includes C.sub.2-C.sub.4 linear alkyl diradicals
such as 1,2-ethylene, 1,3-propylene, and 1,4-butylene.
[0122] The term "diradical that spans a wide bite angle" refers to
aromatic diradicals such as naphthyl diradicals or tricyclic groups
such as the 4,5-diradical of 9,9-dimethylxanthene and other groups
described in the article by Kramer et al. Acc. Chem. Res. 2001, 34,
895-904, the contents of which are hereby incorporated herein by
reference.
[0123] The term "halogen" refers to F, Cl, Br, and I. The term
"halide ion" refers to a halogen atom bearing a negative
charge.
[0124] The term "pseudohalide" refers to anions that behave
chemically like halides. These include OCN.sup.-, SCN.sup.-,
CN.sup.- and NNN.sup.-.
[0125] As noted above, certain of the R.sup.1-R.sup.8 groups may be
optionally substituted. Those of skill in the art will understand
that a suitable substituent includes, for example, methyl
substituents on aryl groups to generate tolyl or xylyl groups and
the like. Suitable substituents for aryl, heteroaryl, and
cycloalkyl functionalities include C.sub.1-C.sub.8 alkyl, branched
or linear, alkoxy or halogen atoms. Suitable substituents for each
"R" group mentioned in the claims include methyl, isopropyl,
tertiary-butyl and phenyl.
[0126] It is to be understood that a suitable substituent is a
substituent that does not interfere with the formation of the
desired product by the claimed processes and methods disclosed
herein. It is understood, of course, that the R groups defined
herein (R.sup.1-R.sup.8, etc.) will not contain any substitution or
substitution patterns which are sterically impractical and/or
synthetically non-feasible.
[0127] As noted above, the L.sup.1, L.sup.2 symbols, taken
separately, represent simultaneously or independently CO; hydride;
pyridine and derivatives thereof, including but not limited to
4-picoline or 3-picoline; imidazole and derivatives thereof,
including but not limited to N-methyl imidazole; halide ion; NCR,
CNR and .sup.-OR, wherein R is independently selected from aryl,
heteroaryl, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl and
cycloalkyl, all of which may be optionally substituted;
R.sup.aR.sup.bR.sup.cN wherein R.sup.a, R.sup.b, and R.sup.c are
independently selected from H and C.sub.1-C.sub.2 alkyl; and
R.sup.c(CO)R.sup.d wherein R.sup.c and R.sup.d are independently
selected from C.sub.1-C.sub.8 alkyl, aryl, and heteroaryl.
[0128] The charge on the complex (m) depends on the nature of the
P--N--N--P ligand and the ligands L.sup.1 and L.sup.2 and can vary
from 0 to +2. The charge m+ on the metal is 2+ when the ligands
L.sup.1 and L.sup.2 are neutral, 1+ when one of L.sup.1 or L.sup.2
is anionic, 0 when both L.sup.1 and L.sup.2 are anionic.
[0129] To counterbalance this charge in the metal complex salt, at
least one counter ion is present. The term "counter ion" refers to
an ion that is associated with the compounds of formula (I)
disclosed herein in order to counterbalance the charge of the
compound of formula (I) in the iron (II) complex. Such counter ions
may include for example anions selected from the group comprising
BF.sub.4.sup.-; PF.sub.6.sup.-; SbF.sub.6.sup.-; ClO.sub.4.sup.-;
CH.sub.3SO.sub.3.sup.-; CF.sub.3SO.sub.3.sup.-;
C.sub.6H.sub.5SO.sub.3.sup.-;
p-CH.sub.3C.sub.6H.sub.4SO.sub.3.sup.-; FeCl.sub.4.sup.2-;
FeBr.sub.4.sup.2-; B(R*).sub.4.sup.-, wherein R* is selected from
phenyl, C.sub.6H.sub.3(CF.sub.3).sub.2 and C.sub.6F.sub.5; halides;
pseudohalides; alkoxides such as C.sub.1-C.sub.8 alkoxides and
aryloxides such as phenoxide.
[0130] Compounds donating hydrogen include lower alcohols such as
methanol, ethanol, propanol, 2-propanol or butanol, and formic
acid.
[0131] In particular the enantiopure complex (i) is useful for
hydrogenation of ketones and imines, asymmetric hydrogenation of
prochiral ketones and imines, and is useful as a precursor for the
complex (ii). Complex (i) has been crystallized as the
BF.sub.4.sup.- and the BPh.sub.4.sup.- salt (see Example 1) and
characterized by elemental analyses, NMR, IR, MS and single crystal
X-ray diffraction. The (S,S)-enantiomer of complex (i) has also
been prepared.
##STR00038##
[0132] The performance of the catalyst (i) was tested on 10
different aromatic ketones according to the reaction
##STR00039##
where S:C:B refers to the substrate to catalyst to base ratio. The
procedure of the catalytic runs was performed as follows:
(.sup.a)
TABLE-US-00001 TABLE 1 The hydrogenation of ketones catalyzed by
(i) and base KO.sup.tBu (S/C/B = 200/1/15) in 9 mL isopropanol at
35.degree. C. under 10 atm H.sub.2. Time Conv. e.e. (S) Entry
Substrate (min) (%) (%) 1 Ph--CO--Me 30 40-90 81 2 Ph--CO--Et 25
35-80 92 3 Ph--CO--iPr 30 5 99 4 Ph--CH.sub.2--CH.sub.2--CO--Me
25/50 45-90/56-98 1 5 (4'-ClC.sub.6H.sub.4)--CO--Me 20 55-91 91 6
(4'-MeOC.sub.6H.sub.4)--CO--Me 20 60-94 88 7
(3'-ClC.sub.6H.sub.4)--CO--Me 180 10-45 82 8
(3'-BrC.sub.6H.sub.4)--CO--Me 30 5-30 86 9
(2'-ClC.sub.6H.sub.4)--CO--Me 30 35-58 75 10 1-Acetonaphthone 360
55-96 95
[0133] In the N.sub.2 glovebox, the iron complex (10 mg, 0.007
mmol), KO.sup.tBu (12.3 mg, 0.107 mmol) and the substrate were
separately dissolved in the 3 mL of 2-propanol, each. The resulting
solutions in the order substrate, then base, and then catalyst were
injected into a 50 cm.sup.3 Parr hydrogenator reactor at the
desired pressure and temperature, maintained by use of a Fischer
Scientific Isotemp 1016D water bath under a hydrogen
atmosphere.
[0134] Complex (ii), shown below, has been crystallized as the
BPh.sub.4.sup.- salt (see Example 2) and characterized by elemental
analyses, NMR, IR, MS and single crystal X-ray diffraction. The
(S,S)-enantiomer has also been prepared and completely
characterized. Enantiopure complex (ii) is useful for the transfer
hydrogenation of ketones and imines and asymmetric transfer
hydrogenation of prochiral ketones and imines.
##STR00040##
TABLE-US-00002 TABLE 2 The transfer hydrogenation of ketones to the
(S) alcohols catalyzed by (ii) and base KO.sup.tBu (S/C/B =
1600/1/8 unless specified) isopropanol at 22.degree. C..sup.(a)
Entry Substrate Time (min) Conv. % ee % 1 Ph--CO--Me.sup.(b) 30 90
83 2 Ph--CO--Et.sup.(c) 50 84 93 3
(4-ClC.sub.6H.sub.4)--CO--Me.sup.(c) 50 93 70 4
(4-MeO--C.sub.6H.sub.4)--CO--Me.sup.(c) 50 78 81 5
1-acetonaphthone.sup.(d) 50 93 95 6 Ph--CO-.sup.iPr.sup.(c) 50 89
91 .sup.(a)In the N.sub.2 glovebox, the iron complex (ii) (2.0 mg,
0.0014 mmol), KOtBu (1.3 mg, 0.0114 mmol) and ketone (2.2 mmol)
were separately dissolved in the 5 mL of 2-propanol, each. The
resulting solutions were added to a vial charged with a stirring
bar in the order: substrate, catalyst followed by base. The samples
of the reaction mixture were analyzed by GC. .sup.(b)in 15 mL
isopropanol with S/C/B 2000/1/8. .sup.(c)in 12 mL isopropanol.
.sup.(d)in 14 mL isopropanol.
[0135] The enantiopure complex
trans-[Fe(NCMe)(CO)(9)](BF.sub.4).sub.2 (iii), wherein 9 is as
defined above:
##STR00041##
has also been prepared. This complex is inactive for catalytic
hydrogenation directly from H.sub.2 gas but is useful for the
asymmetric transfer hydrogenation of prochiral ketones and is
useful for the transfer hydrogenation of ketones and imines.
Complex (iii) has been crystallized as the BF.sub.4.sup.- (see
Example 4) and the BPh.sub.4.sup.- salt and characterized by
elemental analyses, NMR, IR, MS and single crystal X-ray
diffraction. The (S,S)-enantiomer of complex (iii) has also been
prepared and characterized. The enantiopure complex
trans-[Fe(NCMe)(CN.sup.tBu)(9)](BF.sub.4).sub.2 (iv) has also been
prepared and characterized (see Example 5).
##STR00042##
TABLE-US-00003 TABLE 3 Transfer hydrogenation of ketones and imines
from 2-propanol catalyzed by (iii) and KOtBu (S/C/B = 200/1/8) at
22.degree. C..sup.[a] Time Conv. e.e. TOF.sup.[e] Entry Substrate
(h) (%) (%) (h.sup.-1) 1.sup.[b] Ph--CO--Me 0.4 95 29 (S) 907
2.sup.[c] Ph--CO--Me 0.7 33 39 (S) 93 3 Ph--CO--Me 0.4 95 33 (S)
454 4 (2'-Cl--C.sub.6H.sub.4)--CO--Me 0.2 >99 18 (S) 995 5
(3'-Cl--C.sub.6H.sub.4)--CO--Me 0.4 99 24 (S) 495 6
(4'-Cl--C.sub.6H.sub.4)--CO--Me 0.2 94 26 (S) 938 7
(4'-Br--C.sub.6H.sub.4)--CO--Me 0.2 93 33 (S) 930 8
(4'-Me--C.sub.6H.sub.4)--CO--Me 0.6 86 33 (S) 279 9
(4'-OMe--C.sub.6H.sub.4)--CO--Me 0.5 69 23 (S) 260 10 Ph--CO--Et
3.6 95 61 (S) 26 11 C.sub.10H.sub.7--CO--Me.sup.[d] 0.3 94 25 (S)
564 12 Ph--CO--Ph 0.4 94 -- 470 13 Ph--(CH.sub.2).sub.2--CO--Me 0.6
100 29 (S) 315 14 Ph--CHO 2.4 94 -- 77 15 Ph--CH.dbd.N--Ph 17 100
-- 12 16 Ph--CMe.dbd.N--Ph 17 <5 -- -- 17 Cyclohexanone 17 0 --
-- .sup.[a]In an Ar or N.sub.2 glovebox at 22.degree. C., the iron
complex (5 mg, 0.005 mmol, [Cat] = 1.04 mM)), KOtBu (5 mg, 0.045
mmol) and substrate (200 equiv) were stirred in 5 mL of 2-propanol.
The conversion and enantiomeric excess of the products were
determined by NMR spectroscopy and GC. .sup.[b]S:C:B = 400:1:8,
[Cat] = 0.1 mM, 10 mL iPrOH. .sup.[c]S:C:B = 200:1:2, [Cat] = 0.1
mM, 5 mL iPrOH. .sup.[d]C.sub.10H.sub.7--CO--Me = 2-acetonaphthone.
.sup.[e]TOF = turn over frequencies.
[0136] .sup.[a]In an Ar or N.sub.2 glovebox at 22.degree. C., the
iron complex (5 mg, 0.005 mmol, [Cat]=1.04 mM), KOtBu (5 mg, 0.045
mmol) and the substrate (200 equiv) were stirred in 5 mL of
2-propanol. The conversion and enantiomeric excess of the products
were determined by NMR spectroscopy and GC. .sup.[b]S:C:B=400:1:8,
[Cat]=0.1 mM, 10 mL iPrOH. .sup.[c]S:C:B=200:1:2, [Cat]=0.1 mM, 5
mL iPrOH. .sup.[d]C.sub.10H.sub.7--CO--Me=2-acetonaphthone.
.sup.[e]TOF=turn over frequencies.
[0137] As can be seen from Table 3, the electronic properties of
the substituents on the phenyl ring of the ketone changed the
reduction rate but had less effect on the enantioselectivity
(18-33%). An acetophenone substituted in the para position by an
electron releasing group, such as 4'-methyl and 4'-methoxy, is
reduced more slowly than acetophenone (entries 3, 8 and 9). The
chloro substituted acetophenones are all reduced faster, especially
for the ortho position (entries 3-7). This trend is opposite to the
generally observed trend for Noyori's transfer hydrogenation
catalysts in which an ortho-Cl substitution decreases the rate of
the reduction (S. Hashiguchi, A. Fujii, J. Takehara, T. Ikariya, R.
Noyori, J. Am. Chem. Soc. 1995, 117, 7562). The catalyst (iii) with
KOtBu is also efficient for the transfer hydrogenation of
propiophenone, 2-acetonaphthone, benzophenone, benzylacetone,
benzaldehyde and N-benzylideneaniline (entries 11-15). The
hydrogenation of propiophenone gave 1-phenylpropanol in 61% e.e (S)
(entry 10). The more difficult ketimine
N-phenyl-(1-phenylethylidene)amine (Ph-CMe=N-Ph) was only partially
reduced (<5%) after 18 h under the same conditions (entry 16),
while cyclohexanone was not hydrogenated (entry 17). Transfer
hydrogenation of unsaturated ketones was complicated by some
reduction of the C.dbd.C double bond (Scheme 2).
##STR00043##
[0138] Complex (iv) is useful for the asymmetric transfer
hydrogenation of ketones. Complex (iv) was used in the transfer
hydrogenation of acetophenone, using the same reaction conditions
as noted for complex (iii) (see .sup.[a] in Table 3 above). After
2.6 hours the conversion was 34% and the e.e. was 76% (S).
[0139] The mechanism of the catalysis is uncertain. The
tetradentate ligand complex may be hydrogenated in the reaction
medium to produce the amine intermediate
[FeH(CO){(R,R)-cyP.sub.2(NH).sub.2}].sup.+; however, such a hydride
has not yet been synthesized or observed in the catalytic solution.
Such a complex might be expected to transfer a hydride from iron
and a proton from nitrogen to polar bonds in an outer sphere
hydrogenation, the mechanism postulated for the related complexes
[RuH.sub.2{(S,S)-cyP.sub.2(NH).sub.2}][15] and
[RuH.sub.2{PPh.sub.2(o-C.sub.6H.sub.4)CH.sub.2NHCMe.sub.2CMe.sub.2NHCH.su-
b.2(o-C.sub.6H.sub.4)PPh.sub.2}] (T. Li, R. Churlaud, A. J. Lough,
K. Abdur-Rashid, R. H. Morris, Organometallics 2004, 23, 6239).
Since there is poor chemoselectivity for the reduction of the
C.dbd.O bond versus the C.dbd.C during the hydrogenation of
trans-4-phenyl-3-buten-2-one, another mechanism might be
involved.
[0140] During the transfer hydrogenation of acetophenone catalyzed
by (iii) (entry 3, Table 3), the .sup.31P{1H} NMR shows an AB
pattern at 56 and 74 ppm (d, .sup.2J.sub.P-P=28 Hz) due to an, as
yet, unidentified intermediate. There is also a singlet for the
free ligand 9 (R,R)-cyP.sub.2N.sub.2, and some other minor,
unassigned peaks at 29 and -12.3 ppm. For the reaction catalyzed by
(iv), the AB pattern for the intermediate is observed at 54 and 58
ppm (d, .sup.2J.sub.P-P=31 Hz). This intermediate decomposes upon
attempt to isolate it from the catalytic mixture. Without being
bound by theory, it is thought that it might be a complex such as
[Fe(CO)(X){(R,R)-cyP.sub.2N.sub.2}](BF.sub.4), X=alkoxide or
hydride, but further study is required.
[0141] The observation of free PNNP ligand in the catalytic
solution may suggest the formation of colloidal iron; however,
there is evidence that the active catalyst is homogeneous instead
of heterogeneous in that the reaction solutions are clear. The e.e.
of the product alcohols are reproducible. There is no poisoning of
catalysis by mercury when it is added during the reaction (C. A.
Jaska, I. Manners, J. Am. Chem. Soc. 2004, 126, 9776).
[0142] As it follows from Table 2, TOF (turn over frequencies), TON
(turn over numbers) and enantioselectivity of the catalyst (ii) are
much higher compared to the catalysts (iii) and (iv). At a certain
moment of the reaction when equilibrium between product and a
substrate is established, catalytic racemization of the product
starts taking place. It is hard to propose a reliable mechanistic
explanation for such behavior of the catalyst at this point of
investigation, but the conditions of the reduction can be
optimized, so the product can be obtained in high yields and
enantiopurity. When a smaller amount of the base is used the rate
of the reaction is lower and thus the time at which racemization is
taking place can be defined. If the reaction is quenched by simple
exposure to air at this point of the process, high
enantioselectivity and yields of the reaction can be achieved.
Those conditions have a disadvantage: the overall rate of the
reaction and TOF are reduced. In order to reach high
enantioselectivity and conversion of the process the substrate
concentration was increased. That increased the time of the
reaction enough to determine when the equilibrium is established
without reduction of the TOF and product was obtained in good ee,
conversion and excellent TOF and TON.
[0143] Yellow solutions of complex (iii) are stable to oxidation in
air for at least one day. The .sup.1H NMR spectrum of (iii) showed
the presence of a singlet for the imine protons at 9.11 ppm while
the .sup.13C{1H} NMR spectrum displayed a pseudo-triplet for the
carbonyl carbon. The .sup.1H NMR spectrum of complex (iv) has two
distinct resonances for the imines protons. The .sup.31P{.sup.1H}
NMR spectra consist of AB patterns at ca. 51 and 48 ppm
(.sup.2J.sub.P-P.sup..about.40 Hz) for (iii) and ca. 58 and 48 ppm
(.sup.2J.sub.P-P=51 Hz) for (iv). The IR spectra of (iii) and (iv)
proved valuable. The carbonyl ligand of (iii) absorbs at 2000
cm.sup.-1. Complex (iv) has absorptions at 2151 and 2173 cm.sup.-1
for the tBuNC and MeCN ligands.
[0144] Similarly, the enantiopure complex (v) is useful for
asymmetric transfer hydrogenation of prochiral ketones and imines
and is useful for the transfer hydrogenation of ketones and imines.
Complex (v) has been crystallized as the BF.sub.4.sup.- salt (see
Example 7) and characterized by elemental analyses, NMR, IR, MS.
The (S,S)-enantiomer of complex (v) has also been prepared and
characterized including a single crystal X-ray diffraction
study.
##STR00044##
TABLE-US-00004 TABLE 4 Transfer hydrogenation of ketones from
2-propanol (6 mL) catalyzed by (v) and KOtBu (S/C/B = 600/1/8
unless specified) at 24.degree. C. under N.sub.2..sup.(a) Time
Conv. e.e. Entry Substrate (min) (%) (%) 1 Ph--CO--Me 30 71 63 (S)
2 Ph--CO--Et 30 75 70 (S) 3 Ph--CO--.sup.iPr 30 58 94 (S) 4
Ph--CO--.sup.tBu.sup.b 15 93 96 (S) 5
(2'-Cl--C.sub.6H.sub.4)--CO--Me 30 93 29 (S) 6
(3'-Cl--C.sub.6H.sub.4)--CO--Me 30 68 45 (S) 7
(4'-Cl--C.sub.6H.sub.4)--CO--Me 30 81 38 (S) 8
3-C.sub.10H.sub.7--CO--Me 30 61 52 (S) 9 2-C.sub.10H.sub.7--CO--Me
30 73 61 (S) 10 Ph--(CH.sub.2).sub.2--CO--Me 15 91 57 (S) 11
Me--CO-.sup.iPr 15 63 12 (S) .sup.(a)To a mixture of (v) (0.005
mmol) and KOtBu (0.04 mmol) was added a solution of ketone in 6 ml
of iPrOH; .sup.bS/C/B = 200/1/8
[0145] Other A groups of formula (I) can be envisaged such as the
ferrocenyl substituent shown as part of compound 11.
[0146] The above complexes can be prepared using an efficient,
economical, template synthesis utilizing air stable
phosphinoaldehyde precursor. The synthesis of (I) is shown
schematically as follows:
##STR00045##
[0147] It is well known that in the process of hydrogenation or
transfer hydrogenation, imine groups in the catalyst structure can
be reduced to amine groups. These amine-containing catalysts, when
they are soluble, are also active catalysts for the transfer
hydrogenation of ketones under the same conditions as described for
the imine catalysts described here.
[0148] In one embodiment, there is provided a process for the
preparation of a hexa-coordinate iron (II) complex of formula (I),
the process comprising reacting a phosphinaldehyde precursor of
formula (V):
##STR00046##
wherein
[0149] each R.sup.1 is independently selected from the group
consisting of aryl, heteroaryl, C.sub.1-C.sub.8 alkyl,
C.sub.2-C.sub.8 alkenyl, C.sub.1-C.sub.8 alkoxy, aryloxy, and
cycloalkyl, all of which may be optionally substituted; two geminal
R.sup.1 groups may combine to form a C.sub.2-C.sub.4 linear alkyl
diradical or C.sub.3-C.sub.8 branched alkyl diradical, each of
which may be optionally substituted, to form a ring together with
the phosphorus atom to which they are attached; or two R.sup.1
groups, each of which is located on a different phosphorus atom,
may combine to form a linker M, wherein M is selected from the
group consisting of C.sub.2-C.sub.4 linear alkyl diradical and
C.sub.3-C.sub.8 branched alkyl diradical, each of which may be
optionally substituted, or M may be a diradical ligand with a wide
bite angle;
[0150] A is
##STR00047##
[0151] wherein each R.sup.2 and R.sup.3 are independently selected
from the group consisting of H, substituted or unsubstituted
C.sub.1-C.sub.8 alkyl, substituted or unsubstituted C.sub.2-C.sub.8
alkenyl, substituted or unsubstituted aryl, and substituted or
unsubstituted cycloalkyl, and each n is an integer independently
selected from 1, 2, and 3;
[0152] each R.sup.4 is independently selected from the group
consisting of H, substituted or unsubstituted C.sub.1-C.sub.8
alkyl, substituted or unsubstituted C.sub.2-C.sub.8 alkenyl,
substituted or unsubstituted aryl, and substituted or unsubstituted
cycloalkyl;
[0153] with a diamine of formula (VI):
##STR00048##
wherein
[0154] each R.sup.5, R.sup.6, R.sup.7 and R.sup.8 is independently
selected from the group consisting of H, substituted or
unsubstituted C.sub.1-C.sub.8 alkyl, substituted or unsubstituted
C.sub.2-C.sub.8 alkenyl, substituted or unsubstituted aryl, and
substituted or unsubstituted cycloalkyl; R.sup.5 and R.sup.6,
together with the carbon atom to which they are attached, may
combine to form a substituted or unsubstituted cycloalkyl ring of
size from 5-8 carbons; R.sup.7 and R.sup.8, together with the
carbon atom to which they are attached, may combine to form a
substituted or unsubstituted cycloalkyl ring of size from 5-8
carbons; or R.sup.5, R.sup.6, R.sup.7 and R.sup.8, together with
the carbon atoms to which they are attached, may combine to form a
group selected from
##STR00049##
[0155] each of which may be optionally substituted with one or more
substituents selected from the group consisting of C.sub.1-C.sub.8
alkyl, C.sub.1-C.sub.8 alkoxy, and halogen atoms;
[0156] in the presence of:
[0157] an iron (II) salt;
[0158] a ligand selected from the group consisting of CH.sub.3CN;
pyridine and derivatives thereof; and imidazole and derivatives
thereof; and
[0159] a strong base;
[0160] to form the compound of formula (I)
##STR00050##
[0161] wherein A, R.sup.1-R.sup.8, and n are as defined above,
[0162] m is +2,
[0163] L.sup.1 and L.sup.2 are both CH.sub.3CN; pyridine or a
derivative thereof; or imidazole or a derivative thereof;
[0164] and adding at least one counter ion to counterbalance the
charge of the compound of formula (I).
[0165] In one embodiment, the at least one counter ion is selected
from BF.sub.4.sup.-; PF.sub.6.sup.-; SbF.sub.6.sup.-;
ClO.sub.4.sup.-; CH.sub.3SO.sub.3.sup.-; CF.sub.3SO.sub.3.sup.-;
C.sub.6H.sub.5SO.sub.3.sup.-;
p-CH.sub.3C.sub.6H.sub.4SO.sub.3.sup.-; FeCl.sub.4.sup.2-;
FeBr.sub.4.sup.2-; B(R*).sub.4.sup.-, wherein R* is selected from
phenyl, C.sub.6H.sub.3(CF.sub.3).sub.2 and C.sub.6F.sub.5; halides;
pseudohalides; C.sub.1-C.sub.8 alkoxides; and aryloxides. In
another embodiment, the at least one counter ion is BF.sub.4.sup.-.
In another embodiment, the at least one counter ion is
BPh.sub.4.sup.-.
[0166] In another embodiment, the compound of formula (I), wherein
L.sup.1 and L.sup.2 are both CH.sub.3CN, pyridine or a derivative
thereof, or imidazole or a derivative thereof, is further reacted
with CO; hydride; halide ion; NCR, CNR or .sup.-OR, wherein R is
independently selected from the group consisting of aryl,
heteroaryl, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl and
cycloalkyl, all of which may be optionally substituted;
R.sup.aR.sup.bR.sup.cN wherein R.sup.a, R.sup.b, and R.sup.c are
independently selected from the group consisting of H and
C.sub.1-C.sub.2 alkyl; or R.sup.c(CO)R.sup.d wherein R.sup.c and
R.sup.d are independently selected from the group consisting of
C.sub.1-C.sub.8 alkyl, aryl, and heteroaryl, to produce a compound
of formula (VIIIa):
##STR00051##
wherein A, R.sup.1-R.sup.8, and n are as defined for formula
(I),
[0167] L.sub.1 is CH.sub.3CN; pyridine or a derivative thereof; or
imidazole or a derivative thereof; and
[0168] L.sup.2' is selected from the group consisting of CO;
hydride; halide ion; NCR, CNR or .sup.-OR, wherein R is
independently selected from the group consisting of aryl,
heteroaryl, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl and
cycloalkyl, all of which may be optionally substituted;
R.sup.aR.sup.bR.sup.cN wherein R.sup.a, R.sup.b, and R.sup.c are
independently selected from the group consisting of H and
C.sub.1-C.sub.2 alkyl; or R.sup.c(CO)R.sup.d wherein R.sup.c and
R.sup.d are independently selected from the group consisting of
C.sub.1-C.sub.8 alkyl, aryl, and heteroaryl,
and m is +1 or +2.
[0169] In another embodiment, there is provided a process for the
preparation of a hexa-coordinate iron (II) complex, the process
comprising reacting a phosphinaldehyde precursor of formula
(V):
##STR00052##
wherein
[0170] each R.sup.1 is independently selected from the group
consisting of aryl, heteroaryl, C.sub.1-C.sub.8 alkyl,
C.sub.2-C.sub.8 alkenyl, C.sub.1-C.sub.8 alkoxy, aryloxy, and
cycloalkyl, all of which may be optionally substituted; two geminal
R.sup.1 groups may combine to form a C.sub.1-C.sub.4 linear alkyl
diradical or C.sub.3-C.sub.8 branched alkyl diradical, each of
which may be optionally substituted, to form a ring together with
the phosphorus atom to which they are attached; or two R.sup.1
groups, each of which is located on a different phosphorus atom,
may combine to form a linker M, wherein M is selected from the
group consisting of C.sub.2-C.sub.4 linear alkyl diradical and
C.sub.3-C.sub.8 branched alkyl diradical, each of which may be
optionally substituted, or M may be a diradical ligand with a wide
bite angle;
A is
##STR00053##
[0171] wherein each R.sup.2 and R.sup.3 are independently selected
from the group consisting of H, substituted or unsubstituted
C.sub.1-C.sub.8 alkyl, substituted or unsubstituted C.sub.2-C.sub.8
alkenyl, substituted or unsubstituted aryl, and substituted or
unsubstituted cycloalkyl, and each n is an integer independently
selected from 1, 2, and 3;
[0172] each R.sup.4 is independently selected from the group
consisting of H, substituted or unsubstituted C.sub.1-C.sub.8
alkyl, substituted or unsubstituted C.sub.2-C.sub.8 alkenyl,
substituted or unsubstituted aryl, and substituted or unsubstituted
cycloalkyl;
with a diamine of formula (VI):
##STR00054##
wherein
[0173] each R.sup.5, R.sup.6, R.sup.7 and R.sup.8 is independently
selected from the group consisting of H, substituted or
unsubstituted C.sub.1-C.sub.8 alkyl, substituted or unsubstituted
C.sub.2-C.sub.8 alkenyl, substituted or unsubstituted aryl, and
substituted or unsubstituted cycloalkyl; R.sup.5 and R.sup.6,
together with the carbon atom to which they are attached, may
combine to form a substituted or unsubstituted cycloalkyl ring of
size from 5-8 carbons; R.sup.7 and R.sup.8, together with the
carbon atom to which they are attached, may combine to form a
substituted or unsubstituted cycloalkyl ring of size from 5-8
carbons; or R.sup.5, R.sup.6, R.sup.7 and R.sup.8, together with
the carbon atoms to which they are attached, may combine to form a
group selected from
##STR00055##
[0174] each of which may be optionally substituted with one or more
substituents selected from the group consisting of C.sub.1-C.sub.8
alkyl, C.sub.1-C.sub.8 alkoxy, and halogen atoms;
[0175] in the presence of:
[0176] an iron (II) salt;
[0177] a ligand selected from the group consisting of CH.sub.3CN;
pyridine and derivatives thereof; and imidazole and derivatives
thereof; and
[0178] a strong base;
[0179] and further reacting the reaction product of the foregoing
steps with CO to produce a compound of formula (VIIIa):
##STR00056##
[0180] wherein A, R.sup.1-R.sup.8, and n are as defined above,
L.sub.1 is CO, L.sup.2' is Br, and m is +1;
[0181] and adding a counter ion to counterbalance the charge of the
compound of formula (VIIIa).
[0182] The synthesis is conducted in an atmosphere of N.sub.2 (1
atm) or Ar (1 atm) or another suitable gas to prevent reaction with
atmospheric oxygen.
[0183] The concentration of the dimer V for use in forming the
complexes disclosed herein can range from 0.5 M to 0.0005 M with a
preferred concentration of 0.03M. The concentration of the diamine
for use in forming the complexes disclosed herein can range from
0.5 M to 0.0005 M with a preferred concentration of 0.03M.
[0184] Suitable iron (II) salts for use in forming the complexes
disclosed herein include [Fe(H.sub.2O).sub.6].sup.2+ with
counterions as noted herein, namely, Fe(BF.sub.4).sub.2;
Fe(PF.sub.6).sub.2; Fe(SbF.sub.6).sub.2; Fe(ClO.sub.4).sub.2;
Fe(MeSO.sub.3).sub.2; Fe(CF.sub.3SO.sub.3).sub.2;
Fe(C.sub.6H.sub.5SO.sub.3).sub.2;
Fe(p-CH.sub.3C.sub.6H.sub.4SO.sub.3).sub.2; FeCl.sub.4.sup.2;
FeBr.sub.4.sup.2; Fe[B(R*).sub.4].sub.2, wherein R* is selected
from phenyl, C.sub.6H.sub.3(CF.sub.3).sub.2 and C.sub.6F.sub.5;
FeX.sub.2 wherein X is a halide or pseudohalide;
Fe[O(C.sub.1-C.sub.8 alkyl)].sub.2; FeSO.sub.4; Fe(NO.sub.3).sub.2;
and Fe[R**C(O)O].sub.2, wherein R** is C.sub.1-C.sub.8 alkyl,
CF.sub.3, or phenyl, and hydrates thereof. The preferred range of
iron concentrations for the template synthesis of complex II is 1 M
to 0.001 M with a preferred concentration of 0.05 M
[0185] Suitable strong bases for use in forming the complexes
disclosed herein include alkoxides, such as NaOMe, DBU, a
phosphazene, or an alkaline or alkaline-earth metal carbonate salt,
carboxylate salt, alkoxide salt or hydroxide salt. In one
embodiment, the strong base may be MOR***, wherein M is an alkaline
metal selected from Na and K, and R*** is C.sub.1-C.sub.4 alkyl.
The preferred base to iron ratio is 1.3:1.
[0186] Suitable solvents for forming the complexes disclosed herein
include MeOH, EtOH, PrOH, iPrOH, BuOH, CH.sub.3CN, EtCN, pyridine,
picoline, imidazole, methylimidazole. The preferred solvents are
alcoholic solvents, such as MeOH. The preferred total volume of the
solvent in the synthesis ranges from 1 mL to 20,000 mL with a
preferred volume of 10 mL.
[0187] The temperature for the template synthesis can range between
0.degree. and 120.degree. C. with the preferred temperature being
between 20.degree. C. and 40.degree. C.
[0188] The catalysts disclosed herein comprising a compound of
formula (I) and with L.sup.1=L.sup.2=MeCN are surprisingly active
and selective for the hydrogenation, by use of hydrogen gas, of
ketones to produce valuable chiral and non-chiral alcohols in the
presence of a base and an appropriate solvent. The use of complex
(i) provides a particularly active and usefully enantioselective
catalyst system.
[0189] The hydrogenation reaction involving a catalyst disclosed
herein may or may not require solvent. When the use of the solvent
is preferred for practical reasons, any solvent can be utilized for
better performance of the catalyst. Non-limiting examples include
primary, secondary and tertiary alcohols with hydrocarbon skeleton
containing 2-15 carbons or aromatic solvents or ethers or
hydrocarbon solvents.
[0190] In the solvent, the catalyst can be used at concentrations
of 0.001 mM to 0.1 mM while the substrate ketone or imine can be
used in concentrations of 2 mM to 10 M. The pressure of hydrogen
gas can range from 0.5 atm to 100 atm with a preferred pressure of
10 atm. Preferred concentrations of catalyst and substrate are 0.8
mM and 0.16 M, respectively, with a ketone to catalyst ratio of
200:1.
[0191] In another embodiment, the phosphinaldehyde precursor
is:
##STR00057##
the diamine is:
##STR00058##
and the product is a compound of formula (I) having the
structure:
##STR00059##
[0192] In one embodiment, the chiral carbon atoms denoted by
asterisks in (III) above both have an R configuration. In another
embodiment, these chiral carbon atoms both have an S
configuration.
[0193] The processes outlined herein generates a catalyst with
sections derived from the precursor diamine (VI) and phosphine (V)
precursor building blocks with the iron ion acting as a template to
orient the precursors to ensure a high yield of the compound of
formula (I). The sections are shown in structure (VII) below:
##STR00060##
[0194] This is an advantage since different catalysts can be
rapidly synthesized from a phosphine precursor and a diamine
precursor with a variety of substitutents, providing flexibility to
appropriately optimize manufacturing costs and end product quality
specifications, such as a high enantiomeric excess. The methods
disclosed herein allow for tuning of the coordinating ligand to
obtain the easy introduction of chiral elements such as
enantiomerically pure diamines into the catalyst because of the
modular nature of the coordinating ligand. As a consequence, the
iron (II) complex with PNNP ligand is easily modified by
introducing substituents to produce a catalyst structure capable of
interaction with a substrate and ensuring selectivity. Where both
enantiomers of these diamines are available, both enantiomers of an
iron catalyst can be easily prepared to hydrogenate a substrate to
either enantiomer of the target molecule.
[0195] The phosphine-aldehyde precursors (V) are prepared by
methods known in the art from commercially available or readily
prepared phosphine starting materials PHR.sup.1.sub.2 or
PCIR.sup.1.sub.2 and compounds XCR.sup.2R.sup.3Y where X is a
halide or tosylate or other good leaving group known in the art and
Y is a formyl group --CHO or a protected formyl group
--CH(OR).sub.2. In addition, a new method for the synthesis of
phosphine-aldehyde precursors of formula (XIII) is outlined below.
The diamines NH.sub.2CR.sup.5R.sup.6CR.sup.7R.sup.8NH.sub.2 are
available from commercial sources.
[0196] A most interesting catalyst has the discrete structure (i),
shown above (also see Example 1). The chiral ligand can have an (R,
R) or (S, S) configuration. To counterbalance the 2+ charge in the
metal complex salt, anions such as BF.sub.4.sup.-, PF.sub.6.sup.-,
SbF.sub.6.sup.-, FeCl.sub.4.sup.2-, FeBr.sub.4.sup.2-,
tetraarylborates where the aryl is Ph,
C.sub.6H.sub.3(CF.sub.3).sub.2 or C.sub.6F.sub.5, or halides or
pseudohalides or alkoxides and others noted above may be used.
[0197] Catalysts of structure (i), for example the
tetraphenylborate salt, are prepared in a similar fashion to that
of other iron complexes reported by Mikhailine et al. (Mikhailine
et al. "Template Syntheses of Iron(II) Complexes Containing Chiral
P--N--N--P and P--N--N Ligands," Inorg. Chem. 47 (2008), pp
6587-6589) by the template reaction of the phosphonium salt shown
below with (R,R)-dpen as described in Example 1: (S,S)-dpen can
alternatively be used to generate the other enantiomer of (i).
##STR00061##
[0198] The complexes are precipitated as the BPh.sub.4.sup.- salts
in high yield and characterized by NMR, electrospray ionization
mass spectrometry, and elemental analysis. The detailed procedure
of the complex (i) preparation is described as Example 1.
[0199] The reaction of complex I where L.sup.1=L.sup.2=acetonitrile
or another nitrogen donor ligand such as imidazole or pyridine with
carbon monoxide yields the monocarbonyl catalysts of formula
(VIII).
##STR00062##
[0200] For example when complex (i) in acetone is treated with 5
atm CO, the monocarbonyl complex (ii) is formed (see Example 2).
When the complex trans-[Fe(NCMe).sub.2(9)](BF.sub.4).sub.2
(Sui-Seng et al., "Highly Efficient Catalyst Systems Using Iron
Complexes with a Tetradentate PNNP Ligand for the Asymmetric
Hydrogenation of Polar Bonds." Angew. Chem. Int. Ed. Engl. 47
(2008), pp. 940-943) in acetone is reacted with 1 atm CO, the
carbonyl complex trans-[Fe(NCMe)(CO)(9)](BF.sub.4).sub.2 (iii) is
formed (see Example 4). Similarly when
[Fe(NCMe).sub.2(9)](BF.sub.4).sub.2 in acetone is reacted with
tertiary-butylisocyanide, the complex
[Fe(NCMe)(CN.sup.tBu)(9)](BF.sub.4).sub.2 (iv) is formed (see
Example 5). The reaction of complex (vi) (Mikhailine et al.
"Template Syntheses of Iron(II) Complexes Containing Chiral
P--N--N--P and P--N--N Ligands," Inorg. Chem. 47 (2008), pp
6587-6589) (Example 8) with CO produces the complex (vii; Example
9).
##STR00063##
[0201] If the compound of formula (I) is reacted with carbon
monoxide prior to the addition of a counterion and isolation of the
iron (II) complex, this yields the compounds of formula (VIIIa)
##STR00064##
[0202] wherein A, R.sup.1-R.sup.8, and n are as defined for formula
(I), L.sub.1 is CO, L.sup.2' is Br, and m is +1. A counter ion is
then added to counterbalance the charge of the compound of formula
(VIIIa). These iron (II) complexes have been found to be
catalytically active.
[0203] Complex vi has less than optimum activity (<5%
conversion) for the hydrogenation of acetophenone at 35.degree. C.,
25 atm H.sub.2 with KOtBu in iPrOH, and is inactive for the
transfer hydrogenation of ketones in basic isopropanol.
[0204] Catalyst (vii) can be used for transfer hydrogenation. In
the N.sub.2 glovebox, the iron complex (vii) (8.7 mg, 0.007 mmol),
KO.sup.tBu (6.3 mg, 0.056 mmol) and acetophenone (168 mg, 1.4 mmol)
were separately dissolved in the 3 mL of 2-propanol, each. The
resulting solutions were added to a vial charged with a stirring
bar in the order: substrate, catalyst followed by base and stirred
at room temperature. The samples of the reaction mixture were
analyzed by GC. The conversion was 92% after 75 minutes.
[0205] Complex trans-[Fe(MeCN).sub.2(6)](BF.sub.4).sub.2 (Example
10) wherein 6 is,
##STR00065##
n=2, was prepared and tested. For the hydrogenation of acetophenone
with H.sub.2 (25 atm) with a catalyst to base to substrate ratio of
1:15:225 in isopropanol the conversion was 4% after 18 h. It was
found to be inactive for the transfer hydrogenation of acetophenone
in basic isopropanol under the standard conditions.
[0206] The iron (II) complex
trans-[Fe(MeCN).sub.2(6)](BF.sub.4).sub.2, can be reacted with CO
to produce
##STR00066##
[0207] Catalyst (viii) can be used for transfer hydrogenation. To a
mixture of (viii) (0.005 mmol) and KOtBu (0.04 mmol) was added a
solution of ketone in 6 ml of .sup.iPrOH. Catalyst (viii) was found
to be highly active for the transformation of acetophenone to
1-phenylethanol at room temperature using a catalyst:base:substrate
ratio of 1:8:600 (85% conversion after 60 min).
[0208] The bis-acetonitrile complexes
trans-[Fe(NCMe).sub.2{9)}][BF.sub.4].sub.2,
trans-[Fe(MeCN).sub.2(6)](BF.sub.4).sub.2, wherein 6 is
##STR00067##
where n=2 and
trans-[Fe(NCMe).sub.2{(R,R)--PPh.sub.2C.sub.6H.sub.4CHNCHPhCHPhNCHC.sub.6-
H.sub.4PPh.sub.2}][BF.sub.4].sub.2 were prepared by reaction of the
known PNNP ligands 6 (Jeffery, J. C.; Rauchfuss, T. B.; Tucker, P.
A. Inorg. Chem. 1980, 19, 3306-3316) 9, and
PPh.sub.2C.sub.6H.sub.4CHNCHPhCHPhNCHC.sub.6H.sub.4PPh.sub.2 (J.-X.
Gao et al. Chirality 2000, 12, 383) with iron salts such as
[Fe(OH.sub.2).sub.6](BF.sub.4).sub.2 in acetonitrile as described
in the examples below.
[0209] The iron complexes trans-[Fe(NCMe)(CO)(6)][BF.sub.4],
(R,R)-- or (S,S)-trans-[Fe(NCMe)(CO){9)}][BF.sub.4].sub.2 and
(R,R)-- or (S,S)--
trans-[Fe(NCMe)(CO)(PPh.sub.2C.sub.6H.sub.4CHNCHPhCHPhNCHC.sub.6H.sub.4PP-
h.sub.2)][BF.sub.4].sub.2 were obtained as orange solids in good
yields when the corresponding bis-acetonitrile compounds just
mentioned were stirred under a CO atmosphere in acetone. The new
compounds are fairly air stable, both as a solid and in solution.
They are soluble in acetonitrile and methylenechloride, poorly
soluble in acetone, chloroform, 2-propanol and insoluble in
tetrahydrofuran, ether and hydrocarbons. The new compounds were
characterized by .sup.1H and .sup.13C and .sup.31P NMR techniques,
elemental analysis, mass spectroscopy, IR and the solid state
structures were confirmed by X-ray crystallography. The
.sup.31P{.sup.1H} NMR spectrum of
trans-[Fe(NCMe)(CO)(6)][BF.sub.4].sub.2 shows a singlet while those
for (R,R)-- or (S,S)-trans-[Fe(NCMe)(CO){9)}][BF.sub.4].sub.2 and
(R,R)-- or (S,S)--
trans-[Fe(NCMe)(CO)(PPh.sub.2C.sub.6H.sub.4CHNCHPhCHPhNCHC.sub.6H-
.sub.4PPh.sub.2)][BF.sub.4].sub.2 show two doublets. Mass spectra
(ESI) show the cationic fragment without the acetonitrile and
carbonyl ligands.
[0210] In one embodiment, there is provided a process for preparing
an alcoholic compound wherein said process comprises a step of
preparing the alcoholic compound by reducing a ketone or aldehyde
with the reaction of hydrogen or a compound donating hydrogen in
the presence of a hexa-coordinate iron (II) complex of formula (I),
with the proviso that the ketone is not an unsubstituted
cycloalkanone.
[0211] As can be seen from Table 3, no conversion was observed for
the transfer hydrogenation of cyclohexanone catalyzed by (iii).
However, it is envisioned that cyclic ketones having substituents
such as aromatic groups may be better substrates.
[0212] In another embodiment, the hexa-coordinate iron (II) complex
comprises a compound of formula (I) having the structure:
##STR00068##
[0213] In another embodiment, the chiral carbons atoms denoted by
asterisks both have an R configuration. In another embodiment, the
chiral carbons atoms denoted by asterisks both have an S
configuration, In another embodiment, the reaction uses
hydrogen.
[0214] In yet another embodiment, the substrate is a ketone. In
another embodiment, the ketone is an aromatic ketone. In yet
another embodiment, the ketone is prochiral.
[0215] In another embodiment, there is provided a process for
preparing an amine compound wherein said process comprises a step
of preparing the amine compound by reducing an imine with the
reaction of hydrogen or a compound donating hydrogen in the
presence of a hexa-coordinate iron (II) complex of formula (I). In
another embodiment, the hexa-coordinate iron (II) complex comprises
a compound of formula (I) having the structure:
##STR00069##
[0216] In another embodiment, the chiral carbons atoms denoted by
asterisks both have an R configuration. In another embodiment, the
chiral carbons atoms denoted by asterisks both have an S
configuration. In another embodiment, the reaction uses a compound
donating hydrogen. In another embodiment, the imine is not
prochiral.
[0217] The catalysts I disclosed herein can reduce aldehydes,
ketones and imines with general structure (IX):
##STR00070##
[0218] where the R', R'' symbols, taken separately, represent
simultaneously or independently a hydrogen atom, a linear or
branched alkyl or alkenyl chain containing 1-8 carbon atoms,
possibly substituted, a cycloalkyl radical or an aryl group,
possibly substituted. The symbol Q represents simultaneously or
independently an oxygen atom or NR''' group, where R''' symbol
represent simultaneously or independently a hydrogen atom, a linear
or branched alkyl or alkenyl chain containing 1-8 carbon atoms,
possibly substituted, a cycloalkyl radical or an aryl group,
possibly substituted. Possible substituents include alkyl groups
(such as C.sub.1-C.sub.8 alkyl), aryl groups, halogens, and alkoxy
groups.
[0219] The reduction of ketones and imines with general structure
(IX) produce products, namely alcohols and amines, respectively
with general structure (X). When the correct asymmetric
hydrogenation or transfer hydrogenation catalyst I is applied, the
products are obtained in one enantiomeric form. For example the use
of complex (i) in asymmetric hydrogenation gives the S-alcohol in
high e.e. while the use of complex (ii) or (v) in asymmetric
transfer hydrogenation gives the S-alcohol in high e.e. The correct
catalyst I might also be used for other catalytic asymmetric
reactions such as the transfer of hydrogen from a hydrogen donor
such as isopropanol or ethanol to a ketone or imine. The use of the
catalysts disclosed herein for addition of a hydrosilane to a
ketone or imine, an asymmetric Michael addition of donor to an
acceptor, an asymmetric Diels-Alder reaction of an olefin to a
diene or an asymmetric cyclopropanation reaction may also be
possible.
##STR00071##
[0220] The catalysts disclosed herein comprising a compound of
formula (I) and with L.sup.1=L.sup.2=MeCN are surprisingly active
and selective for the hydrogenation, by use of hydrogen gas, of
ketones to produce valuable chiral and non-chiral alcohols in the
presence of a base and an appropriate solvent. The use of complex
(i) provides a particularly active and usefully enantioselective
catalyst system.
[0221] The hydrogenation reaction involving a catalyst disclosed
herein may or may not require solvent. When the use of the solvent
is preferred for practical reasons, any solvent can be utilized for
better performance of the catalyst. Non-limiting examples include
primary, secondary and tertiary alcohols with hydrocarbon skeleton
containing 2-15 carbons or aromatic solvents or ethers or
hydrocarbon solvents.
[0222] In the solvent, the catalyst can be used at concentrations
of 0.001 mM to 0.1 mM while the substrate ketone or imine can be
used in concentrations of 2 mM to 10 M. The pressure of hydrogen
gas can range from 0.5 atm to 100 atm with a preferred pressure of
10 atm. Preferred concentrations of catalyst and substrate are 0.8
mM and 0.16 M, respectively, with a ketone to catalyst ratio of
200:1.
[0223] The base in the hydrogenation process using H.sub.2 gas can
be substrate (if it has a basic functionality) or a strong neutral
base such as DBU or a phosphazene, or an alkaline or alkaline-earth
metal carbonate salt, carboxylate salt, alkoxide salt or hydroxide
salt. The base in the process can be used in a concentration of
between one and fifty times the concentration of the catalyst
concentration. The preferred base to catalyst ratio is 15.
[0224] The temperature of the direct hydrogenation with hydrogen
gas catalyzed by complexes comprising a compound of formula (I) and
with L.sup.1=L.sup.2=MeCN can range between 0.degree. and
120.degree. C. with the preferred temperature being 35.degree.
C.
[0225] Catalysts such as (ii) are particularly active and selective
for the asymmetric transfer hydrogenation of ketones to non racemic
alcohols in basic isopropanol solvent or other alcohols or mixtures
such as formic acid/triethylamine known in the art to transfer
hydrogen. Similarly, complexes (iii), (iv) and (v) can also be used
as catalysts for the asymmetric transfer hydrogenation of ketones
and the transfer hydrogenation of certain imines. The catalysts
(VIII) with the ligand L.sup.1=MeCN or another nitrile donor ligand
and L.sup.2=CO are surprisingly active and selective for the
reduction of ketones to non-racemic alcohols by transfer of
hydrogen from basic isopropanol or other alcohols or mixtures such
as formic acid/triethylamine known in the art to transfer
hydrogen.
[0226] The conditions for the transfer hydrogenation catalyzed by
catalysts (ii), (iii), (iv), (v) and of the type (VIII) are
surprising mild. The preferred temperature is room temperature but
a range of temperatures is possible from 0.degree. and 150.degree.
C. The turnover numbers reported in the examples are unprecedented
for non-PGM catalysts that operate at room temperature.
[0227] The transfer hydrogenation catalysts (ii), (iii), (iv), (v)
and of the type (VIII) can be used at concentrations of 0.001 mM to
1 mM while the substrate ketone or imine can be used in
concentrations of 2 mM to 5 M. Preferred concentrations of catalyst
and substrate are 0.1 mM and 0.2 M, respectively, with a ketone to
catalyst ratio of 1600:1 for catalyst (ii) and 200:1 for catalyst
(iii) and 600:1 for catalyst (v) or in general a substrate to
catalyst ratio of 500:1.
[0228] The base in the transfer hydrogenation process can be
substrate (if it has a basic functionality) or a strong neutral
base such as DBU or a phosphazene, or an alkaline or alkaline-earth
metal carbonate salt, carboxylate salt, alkoxide salt or hydroxide
salt. The base in the process can be used in a concentration of
between one and fifty times the concentration of the catalyst
concentration. The preferred base to catalyst ratio is 8.
[0229] A new method of synthesizing phosphonium dimers has been
developed. It has been found that such phosphonium dimers can be
synthesized by the direct reaction of an alkyl-substituted
secondary phosphine with organic compounds containing both a
protected aldehyde and a carbon-halogen bond according to the
general reaction scheme shown below.
##STR00072##
[0230] A process for preparing a phosphonium dimer of formula
(XIII) is provided:
##STR00073##
[0231] wherein R.sup.1 is selected from the group consisting of
C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 substituted alkyl,
cycloalkyl, and substituted cycloalkyl, and X is selected from the
group consisting of Br and I, the process comprising:
reacting a compound of formula (XI):
HPR.sup.1.sub.2 (XI)
[0232] wherein R.sup.1 is as defined above; with a compound of
formula (XII):
##STR00074##
wherein X is as defined above, and R.sup.e is C.sub.1-C.sub.8
alkyl, or the two Re can combine to form a C.sub.2-C.sub.3 linear
alkyl diradical; and heating the reaction product in the presence
of water to form the phosphonium dimer of formula (XIII).
[0233] R.sup.1 is an electron-donating alkyl substituent, and in
one embodiment the two R.sup.1 groups on each phosphorus atom may
be different. R.sup.e may be, for example, Me, Et, Pr etc. or
(R.sup.e).sub.2=--CH.sub.2CH.sub.2--.
[0234] Cyclic phosphonium dimers V with A=CH.sub.2 and R.sup.4=H
and with R.sup.1=cyclohexyl (Example 15) isopropyl (Example 21) or
ethyl (Example 22) substituents at the phosphorus atoms were
prepared in a new, direct reaction of the secondary phosphine with
the protected bromoacetoaldehyde diethyl acetal
(BrCH.sub.2CH(OEt).sub.2) in THF, neat or in other organic solvents
that dissolve the compounds to give an intermediate phosphonium
salt that was then hydrolyzed. The yields of the white solids are
80, 81 and 40%, respectively. The cyclohexyl and isopropyl
compounds are air- and moisture-stable white solids that are
soluble in methanol or/and water and insoluble in other common
organic solvents. They possess similar physical properties to that
of the dimer with phenyl groups on phosphorus. The dimer with ethyl
groups, on the other hand, adsorbs water on prolonged exposure to
atmosphere, and is soluble only in water. However an aqueous
solution of this compound is stable toward oxidation by molecular
oxygen.
[0235] The new dimers were fully characterized by NMR spectroscopy
and X-ray diffraction experiments. These compound show two
characteristic singlets in the .sup.31P{.sup.1H} NMR spectra in the
region between 11 and 40 ppm and a multiplet in the region between
5.3 and 6.2 ppm for the proton on the carbon with the hydroxyl
group --CH(OH)--, a downfield shift of the aldehyde hydrogen
resonance which is expected in the 9-10 ppm region. The two
singlets observed in the .sup.31P{.sup.1H}NMR arise from the rac
and meso diastereomers.
[0236] The invention will now be described in further detail by way
of the following examples, wherein the temperatures are indicated
in degrees centigrade and the abbreviations have the usual meaning
in the art.
EXAMPLES
General Considerations
[0237] All preparations and manipulations were carried out under an
argon or nitrogen atmosphere using standard Schlenk, vacuum-line,
and glove-box techniques. Dry, oxygen-free solvents were prepared
by distillation from appropriate drying agents and employed
throughout. The synthesis of the ligands (R,R)-cyP.sub.2N.sub.2 (9)
and
(R,R)--PPh.sub.2C.sub.6H.sub.4CHNCHPhCHPhNCHC.sub.6H.sub.4PPh.sub.2
have been reported previously (J.-X. Gao, H. Zhang, X.-D. Yi, P.-P.
Xu, C.-L. Tang, H.-L. Wan, K.-R. Tsai, T. Ikariya, Chirality 2000,
12, 383). All other reagents used in the experiments were obtained
from commercial sources and used as received. The mass spectroscopy
(ESI.sup.+, MeOH) and elemental analyses were performed at the
University of Toronto, on sample handled under argon for the EA.
Varian Gemini 400 MHz and 300 MHz spectrometers were employed for
recording .sup.1H (400 MHz and 300 MHz), .sup.13C{.sup.1H} (100 MHz
and 75 MHz), and .sup.31P{1H} (161 MHz and 121 MHz) NMR spectra at
ambient temperature. The .sup.1H and .sup.13C NMR spectra were
referenced to solvent resonances, as follows: 7.26 and 77.16 ppm
for CHCl.sub.3 and CDCl.sub.3, 1.94 and 1.24 ppm for CH.sub.3CN and
CD.sub.3CN). The .sub.31P NMR spectra were referenced to 85%
H.sub.3PO.sub.4 (0 ppm). All infrared spectra were recorded on a
Nicolet 550 Magna-IR spectrometer.
[0238] The samples of hydrogenation reaction mixtures were analyzed
by .sup.1H NMR spectroscopy and GC using a Perkin Elmer Autosystem
XL chromatograph with a chiral column (CP chirasil-Dex CB 25
m.times.2.5 mm). Hydrogen was used as a mobile phase at a column
pressure of 6 psi. The injector temperature was 250.degree. C., and
a FID temperature was 275.degree. C. The retention times of the
substrates are listed in Table 5.
[0239] trans-4-phenyl-3-buten-2-one: the GC analysis were conducted
as above, except that for the GC conditions the oven temperature
was 140.degree. C. The retention times were
trans-4-phenyl-3-buten-2-one 7.8 min, I-4-phenyl-2-butanol 11.1
min, (S)-4-phenyl-2-butanol 11.4 min, trans-4-phenyl-3-buten-2-one
13.4 min, trans-(R)-4-phenyl-3-buten-2-ol 15.9 min,
trans-(S)-4-phenyl-3-buten-2-ol 16.2 min. The product was also
identified by 1H NMR spectroscopy and the data obtained matches
literature values.
[0240] N-Benzylideneaniline and benzophenone: the conversion of the
product was determined by 1H NMR spectroscopy and the data matches
those of the commercial samples.
[0241] General procedure for the iron catalyzed
H.sub.2-hydrogenation of polar bonds: In an Ar or N.sub.2 glovebox,
the iron complex (8 mg, 0.008 mmol) was suspended in 2 mL of
2-propanol and acetophenone (225 equiv) in 1 mL of 2-propanol. The
solution of base was prepared by dissolution of KOtBu (15 equiv) in
2 mL of 2-propanol. The solution containing the substrate and then
the one with base, followed by the suspension of catalyst were
injected into a 50 cm.sup.3 Parr hydrogenator reactor filled with
hydrogen at the desired pressure and temperature, maintained by use
of a Fischer Scientific Isotemp 1016D water bath.
[0242] The procedures for the iron catalyzed transfer hydrogenation
of polar bonds are found in the footnotes of the Tables above.
TABLE-US-00005 TABLE 5 GC analytical data for the reduced
substrates (t.sub.s = retention time of substrate; t.sub.1, t.sub.2
= retention times of the products) Oven Temp. Substrate (.degree.
C.) t.sub.s (min) t.sub.1 (min) t.sub.2 (min) Ph--CO--Me 130 5.0
8.5 9.1 (2'-Cl--C.sub.6H.sub.4)--CO--Me 145 4.7 10.0 11.7
(3'-Cl--C.sub.6H.sub.4)--CO--Me 130 7.8 16.6 17.7
(4'-Cl--C.sub.6H.sub.4)--CO--Me 145 5.9 11.1 12.0
(4'-Br--C.sub.6H.sub.4)--CO--Me 155 6.5 11.4 12.1
(4'-Me--C.sub.6H.sub.4)--CO--Me 125 6.5 9.6 10.4
(4'-OMe--C.sub.6H.sub.4)--CO--Me 130 15.6 21.8 23.2 Ph--CO--Et 105
18.4 48.5 51.5 C.sub.10H.sub.7--CO--Me.sup.[a] 150 21.8 35.7 37.5
C.sub.10H.sub.7--CO--Me.sup.[b] 140 24.1 63.6 73.9 Ph--CHO 130 3.9
5.9 -- Ph--CO--iPr 114 11.0 37.2 37.8
Ph--CH.sub.2--CH.sub.2--CO--Me 135 7.9 11.8 12.6 Ph--CO--tBu 140
5.9 11.6 12.2 CH.sub.3--CO--CH--(CH.sub.3).sub.2 60 2.9 8.2 8.5
.sup.[a]2-acetonaphthone. .sup.[b]1-acetonaphthone
Example 1
Preparation of the catalyst (R,
R)--[Fe(Ph.sub.2PCH.sub.2CH.dbd.NCH(Ph)CH(Ph)N.dbd.CHCH.sub.2PPh.sub.2)(C-
H.sub.3CN).sub.2][BPh.sub.4].sub.2, (i)
##STR00075##
[0243] Synthesis of the Diphenylphosphino-Acetaldehyde Hydrobromide
Dimer
[0244] The procedure for the synthesis of the
diphenylphosphino-acetaldehyde hydrobromide dimer has been
previously reported by Matt et al. (Matt, D.; Ziessel, R.; De Cian,
A.; Fischer, J. New J. Chem. 1996, 20, 1257-1263) and was used in
this study with modifications. Potassium hydride (413 mg, 10.3
mmol) was partially dissolved in 10 mL of dry THF.
Diphenylphosphine (1.60 g, 8.58 mmol) was added to the resulting
mixture to give a purple solution. After 30 min the solution was
cooled to -78.degree. C. and bromoacetaldehyde diethyl acetal
(1.691 g, 8.58 mmol) was added over the course of 15 min. The
mixture was brought to room temperature to give a yellow solution.
A diluted hydrobromic acid (10 mL, 1.17 mol_L-1) were added and the
mixture was heated at 40.degree. C. overnight. The solvent volume
was reduced by one half. The white precipitate was recovered by
filtration and washed with 20 mL of water and 20 mL
cyclohexane:ethyl acetate (1:1 by volume). Drying in vacuo yielded
4 (2.51 g, 4.06 mmol) as a white powder. Analytical data were the
same as those that have been reported by Matt et al.
Synthesis of the catalyst (R,
R)--[Fe(Ph.sub.2PCH.sub.2CH.dbd.NCH(Ph)CH(Ph)N.dbd.CHCH.sub.2PPh.sub.2)(C-
H.sub.3CN).sub.2][BPh.sub.4].sub.2, (i)
[0245] The diphenylphosphino-acetaldehyde hydrobromide dimer (200
mg, 0.324 mmol) was completely dissolved in MeOH (6 mL).
[Fe(H.sub.2O).sub.6][BF.sub.4].sub.2 (164 mg, 0.485 mmol) was added
to the reaction mixture. NaOMe (34.9 mg, 0.647 mmol) was added as a
MeOH (1 mL) solution and the color of the solution changed from
colorless to clear yellow. After 10 min of stirring, 1 mL of
acetonitrile was added. To this solution was added, over the course
of 20 min, a solution of (1R,2R)-(+)-1,2-diphenylethylenediamine
(R,R-dpen, 69 mg, 0.323 mmol) in 0.5 mL of acetonitrile. The
solution changed color to purple after the addition. After 20 h the
resulting solution was added to a solution of NaBPh.sub.4 (250 mg,
0.658 mmol) in 1 mL of MeOH to cause the formation of the
precipitate. A pink solid was recovered by filtration and dried
under vacuum. Yield of (i): 83% (380 mg); .sup.1H NMR (400 MHz,
CD.sub.3CN) .delta.: 1.54 (s, 6H, CH.sub.3CN), 3.95-4.15 (m, 2H,
HCP), 4.26-4.38 (m, 2H, HCP), 5.43 (m, 2H, HC--N), 6.80-7.75 (m,
70H, ArH), 8.10-8.27 (m, 2H, HC.dbd.N). .sup.31P {H} NMR (121 MHz;
CD.sub.3CN): 72.63 ppm (s). Anal. Calcd for
C.sub.94H.sub.84N.sub.4P.sub.2FeB.sub.2: C, 80.14; H, 6.01; N,
3.98. Found: C, 79.20; H, 6.08; N, 4.65. MS (ESI.sup.+) Calcd for
[C.sub.46H.sub.44N.sub.4P.sub.2Fe-2(CH.sub.3CN)].sup.2+: 344.3 m/z.
Found: 344.1 m/z. MS (ESI.sup.-) Calcd for [B(Ph).sub.4].sup.-:
319.2 m/z. Found: 319.2 m/z.
Example 2
Preparation of the catalyst (R,
R)-[Fe(Ph.sub.2PCH.sub.2CH.dbd.NCH(Ph)CH(Ph)N.dbd.CHCH.sub.2PPh.sub.2)(CH-
.sub.3CN)(CO)][BPh.sub.4].sub.2, (ii)
##STR00076##
[0247] The tetraphenylborate salt of the bisacetonitrile complex
(i) (200 mg, 0.142 mmol) was dissolved in (10 mL) of degassed
acetone under inert atmosphere. Resulting solution was placed in
the CO high pressure reactor and was stirred under 5 atmosphere of
CO for 12 hours at room temperature. Solvent was evaporated under
reduced pressure and resulting solid was washed with diethyl ether
(5 mL) three times. Yellow solid was dried under vacuum. Yield of
(ii): 75% (149 mg); .sup.1H NMR (400 MHz, acetone-d.sub.6) .delta.:
1.54 (s, 3H, CH.sub.3CN), 4.42-4.57 (m, 2H, HC--N), 5.58-5.76 (m,
4H, HCP), 6.80-7.75 (m, 70H, ArH), 8.14-8.23 (m, 2H, HC.dbd.N);
.sup.31P {.sup.1H} NMR (121 MHz; acetone-d.sub.6): 69.3 ppm (d,
J.sub.P-P=30 Hz); 65.7 ppm (d, J.sub.P-P=30 Hz); MS (ESI.sup.+)
Calcd for
[C.sub.46H.sub.44N.sub.4P.sub.2Fe--(CO+CH.sub.3CN)].sup.2+: 344.3
m/z. Found: 344.1 m/z. MS (ESI-) Calcd for [B(Ph).sub.4].sup.-:
319.2 m/z. Found: 319.2 m/z, IR (KBr) 2294 cm.sup.-1
(.upsilon.C.ident.N, MeCN), 2001 cm.sup.-1 (.upsilon.CO).
Example 3
Preparation of the complex [Fe(NCMe).sub.2{9)}][BF.sub.4].sub.2
##STR00077##
[0249] A suspension of (R,R)-cyP.sub.2N.sub.2 (9) (317 mg, 0.48
mmol) in 7 mL of MeCN was added dropwise to a solution of
[Fe(H.sub.2O).sub.6][BF.sub.4].sub.2 (162 mg, 0.48 mmol) in MeCN
(12 mL). After stirring for 20 min at room temperature, the red
solution was concentrated to 1 mL and 10 mL of Et.sub.2O were
added. A red-orange powder precipitated and was isolated by
filtration and washed with Et.sub.2O. Recrystallization of
[Fe(NCMe).sub.2{9}][BF.sub.4].sub.2 from a CHCl.sub.3/ether
solution gave the product (435 mg, 92% yield). A CDCl.sub.3
solution in a NMR tube yielded red crystals suitable for X-ray
diffraction studies and elemental analysis. 1H NMR (400 MHz,
CDCl.sub.3) .delta.=9.26 (s, HC.dbd.N), 8.06-6.63 (m, ArH), 3.68
(s, CH), 2.70-2.13 (m, CH2), 1.75 (s, CH.sub.3CN).
.sup.13C{.sup.1H}NMR (100 MHz, CDCl.sub.3) .delta.: 172.45 (s,
HC.dbd.N), 138.66-124.84 (m, C.sub.aromatic and C.ident.N), 71.52,
66.05 (s, CH), 31.54, 29.26, 24.16, 22.82 (s, CH.sub.2), 1.22 (s,
CH.sub.3CN). .sup.31P{1H} NMR (161 MHz, CDCl.sub.3) .delta.: 53.4
(s) ppm. .sup.31P{1H} NMR (161 MHz, CD.sub.3CN) .delta.: 52.6 (s)
ppm. Anal. Calcd. for
C.sub.48H.sub.46N.sub.4B.sub.2F.sub.8P.sub.2Fe.sub.10.5CHCl.sub.3:
C, 56.55; H, 4.55; N, 5.44. Found: C, 56.45; H, 4.91; N, 5.04. IR
(KBr) 2284 cm.sup.-1 (.upsilon.CEN, MeCN). MS (ESI.sup.+, MeOH) for
[Fe(9)].sup.2+ (m/z=357.1).
Example 4
Preparation of the catalyst [Fe(NCMe)(CO){9}][BF.sub.4].sub.2,
(iii)
##STR00078##
[0251] Method A. A solution of [Fe(MeCN).sub.2{9}][BF.sub.4].sub.2
(Example 3, 200 mg, 0.21 mmol) in acetone (10 mL) was stirred under
2 atm CO overnight at room temperature. The resulting orange-yellow
solution was evaporated to dryness to give an orange powder
(quantitative yield).
[0252] Method B. A solution of [Fe(MeCN).sub.2{9}][BF.sub.4].sub.2
(Example 3, 160 mg, 0.17 mmol) in CHCl.sub.3 (3 mL) was refluxed
under 2 atm CO for 48 hours. The resulting orange-yellow solution
was evaporated to dryness to give an orange powder (iii)
(quantitative yield).
[0253] 1H NMR (400 MHz, CDCl.sub.3) .delta.: 9.11 (s, CH.dbd.N),
8.21-6.35 (m, ArH), 3.53-3.32 (m, CH), 2.77-1.21 (m, CH.sub.2),
1.75 (s, CH.sub.3CN). .sup.13C{.sup.1H}NMR (100 MHz, CDCl.sub.3)
.delta.: 213.75 (t, .sup.2J.sub.C-P=27.2 Hz, CO), 171.87 (d,
.sup.3J.sub.C-P=25.3 Hz, HC.dbd.N), 139.42-123.85 (m, Caromatic and
C.ident.N), 70.56, 65.99 (s, CH), 32.22, 30.89, 24.36, 23.71 (s,
CH.sub.2), 1.03 (s, CH.sub.3CN). .sup.31P{.sup.1H} NMR (161 MHz,
CDCl.sub.3) .delta.: 51.82 (d, .sup.2J.sub.P-P=40.6 Hz), 48.03 (d,
.sup.2J.sub.P-P=40.6 Hz). Anal. Calcd. for
C.sub.47H.sub.43N.sub.3OB.sub.2F.sub.8P.sub.2Fe.0.25CHCl.sub.3: C,
57.49; H, 4.42; N, 4.26. Found: C, 57.36; H, 4.99; N, 4.10. IR
(KBr) 2294 cm-1 (.upsilon.C.ident.N, MeCN), 1999 cm-1
(.upsilon.CO). MS (ESI.sup.+, MeOH) for [Fe{9}].sup.2+
(m/z=357.1).
Example 5
Preparation of the catalyst
[Fe(NCMe)(CN.sup.tBu){9}][BF.sub.4].sub.2, (iv)
##STR00079##
[0255] A solution of [Fe(MeCN).sub.2{9}][BF.sub.4].sub.2 (Example
3; 95 mg, 0.098 mmol) and tBuNC (22 .mu.L, 0.196 mmol) in acetone
(3 mL) was stirred for 2 h at room temperature. The resulting
orange-yellow solution was evaporated to dryness to give an orange
powder of (iv). (quantitative yield). .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta.: 9.27, 8.87 (s, CH.dbd.N), 8.30-6.55 (m, ArH),
3.71-1.58 (m, CH and CH.sub.2), 2.17 (s, CH.sub.3CN), 1.21 (s,
(CH.sub.3).sub.3CNC). .sup.13C{.sup.1H}NMR (100 MHz, CDCl.sub.3)
.delta.: 173.47, 171.62 (s, HC.dbd.N), 139.60-125.38 (m,
C.sub.aromatic, C.ident.N and N.dbd.C), 75.8, 73.61 (s, CH), 32.38,
31.76, 24.76, 23.90 (s, CH.sub.2), 29.45 (s, (CH.sub.3).sub.3CNC),
1.03 (s, CH.sub.3CN). .sup.31P{.sup.1H}NMR (161 MHz, CDCl.sub.3)
.delta.: 58.22 (d, .sup.2J.sub.P-P=51 Hz), 48.48 (d,
.sup.2J.sub.P-P=51 Hz). IR (KBr) 2151, 2173 cm.sup.-1
(.upsilon.C.ident.N, MeCN and tBuNC).
Example 6
Preparation of
trans-[Fe(NCMe).sub.2{(R,R)--PPh.sub.2C.sub.6H.sub.4CHNCHPhCHPhNCHC.sub.6-
H.sub.4PPh.sub.2}][BF.sub.4].sub.2
[0256] A solution of
(R,R)--PPh.sub.2C.sub.6H.sub.4CHNCHPhCHPhNCHC.sub.6H.sub.4PPh.sub.2
(510 mg, 0.78 mmol) and [Fe(H.sub.2O).sub.6][BF.sub.4].sub.2 (260
mg, 0.78 mmol) in MeCN (10 mL) was stirred for 1 h at ambient
temperature. The solution was evaporated and the remaining red
residue was washed with pentane. The analytically pure product was
obtained after crystallization from MeCN/Et2O as dark red crystals
(510 mg, 64%). Recrystallization from a MeCN/MeOH/Et2O solution
yielded crystals suitable for X-ray diffraction studies. 1 H NMR
(400 MHz, CD3CN): 9.32 (s, CH.dbd.N), 7.82-7.21 (m, Ar--H), 6.94
(m, Ar--H), 6.85 (m, Ar--H, 5.97 (s, N--CH), 1.96 (s, CH3CN).
31P{1H} NMR (161 MHz, CDCl3): 51.8 (s). Anal. Calcd for C56 H48 N4
B2 F8 P2 Fe: C, 62.95; H, 4.53; N, 5.24. Found: C, 62.69; H, 4.79;
N, 5.81.
Example 7
Preparation of catalyst (v):
trans-[Fe(NCMe)(CO){(R,R)--PPh.sub.2C.sub.6H.sub.4CHNCHPhCHPhNCHC.sub.6H.-
sub.4PPh.sub.2}][BF.sub.4].sub.2
##STR00080##
[0258] A solution of
trans-[Fe(NCMe).sub.2{(R,R)--PPh.sub.2C.sub.6H.sub.4CHNCHPhCHPhNCHC.sub.6-
H.sub.4PPh.sub.2}][BF.sub.4].sub.2 (0.51 g, 0.5 mmol) in acetone
was stirred under a 5 atm of CO at room temperature for 6 h. The
solvents were evaporated, to obtain an orange powder. The powder
was again dissolved in acetone and stirred under two atm of CO
atmosphere for 12 h at room temperature. The solvents were
evaporated and the remaining orange residue was washed with toluene
and ether. Crystallization from acetone/CH.sub.2Cl.sub.2/Et.sub.2O
gave the analytical pure compound as an orange solid. Yield: 0.47 g
(0.4 mmol, 80%). .sup.1H NMR (d.sup.3-MeCN, 300 MHz, 25.degree.
C.): 6.05 (br s, 2H, CH), 6.69-8.06 (several m, 30H, Ph), 9.43 (br
s, 2H, CH.dbd.N). .sup.31P NMR (CD.sub.2Cl.sub.2, 121 MHz): 49.9
(d, J.sub.P,P=39 Hz), 53.0 (d, J.sub.P,P=39 Hz). Anal. Calcd. for
C.sub.55H.sub.45B.sub.2F.sub.8N.sub.3P.sub.2Fe.sub.1: C, 62.59; H,
4.30; N, 3.98. Found: C, 61.93; H, 4.96; N, 3.67.
Example 8
Preparation of catalyst(vi):
Fe(Ph.sub.2PCH.sub.2CH.dbd.NC.sub.2H.sub.4N.dbd.CHCH.sub.2PPh.sub.2)(CH.s-
ub.3CN).sub.2](BPh.sub.4).sub.2]
##STR00081##
[0260] Preparation of precursor solution (A): The reaction was
performed in the glove-box under N.sub.2 atmosphere at room
temperature. The diphenylphosphino-acetaldehyde hydrobromide dimer
from Example 1 (200 mg, 0.324 mmol) was partially dissolved in
CH.sub.3CN (6 mL). After 5 min of stirring
[Fe(H.sub.2O).sub.6][BF.sub.4].sub.2 (164 mg, 0.485 mmol) was added
to the reaction mixture. t-BuOK (74.0 mg, 0.645 mmol) was added to
the reaction mixture and the color of the solution changed from
white to yellow. The mixture was stirred at room temperature for 30
min without any observable changes.
[0261] A stock solution of the diamine was prepared by dissolving
85.5 mg of 1,2-ethylenediamine in 1.1 mL of acetonitrile. A portion
(0.250 mL) of stock solution was added to the precursor solution
(A) over the course of 20 min at room temperature. The solution
changed color to red-orange after the addition. After 3 h the
solution became deep orange. The solution was added to a solution
of NaBPh.sub.4 (250 mg, 0.658 mmol) in 1.5 mL of MeOH to cause the
formation of the precipitate. The orange-pink solid was filtered
and washed with 0.35 mL of MeOH three times and dried under vacuum.
Yield: 82% (0.33 mg); .sup.1H NMR (400 MHz, CD.sub.3CN) J: 1.36 (s,
6H, CH.sub.3CN), 4.10-4.25 (m, 4H, HCP), 4.10-4.25 (m, 4H, HC--N),
6.80-7.55 (m, 60H, ArH), 8.65-8.80 (m, 2H, HC.dbd.N). .sup.31P {H}
NMR (121 MHz; CD.sub.3CN): 74.01 ppm (s). Anal. Calcd for
C.sub.82H.sub.76N.sub.4P.sub.2FeB.sub.2: C, 78.38; H, 6.08; N,
4.46. Found: C, 77.58; H, 6.03; N, 4.26. MS (ESI+) Calcd. for
[C.sub.34H.sub.36N.sub.4P.sub.2Fe-2(CH.sub.3CN)].sup.2+: 268.2 m/z.
Found: 268.1 m/z. MS (ESI-) Calcd for [B(Ph).sub.4]-: 319.2 m/z.
Found: 319.2 m/z. The crystals were obtained by diffusion of
Et.sub.2O (1.0 mL) into the deep orange solution (1 mL) obtained as
above but before the addition of NaBPh.sub.4.
Example 9
Preparation of catalyst (vii):
[Fe(Ph.sub.2PCH.sub.2CH.dbd.NC.sub.2H.sub.4N.dbd.CHCH.sub.2PPh.sub.2)(CH.-
sub.3CN)(CO)](BPh.sub.4).sub.2
##STR00082##
[0263] The complex
[Fe(Ph.sub.2PCH.sub.2CH.dbd.NC.sub.2H.sub.4N.dbd.CH--CH.sub.2PPh.sub.2)(C-
H.sub.3CN).sub.2](BPh.sub.4).sub.2 (vi) (200 mg, 0.159 mmol) was
dissolved in (10 mL) of degassed acetone under inert atmosphere.
Resulting solution was placed in the CO high pressure reactor and
was stirred under 5 atmosphere of CO for 12 hours at room
temperature. Solvent was evaporated under reduced pressure and
resulting solid was washed with diethyl ether (5 mL) three times.
Yellow solid was dried under vacuum. Yield of (vii): 80% (158 mg);
.sup.1H NMR (400 MHz, acetone-d.sub.6) .delta.: 1.72 (s, 3H,
CH.sub.3CN), 3.95-4.50 (m, 4H, HC--N), 3.95-4.50 (m, 4H, HCP),
6.55-7.89 (m, 60H, ArH), 8.18-8.46 (m, 2H, HC.dbd.N); .sup.31P {H}
NMR (121 MHz; acetone-d.sub.6): 69.1 ppm (s).
Example 10
Preparation of trans-[Fe(MeCN).sub.2(6)](BF.sub.4).sub.2, wherein 6
is
##STR00083##
[0265] This ligand 6 was prepared as described in Jeffery, J. C.;
Rauchfuss, T. B.; Tucker, P. A. Inorg. Chem. 1980, 19, 3306-3316.
The complex trans-[Fe(MeCN).sub.2(6)](BF.sub.4).sub.2 was prepared
as follows. A suspension of 6 (149 mg, 0.25 mmol) in 5 mL of MeCN
was added to a solution of [Fe(H.sub.2O).sub.6][BF.sub.4].sub.2 (84
mg, 0.25 mmol) in MeCN (10 mL). After stirring for 1 h, the red
solution was concentrated to 1 mL and 10 mL of Et.sub.2O was added.
A purple powder precipitated. The powder was isolated and washed
with hexane. (200 mg, 87%). Crystals suitable for X-ray diffraction
studies were obtained from a MeCN/Et.sub.2O solution. .sup.1H NMR
(400 MHz, CDCl.sub.3): 9.46 (s, CH.dbd.N), 8.07-6.71 (m, ArH), 4.35
(s, CH.sub.2), 2.00 (s, CH.sub.3CN); .sup.31P{.sup.1H} NMR (161
MHz, CDCl.sub.3) 54.4 (s). Anal. Calcd for
C.sub.44H.sub.40N.sub.4B.sub.2F.sub.8P.sub.2Fe: C, 57.68; H, 4.40;
N, 6.12%. Found: C, 57.16; H, 4.40; N, 5.86%.
Example 11
Preparation of catalyst (viii): trans-[Fe(MeCN)(CO)
(6)](BF.sub.4).sub.2
##STR00084##
[0267] Complex trans-[Fe(MeCN).sub.2(6)](BF.sub.4).sub.2 was
reacted with CO (2 atm) in acetone at room temperature to produce
complex (viii). Yield: 1.14 g (1.3 mmol, 87%.). 1H NMR (d3-MeCN,
300 MHz): 1H NMR 4.01 (br s, 4H, CH2), 7.20-7.98 (several m, 20H,
Ph), 9.21 (br s, 2H, CH.dbd.N). 31P NMR (CD2Cl2, 121 MHz): 50.8
(s). Anal. Calcd. for C43H37B2F8N3P2Fe1: C, 57.18; H, 4.13; N,
4.65. Found: C, 56.12; H, 4.15; N, 4.83.
Example 12
Preparation of complex:
trans-(R,R)-[Fe(MeCN).sub.2(PPh.sub.2CH.sub.2CHNC.sub.6H.sub.10NCHCH.sub.-
2PPh.sub.2)](BF.sub.4).sub.2
##STR00085##
[0269] The diphenylphosphino-acetaldehyde hydrobromide dimer from
Example 1 (200 mg, 0.324 mmol) was completely dissolved in MeOH (6
mL). [Fe(H.sub.2O).sub.6][BF.sub.4].sub.2 (164 mg, 0.485 mmol) was
added to the reaction mixture. NaOMe (34.9 mg, 0.647 mmol) was
added as a MeOH (1 mL) solution and the color of the solution
changed from colorless to clear yellow. After 10 min of stirring, 1
mL of acetonitrile was added to give precursor solution B.
[0270] (1R,2R)-(-)-1,2-diaminocyclohexane (37 mg, 0.32 mmol) was
dissolved in 0.5 mL of acetonitrile and was added to the precursor
solution over the course of 20 min. The solution changed color to
purple after addition. The resulting solution was heated at
40.degree. C. for 20 h to give a deep orange solution. The solvent
volume was reduced by one half and the resulting solution was added
to a solution of NaBPh.sub.4 (250 mg, 0.658 mmol) in 1.5 mL of MeOH
to cause the formation of a precipitate. An orange-red solid was
recovered by filtration and washed with 0.15 mL of MeOH three times
and dried with vacuum. Yield: 54% (0.23 mg); .sup.1H NMR (400 MHz,
CD.sub.3CN) .delta.: 1.33 (s, 6H, CH.sub.3CN), 1.29-1.39 (m, 2H, H
of C.sub.6H.sub.10), 1.68-1.76 (m, 2H, H of C.sub.6H.sub.10),
1.98-2.28 (m, 2H, H of C.sub.6H.sub.10), 2.70-2.78 (m, 2H, H of
C.sub.6H.sub.10), 3.54-3.58 (m, 2H, HC--N), 3.88-4.01 (m, 2H, HCP),
4.34-4.49 (m, 2H, HCP), 6.8-7.5 (m, 60H, ArH), 8.60-8.74 (m, 2H,
HC.dbd.N). .sup.31P {H} NMR (121 MHz; CD.sub.3CN): 73.96 ppm (s).
Anal. Calcd for C.sub.86H.sub.82N.sub.4P.sub.2FeB.sub.2: C, 78.78;
H, 6.31; N, 4.27. Found: C, 77.00; H, 5.99; N, 4.34. MS (ESI.sup.+)
Calcd for [C.sub.38H.sub.42N.sub.4P.sub.2Fe-2(CH.sub.3CN)].sup.2+:
268.1 m/z. Found: 268.1 m/z. MS (ESI.sup.-) Calcd for
[B(Ph).sub.4].sup.-: 319.2 m/z. Found: 319.2 m/z.
Example 13
Preparation of
trans-(R,R)--[Fe(CO)(NCMe)(PPh.sub.2CH.sub.2CHNC.sub.6H.sub.10NCHCH.sub.2-
PPh.sub.2)](BF.sub.4).sub.2
##STR00086##
[0272] The complex was prepared according to the method of example
9. .sup.31P NMR(.sup.1H) d (66.78, 67.05) and d(70.52, 70.79) J=81
Hz.
Example 14
Preparation of complex:
trans-[Fe(MeCN).sub.2(PPh.sub.2CH.sub.2CHNC.sub.6H.sub.4NCHCH.sub.2PPh.su-
b.2)](BF.sub.4).sub.2
##STR00087##
[0274] Ortho-phenylenediamine (35 mg, 0.32 mmol) was dissolved in
0.5 mL of acetonitrile and was added to the precursor solution (A)
of Example 8 over the course of 20 minutes at 22.degree. C. The
solution changed color to orange after the addition. The resulting
residue was added to the solution of NaBPh.sub.4 (250 mg, 0.658
mmol) in 1 mL of MeOH to cause the formation of the precipitate.
The red-orange solid was isolated by filtration and washed with
0.15 mL of MeOH three times and dried under vacuum. Yield: 86%
(0.36 mg); .sup.1H NMR (400 MHz, CD.sub.3CN) .delta.: 2.10 (s, 6H,
CH.sub.3CN), 4.52-4.60 (m, 4H, HCP), 6.80-8.20 (m, 64H, HAr),
9.32-9.44 (m, 2H, HC.dbd.N). .sup.31P {H} NMR (121 MHz;
CD.sub.3CN): 68.33 ppm (s). Anal. Calcd for
C.sub.38H.sub.36N.sub.4P.sub.2FeB.sub.2: C, 79.19; H, 5.87; N,
4.29. Found: C, 76.83; H, 5.80; N, 4.15. MS (ESI.sup.+) Calcd for
[C.sub.86H.sub.76N.sub.4P.sub.2Fe-2(CH.sub.3CN)].sup.2+: 292.2 m/z.
Found: 292.1 m/z. MS (ESI.sup.-) Calcd for [B(Ph).sub.4].sup.-:
319.2 m/z. Found: 319.2 m/z.
Example 15
Preparation of the dicyclohexylphosphino-acetaldehyde hydrobromide
dimer
##STR00088##
[0276] A Schlenk flask was charged with dicyclohexylphosphine (2.53
g, 0.013 mol) and dry THF (10 mL). Bromoacetaldehyde diethyl acetal
(2.50 g, 0.013 mol) was added over the course of 15 min. The
mixture was stirred for 1 hour, at which time a white precipitate
was evident. An excess amount of degassed water (1 mL) was added
and the mixture was allowed to reflux overnight to yield a pristine
white sludge. The solid was collected by filtration under air and
washed with water (2.times.3 mL) and diethyl ether (2.times.3 mL).
Drying in vacuo yielded the phosphonium dimer as an air-stable
white powder. Yield: 3.25 g (80%); .sup.1H NMR (400 MHz,
CD.sub.3CN) .delta.: 1.42-2.19 (m, HCy), 2.80 (q), 3.08 (m), 5.39
(dd, J.sub.HP=26 Hz, J.sub.HH=4 Hz), 5.23 (dd, J.sub.HP=22 Hz,
J.sub.HH=4 Hz). .sup.31P {.sup.1H} NMR (121 MHz; CD.sub.3CN)
.delta.: 27.2 (s), 28.1 (s). Anal. Calcd for
C.sub.28H.sub.52O.sub.2P.sub.2Br.sub.2: C, 52.35; H, 8.16. Found:
C, 51.93; H, 8.46. MS (ESI, methanol/water; m/z.sup.+): 241.2
[C.sub.28H.sub.52O.sub.2P.sub.2].sup.2+.
Example 16
Preparation of complex:
[Fe(Cy.sub.2PCH.sub.2CH.dbd.NC.sub.2H.sub.4N.dbd.CHCH.sub.2PCy.sub.2)(CH.-
sub.3CN).sub.2](BPh.sub.4).sub.2]
##STR00089##
[0278] A vial was charged with the
dicyclohexylphosphino-acetaldehyde hydrobromide dimer (200 mg,
0.311 mmol), KOtBu (70 mg, 0.623 mmol) and CH.sub.3CN (4 mL). After
stirring for 5 minutes, [Fe(H.sub.2O).sub.6][BF.sub.4].sub.2 (158
mg, 0.467 mmol) in CH.sub.3CN (2 mL) was added to the white slurry.
The solution turned grey-yellow after 5 minutes; ethylenediamine
(0.34 mL from a stock solution of 200 mg in 4 mL CH.sub.3CN) was
added. The mixture turned pink immediately. After the reaction has
gone to completion overnight, the mixture was filtered through a
pad of Celite to remove a grey-white precipitate. Solvent was
removed under reduced pressure to give a red-pink residue. The
solid was dissolved in MeOH (2 mL) and added to a solution of
NaBPh.sub.4 (234 mg, 0.685 mmol) in MeOH (1 mL) to cause
precipitation of a pale pink solid. The solid was filtered and
washed with MeOH (2.times.1 mL) and dried under vacuum. Yield: 80%
(319 mg). Single crystals suitable for an X-ray diffaction study
were obtained by slow diffusion of pentane into
CH.sub.3CN/CH.sub.2Cl.sub.2 (1:1 by volume) at -40.degree. C.
.sup.1H NMR (400 MHz, CD.sub.3CN) .delta.: 1.11-1.95 (m, HCy,
CH.sub.3), 3.31 (d, 4H, H.sub.2CP), 3.95 (s, 4H, H.sub.2C--N),
6.8-7.3 (m, HAr), 8.41 (m, 2H, HC.dbd.N). .sup.13C {.sup.1H} NMR
(100 MHz, CD.sub.3CN) .delta.: 26.58 (C.sub.Cy), 27.63 (t,
J.sub.CP=5.1 Hz, C.sub.Cy), 27.82 (t, J.sub.CP=5.1 Hz, C.sub.Cy),
29.87 (C.sub.Cy), 30.04 (C.sub.Cy), 35.72 (t, J.sub.CP=6.9 Hz,
C.sub.CyP), 36.92 (dd, J.sub.CP=15, 10 Hz, CH.sub.2P), 61.10
(CH.sub.2N), 122.61 (C.sub.PhB), 126.43 (q, J.sub.CB=2.7 Hz,
C.sub.PhB), 136.58 (q, J.sub.CB=1.4 Hz, C.sub.PhB), 164.62 (m,
J.sub.CB=49 Hz, C.sub.PhB), 177.86 (HC.dbd.N). .sup.31P
{.sup.1H}NMR (161 MHz, CD.sub.3CN) .delta.: 68.5 (s). Anal. Calcd
for C.sub.82H.sub.100N.sub.4P.sub.2FeB.sub.2: C, 76.88; H, 7.87; N,
4.37. Found: C, 71.23; H, 7.51; N, 4.47. MS (ESI, methanol/water;
m/z.sup.+): 505.4
[C.sub.30H.sub.55N.sub.2P.sub.2--(Fe(NCCH.sub.3).sub.2)].sup.+.
Example 17
Preparation of catalyst precursor:
[Fe(Cy.sub.2PCH.sub.2CH.dbd.NC.sub.2H.sub.4N.dbd.CHCH.sub.2PCy.sub.2)(Br)-
(CO)][BPh.sub.4]
##STR00090##
[0280] A vial was charged with the
dicyclohexylphosphino-acetaldehyde hydrobromide dimer (200 mg,
0.311 mmol), KOtBu (70 mg, 0.623 mmol) and CH.sub.3CN (4 mL). After
stirring for 5 minutes, [Fe(H.sub.2O).sub.6][BF.sub.4].sub.2 (158
mg, 0.467 mmol) in CH.sub.3CN (2 mL) was added to the white slurry.
The solution turned grey-yellow after 5 minutes; ethylenediamine
(0.34 mL from a stock solution of 200 mg in 4 mL CH.sub.3CN) was
added. The mixture turned pink immediately. After the reaction has
gone to completion overnight, the mixture was filtered through a
pad of Celite to remove a grey-white precipitate and then
transferred to a Shlenk flask. Solvent was removed under reduced
pressure to give a red-pink residue. Acetone (15 mL) was added and
the solution was stirred under constant flow of CO overnight. The
resulting yellow-brown solution was evaporated to dryness,
dissolved in MeOH (2 mL) and added to a solution of NaBPh.sub.4 (94
mg, 0.274 mmol) in 1 mL of MeOH to cause formation of a yellow
precipitate. Yield: 63% (150 mg). Single crystals suitable for an
X-ray diffaction study were obtained by slow diffusion of hexanes
into THF. .sup.1H NMR (400 MHz, CD.sub.2Cl.sub.2) .delta.:
1.20-1.39 (m, HCy), 2.50 (br. m, 2H, HCyP) 2.86 (dd, J.sub.HP=19.0
Hz, 2H, HCP), 3.27 (dd, J.sub.HP=20.0 Hz, 2H, HCP), 3.44 (m,
J.sub.HH=6.2 Hz, 2H, HCN), 3.81 (m, J.sub.HH=5.6 Hz, 2H, HCN),
6.88-7.39 (m, HAr), 7.49 (m, 2H, HC.dbd.N). .sup.13C {.sup.1H} NMR
(100 MHz, CD.sub.2Cl.sub.2) .delta.: 26.34 (d), 27.80 (m), 29.47
(t), 30.24, 30.75 (d), 38.29 (q), 39.73 (dd), 60.93, 105.35,
122.65, 126.52, 136.71, 164.01-165.68 (m, J.sub.C-B 49 Hz), 174.42.
.sup.31P {.sup.1H} NMR (161 MHz, CD.sub.2Cl.sub.2): 69.78 ppm. IR
(KBr) 1948 cm.sup.-1 (.sub.C.ident.O) Anal. Calcd for
C.sub.55H.sub.74BBrFeN.sub.2OP.sub.2: C, 66.88; H, 7.55; N, 2.84.
Found: C, 65.30; H, 7.89; N, 3.15.
Example 18
Preparation of the di(p-tolyl)phosphino-acetaldehyde hydrobromide
dimer
##STR00091##
[0281] meso- and rac-
[0282] A Schlenk flask was charged with KH (0.524 g, 13.1 mmol),
and dry THF (13 mL). Di(p-tolyl)phosphine (2.331 g, 10.9 mmol) was
added, and the solution turned red in colour. The solution was
stirred for 30 min, and then cooled to -78.degree. C.
Bromoacetadehyde diethyl acetate (1.68 mL, 10.9 mmol) was added
over 20 min, and the solution turned yellow. The solution was
warmed to room temperature and 48% HBr (2.5 g, 14.8 mmol) was
added. A white precipitate formed, and the solution turned
colourless. The mixture was heated at 45.degree. C. for 2 hours,
and then left in the freezer overnight. The precipitate was
filtered off and washed with 15 mL cold H.sub.2O, as well as 15 mL
of a 1:1 mixture of cyclohexanol:ethyl acetate. The precipitate was
then recrystallized in MeOH and ether, and dried under high vacuum.
Yield: 2.698 g, 87.8%. Diastereomer 1: 1H NMR (CD.sub.3OD, 400 MHz,
6): 8.06 (dd, J=8.2, 12.3, aromatic CH, 4H), 7.63-7.58 (m, aromatic
CH, 8H), 7.48 (dd, J=2.5, 8.2, aromatic CH, 4H), 6.19 (dd, J=6.8,
21.5, PCH(OH), 2H), 4.37-4.15 (m, H1 of PCH(OH)CH.sub.2, 2H),
3.99-3.81 (m, H2 of PCH(OH)CH.sub.2, 2H), 2.53 (s, CH3, 6H), 2.44
(s, CH3, 6H). .sup.31P NMR (CD.sub.3OD, 400 MHz, 6): 11.12.
.sup.13C NMR (CD.sub.3OD, 400 MHz, 6): 146.8 (aromatic C--P), 146.7
(aromatic C--P), 133.7 (aromatic CH), 133.1 (aromatic CH), 130.6
(aromatic CH), 130.4 (aromatic CH), 113.9 (CH.sub.3C), 113.0
(CH.sub.3C), 61.1 (PCHOH), 22.1 (PCH.sub.2), 20.5 (CH.sub.3), 20.3
(CH.sub.3). Diastereomer 2: 1H NMR (CD.sub.3OD, 400 MHz, 6): 7.96
(dd, J=8.3, 12.5, aromatic CH, 4H), 7.86 (dd, J=8.3, 12.0, aromatic
CH, 4H), 7.63-7.58 (m, aromatic CH, 4H), 7.56 (dd, J=3.2, 8.3,
aromatic CH, 4H), 5.80 (ddd, J=2.5, 9.4, 16.3, PCH(OH), 2H),
4.37-4.15 (m, H1 of PCH(OH)CH.sub.2, 2H), 3.99-3.81 (m, H2 of
PCH(OH)CH.sub.2, 2H), 2.50 (s, CH3, 6H), 2.49 (s, CH3, 6H).
.sup.31P NMR (CD.sub.3OD, 400 MHz, 6): 16.06. .sup.13C NMR (CD3OD,
400 MHz, .delta.): 147.5 (aromatic C--P), 146.9 (aromatic C--P),
133.3 (aromatic CH), 132.9 (aromatic CH), 131.3 (aromatic CH),
130.5 (aromatic CH), 112.5 (CH.sub.3C), 111.7 (CH.sup.3C), 62.2
(PCHOH), 23.6 (PCH.sub.2), 20.4 (CH3). Anal. Calcd for
[C.sub.32H.sub.36P.sub.2O.sub.2][Br].sub.2[CH.sub.3OH][H.sub.2O]:
C, 54.71; H, 5.84. Found: C, 54.65; H, 6.04. MS (ESI,
methanol/water; m/z+): 257.1
[C.sub.32H.sub.36O.sub.2P.sub.2].sup.2+. The diastereomeric excess
was found to be 13%, as determined by .sup.1H NMR, and .sup.31P
NMR.
Example 19
Preparation of catalyst precursor:
[Fe((C.sub.7H.sub.7).sub.2PCH.sub.2CH.dbd.NCHPhCHPhN.dbd.CHCH.sub.2P(C.su-
b.7H-.sub.7)(CH.sub.3CN).sub.2](BPh.sub.4).sub.2]
##STR00092##
[0284] A vial was charged with the
di(p-tolyl)phosphino-acetaldehyde hydrobromide dimer (235 mg, 0.324
mmol), and CH.sub.3CN (4 mL). A yellow solution of
[Fe(H.sub.2O).sub.6][BF.sub.4].sub.2 (164 mg, 0.485 mmol) in
CH.sub.3CN (2 mL) was added to the white slurry, followed by NaOMe
(34.9 mg, 0.647 mmol) in MeOH (1 mL). The color of the solution
changed from yellow to colourless. After 20 min of stirring
(1R,2R)-(+)-1,2-diphenylethylenediamine (69 mg, 0.323 mmol) in 0.5
mL of acetonitrile was added over 5 min, and
[0285] the solution turned deep purple. After 48 h the mixture was
filtered to remove a white precipitate. The solvent was removed
under reduced pressure to give a red-pink residue. The residue was
dissolved in MeOH (2 mL) and added to a solution of NaBPh.sub.4
(250 mg, 0.658 mmol) in MeOH (1 mL) to cause precipitation of a
pale pink solid. The product was filtered and washed with MeOH
(2.times.5 mL) and dried under vacuum. Yield: 26.3% (120 mg).
Crystals suitable for X-ray diffraction studies were obtained by
slow diffusion of Et.sub.2O into CH.sub.3CN/MeOH (1:5 by volume).
.sup.1H NMR (400 MHz, CD.sub.3CN) .delta.: 2.20 (s, 6H,
CH.sub.3CN), 3.90-4.03 (m, 2H, HCP), 4.15-4.30 (m, 2H, HCP), 5.42
(m, 2H, HC--N), 6.80-7.75 (m, 74H, aromatic H), 8.90-8.20 (m, 2H,
HC.dbd.N). .sup.31P {1H} NMR (121 MHz; CD3CN) .delta.: 70.52 ppm
(s). Anal. Calcd for [C.sub.98H.sub.92N.sub.4P.sub.2FeB.sub.2: C,
80.33; H, 6.33; N, 3.82. Found: C, 76.31; H, 6.71; N, 3.77. MS
(ESI, methanol/water; m/z+): 372.1
[C.sub.50H.sub.52N.sub.4P.sub.2Fe].sup.2+.
Example 20
##STR00093##
[0287] Following the same steps as in the synthesis of Example 19,
the reaction mixture that was stirred for 48 h was filtered and
transferred to a Schlenk flask. The solvent was removed under
pressure, and acetone (9 mL) was added. The solution was stirred
under a constant flow of CO overnight. The resulting yellow-brown
solution was evaporated to dryness, dissolved in MeOH (4 mL) and
added to a solution of NaBPh.sub.4 (125 mg, 0.329 mmol) in MeOH (1
mL) to cause formation of a yellow precipitate. Yield: 22.2% (108
mg). .sup.31P {.sup.1H} NMR (121 MHz; C.sub.6D.sub.6 insert)
.delta.: 65.96 (d, J=39.5 Hz), 67.93 ppm (d, J=39.5 Hz).
General procedure for Examples 21 and 22
[0288] In an Ar-filled glovebox diisopropylphosphine (for Example
21) or diethylphosphine (for Example 22) (15 mmol) was dissolved in
20 mL of dry THF. Bromoacetadehyde diethyl acetal (15 mmol) was
added to the resulting mixture on Ar line and resulting solution
was stirred for 4 h. The reaction was quenched with degassed
H.sub.2O (8 mL) and heated for over night at 45.degree. C. The
solvent was partially removed under vacuum and to give colorless
solution with white precipitate. The solution was stored for 3 h at
5.degree. C. The precipitate then was filtered and washed with
pre-cooled water (15 mL) and diethyl ether (10 mL) to give an
analytically pure sample. Crystals suitable for X-ray diffraction
experiments were obtained by slow diffusion of diethyl ether into a
saturated solution of Example 22 in methanol.
Example 21
##STR00094##
[0289] Properties of the di(i-propyl)phosphino-acetaldehyde
hydrobromide dimer
[0290] Yield: 2.93 g, 81%. The diastereomeric ratio was found to be
1:2, as determined by .sup.1H NMR. .sup.1H NMR (400 MHz,
CD.sub.3OD, resonances of two diastereomers overlap in region
.delta. 3.50-1.40; see below): .delta.5.60 (pseudo ddd,
.sup.3J.sub.HH=6.4 Hz, .sup.2J.sub.HP=22.3 Hz, 2H, CH(OH), major
diastereomer; .sup.31P{.sup.1H}, 5.60 (pseudo d, .sup.3J.sub.HH=6.5
Hz)), 5.44 (ddd, 1H, .sup.3J.sub.HH=3.0 Hz, .sup.3J.sub.HH=9.3 Hz,
.sup.2J.sub.HP=12.0 Hz, 2H, CH(OH), minor diastereomer;
.sup.1H{.sup.31P}, 5.44 (dd, .sup.3J.sub.HH=3.0 Hz,
.sup.3J.sub.HH=9.3 Hz)), 3.50-2.85 (m, overlap of 4H,
CH(OH)CH.sub.2P and 4H, (CH.sub.3).sub.2CHP (both diastereomers);
.sup.1H{.sup.31P}, same), 1.60-1.40 (m, 12H, (CH.sub.3).sub.2CHP,
(both diastereomers); .sup.1H{.sup.31P}, same). .sup.31P{.sup.1H}
NMR (161 MHz, CD.sub.3OD): .delta. 36.81 (s, minor diastereomer),
34.54 (s, major diastereomer). .sup.13C{.sup.1H} NMR (100 MHz,
CD.sub.3OD, signals of carbon atoms appear as a multiplets with
complex splitting patterns that arise from coupling to two
magnetically inequivalent phosphorus atoms in the structure):
.delta. 58.61 (m, CH(OH), minor diastereomer), 57.69 (m, CH(OH),
major diastereomer), 22.93 (m, CH.sub.2P, major diastereomer),
22.93 (m, CH.sub.2P, minor diastereomer), 21.23 (m, CH.sub.2P,
major diastereomer), 21.62 (d, .sup.2J.sub.CP=21.8 Hz,
C(CH.sub.3).sub.2P, minor diastereomer) 19.71 (d,
.sup.2J.sub.CP=40.5 Hz, C(CH.sub.3).sub.2P, major diastereomer),
16.45-15.35 (m, overlapping peaks of isopropyl methyl groups, both
diastereomers). Anal. Calcd for
C.sub.16H.sub.36P.sub.2O.sub.2Br.sub.2: C, 39.85; H, 7.52. Found:
C, 39.35; H, 7.32.
Example 22
##STR00095##
[0291] Properties of the di(ethyl)phosphino-acetaldehyde
hydrobromide dimer
[0292] Yield: 1.28 g, 40%. The diastereomeric ratio was found to be
1:2, as determined by .sup.1H NMR. .sup.1H NMR (400 MHz,
CD.sub.3OD, resonances of two diastereomers overlap; see below):
.delta.5.45-510 (m, 2H, CH(OH), diastereomers overlap;
.sup.1H{.sup.31P}, 5.36 (pseudo d, 2H, CH(OH), .sup.2J.sub.H-P=5.8
Hz, major diastereomer), 5.29 (pseudo dd, 2H, CH(OH),
.sup.3J.sub.H-H=3.4 Hz, .sup.2J.sub.H-P=9.2 Hz, minor
diastereomer)), 3.31-2.87 (m, 4H, CH(OH)CH.sub.2P, overlap of
diastereomers; .sup.1H{.sup.31P}, same), 2.58-2.08 (m, 8H,
(CH.sub.3CH.sub.2P, overlap of diastereomers; .sup.1H{.sup.31P};
same), 1.32-0.90 (m, 12H, CH.sub.3CH.sub.2P, overlap of
diastereomers; .sup.1H{.sup.31P}, same). .sup.31P{.sup.1H} NMR (161
MHz, CD.sub.3OD): .delta. 35.59 (s, minor diastereomer), 32.72 (s,
major diastereomer). .sup.13C{.sup.1H} NMR (100 MHz, CD.sub.3OD,
complex coupling of several carbon atoms results from coupling to
two magnetically unequivalent phosphorus atoms in the structure):
.delta.58.10 (m, CH(OH), minor diastereomer), 57.85 (m, CH(OH),
major diastereomer), 19.54 (m, CH.sub.2P, minor diastereomer),
18.35 (m, CH.sub.2P, major diastereomer), 12.50-9.12 (m,
CH.sub.3CH.sub.2P, overlap of diastereomer), 5.42-3.72 (m,
CH.sub.3CH.sub.2P, overlap of diastereomer). Anal. Calcd for
C.sub.12H.sub.28P.sub.2O.sub.2Br.sub.2: C, 33.82; H, 6.62. Found:
C, 33.92; H, 6.38.
[0293] While the present invention has been described with
reference to examples, it is to be understood that the invention is
not limited to the disclosed examples. To the contrary, the
invention is intended to cover various modifications and equivalent
arrangements included within the spirit and scope of the appended
claims.
[0294] All publications, patents and patent applications are herein
incorporated by reference in their entirety to the same extent as
if each individual publication, patent or patent application was
specifically and individually indicated to be incorporated by
reference in its entirety.
* * * * *