Highly enantioselective hydrogenation of simple ketones catalyzed by a Rh-PennPhos complex

Article abstract of DOI:10.1002/(sici)1521-3773(19980504)37:8<1100::aid-anie1100>3.0.co;2-3

Even alkyl methyl ketones undergo asymmetric hydrogenation with high enantioselectivity when a rhodium complex of the conformationally rigid chiral ligand 1 (Me-PennPhos; R = CH₃) is used as the catalyst. Basic additives such as 2,6-lutidine contribute to the achievement of high enantiomeric excesses.

Full text of DOI:10.1002/(sici)1521-3773(19980504)37:8<1100::aid-anie1100>3.0.co;2-3

COMMUNICATIONS
systems.[6] While systems for efficient transition metal cata-
lyzed asymmetric hydrogenation of functionalized ketones
have been realized,[7] highly enantioselective hydrogenation
of simple ketones that lack anchoring heteroatoms has not
been fully developed. Among the direct hydrogenation
catalytic systems,[8] promising results were achieved for
asymmetric hydrogenation of alkyl aryl ketones with a
mixture of a RuII ± BINAP complex (BINAP ˆ 2,2'-bis(diphe-
Highly Enantioselective Hydrogenation of
Simple Ketones Catalyzed by a Rh ± PennPhos
Complex**
Qiongzhong Jiang, Yutong Jiang, Dengming Xiao,
Ping Cao, and Xumu Zhang*
The development of new chiral ligands plays a crucial role
in expanding the utility of transition metal catalyzed asym-
metric reactions.[1] A major research goal in asymmetric
catalysis is to impart high enantioselectivity and activity to
important reactions by the invention of new chiral ligands and
the optimization of reaction conditions for use of these
ligands. Many effective chiral bisphosphanes contain a diaryl-
phosphane as the key steric group that defines the electronic
properties.[1] Recently, we designed conformationally rigid
endo-2,5-dialkyl-7-phosphabicyclo[2.2.1]heptanes as new chi-
ral scaffolds, and demonstrated that these monophosphane
species can be more effective for some asymmetric reactions[2]
than the conformationally flexible 2,5-disubstituted phospho-
lanes characteristic of the DuPhos and BPE ligands[3]
(Figure 1). Herein we report the synthesis of a novel class of
conformationally rigid chiral bisphosphanes, P,P'-1,2-phenyl-
enebis(endo-2,5-dialkyl-7-phosphabicyclo[2.2.1]heptanes
(PennPhos, 5 and 6).[4] Although PennPhos shares some
features with DuPhos, such as electron-donating properties
and a modular structure, it is bulkier, more rigid, and does not
form C2-symmetric compounds with many transition metals.
In addition, PennPhos can be made in large quantities from
inexpensive starting materials and is an air-stable solid.
nylphosphanyl)-1,1'-dinaphthyl),
a
chiral diamine, and
KOH.[8d] In this catalytic system, the chelating chiral diamine
is as important a stereochemistry-controlling element as the
chiral BINAP ligand. To date, simple metal complexes with
chiral bisphosphane ligands are ineffective for highly enan-
tioselective hydrogenation of simple ketones. Furthermore,
asymmetric reduction of simple dialkyl ketones generally
proceeds with low enantioselectivity in all reduction systems
with few exceptions.[5b, 5c] With a Rh ± PennPhos catalyst, we
have achieved unprecedented high enantioselectivity in
hydrogenation of both aryl alkyl and dialkyl ketones. This
success is based on the important finding that a weak base can
facilitate Rh-catalyzed hydrogenation of simple ketones; the
discovery itself may have fundamental significance for
organometallic chemistry.
The synthesis of PennPhos is illustrated in Scheme 1.
Enantiomerically pure cyclic 1,4-diols 1 and 2, which are
easily prepared by Haltermanꢁs procedure,[9] are converted
OMs
OH
R
R
R = Me, 3
R = iPr, 4
MsCl, Et3N
CH2Cl2
R = Me, 1
R = iPr , 2
R
R
> 99 %
R'
R
OMs
R
OH
PH2
P
R
DuPhos, BPE
P
R
, NaH
R'
R = Me, 5, 43 %
R = iPr, 6, 54%
PH2
R
R
P
P
Figure 1. Structural motifs of chiral 1,2-bis(phospholano)benzene (Du-
Phos) and 1,2-bis(phospholano)ethane (BPE) as well as rigid dialkyl-7-
phosphabicyclo[2.2.1]heptane.
HMPA, THF, 0 °C
20 °C
R
R
Scheme 1. Synthesis of the PennPhos ligands. HMPA ˆ hexamethyl phos-
phoramide, Ms ˆ methanesulfonyl.
We have directed much attention toward enantioselective
hydrogenation of simple ketones as a showcase for enantio-
selective transition metal catalyzed reactions with PennPhos.
Asymmetric hydrogenation is one of the most efficient
methods of making chiral alcohols, because transition metal
hydrogenation catalysts have potentially high catalytic activ-
ity compared to stoichiometric[5] and other catalytic reduction
into the corresponding mesylates 3 and 4 in high yields.
Nucleophilic substitution of the methanesulfonate groups
by 1,2-phenylenediphosphane[10] in the presence of
NaH generates the desired products P,P'-1,2-phenylene-
bis{(1R,2S,4R,5S)-2,5-dimethyl-7-phosphabicyclo[2.2.1]hep-
tane} (5, (R,S,R,S)-Me-PennPhos) and P,P'-1,2-phenylene-
bis[(1R,2R,4R,5R)-2,5-diisopropyl-7-phosphabicyclo[2.2.1]-
heptane} (6, (R,R,R,R)-iPr-PennPhos), respectively.
[*] Prof. Dr. X. Zhang, Dr. Q. Jiang, Y. Jiang, D. Xiao, P. Cao
Department of Chemistry, 152 Davey Laboratory
The Pennsylvania State University
Effective asymmetric hydrogenation of simple ketones
requires high intrinsic activity in the nonchiral form of the
reaction. Since simple ketones are typically poorer ligands
than are olefins, many Rh ± phosphane complexes show no
activity for the hydrogenation of simple ketones. An impor-
University Park, PA 16802 (USA)
Fax: (‡1)814-863-8403
E-mail: xumu@chem.psu.edu
[**] This work was supported by a Camille and Henry Dreyfus New
Faculty Award, an ONR Young Investigator Award, and a DuPont
Young Faculty Award as well as by DuPont Agrochemical, Amoco,
and Hoechst Celanese Corporation. We acknowledge a generous loan
of precious metals from Johnson Matthey Inc. We thank Supelco for a
gift of a b-DEX GC column and Professor Tim Glass for helpful
‡
tant finding by Osborn and Schrock is that [RhH2L2X2]
(L ˆ electron-donating phosphanes such as PPh2Me or
PMe3, X ˆ solvent) is a reasonable catalyst for the hydro-
genation of simple ketones in the presence of a small amount
of water.[11] Since PennPhos ligands are more electron rich
suggestions.
phosphabicyclo[2.2.1]heptane)
PennPhos ˆ P,P'-1,2-phenylenebis(endo-2,5-dialkyl-7-
1100
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1433-7851/98/3708-1100 $ 17.50+.50/0
Angew. Chem. Int. Ed. 1998, 37, No. 8

COMMUNICATIONS
than triarylphosphanes, we anticipated that they might show
good activity towards asymmetric hydrogenation of simple
ketones.
Table 1 outlines the results of asymmetric hydrogenation
according to Equation (a) with acetophenone as a typical
enantioselectivity and the rate of the reaction over the entire
concentration range (0.1 ± 1 equiv, entry 4). With Et3N as the
additive (entry 5), higher conversion and better enantioselec-
tivity were observed when less than 0.2 equivalents of base
were present in the catalytic system. Use of more than
0.3 equivalents of Et3N caused a decrease in reactivity and
enantioselectivity. The reaction gave the opposite configura-
tion with low conversion when one equivalent of Et3N was
used. Hydrogenation in the presence of 2-methylimidazole
(entry 6) also showed initial enhancement and then erosion of
both the reactivity and selectivity. In contrast, both enantio-
selectivity and conversion were increased when 0.1 to 1
equivalent of 2,6-lutidine was used (entry 7). Up to 95% ee
was observed for the hydrogenation of acetophenone. This is
the highest enantioselectivity achieved with a direct hydro-
genation catalyst of a Group 8 transition metal (87% ee was
obtained with Noyoriꢁs Ru system[8d]). Therefore, bromide
and 2,6-lutidine are useful promoters for the Rh-catalyzed
enantioselective hydrogenation of acetophenone.
The mechanism of this Rh-catalyzed asymmetric hydro-
genation is not well understood at present. Based on the
commonly accepted mechanism,[12] we offer the following
rationale to explain our observations (Scheme 2): Addition of
5 to [Rh(cod)Cl]2 in MeOH generates [Rh(cod)(5)]Cl.[13] This
catalytic precursor can be hydrogenated to give the RhI
intermediate 7. Oxidative addition of hydrogen to 7 produces
the six-coordinate RhIII species 8, which is converted into 9 by
ligand substitution. Insertion of the ketone into the Rh H
bond forms the RhIII ± alkoxyl complex 10, in which the
remaining hydride is located trans relative to the alkoxide
group. Therefore, the reductive elimination of 10 to regener-
ate 7 is difficult under normal conditions. The major function
of the added bases may be to deprotonate 10, while the
conjugate acid can protonate the alkoxide ligand. A similar
push ± pull mechanism was suggested by Osborn and Schrock
for the Rh-catalyzed hydrogenation of simple ketones pro-
moted by small quantities of water.[11] With a 1:1 ratio of
Rh:additives, a variety of Rh derivatives can be generated.
For example, halide and alkoxide may displace the chloride in
8 to form 11, which can lead to a Rh dimer or other
unproductive species. With strongly coordinating ligands such
as an imidazole, irreversible formation of coordinately
O
OH
(S)
[Rh(cod)Cl]2, 5
+ H2
(a)
additive, MeOH, 24 h, 20 °C
Table 1. Rh-catalyzed asymmetric hydrogenation of acetophenone
according to Equation (a).[a]
Entry Additive
Conversion[%](ee[%]) for the following ratios of
additive:Rh catalyst
0.15 0.2 0.3
0.0
0.1
1.0
1
2
3
4
5
6
7
NaOMe
LiOtBu
LiCl
KBr
Et3N
45(57) 56(70) 69(83) 71(88) 41(80) 25(15R)
80(91) 58(89) 19(78) 20(23R)
49(66)
74(80)
46(70) 47(72) 44(67)
82(88) 85(89) 89(92)
89(90) 78(92) 28(82) 18(4R)
94(94) 79(92) 12(1)
2-Me-imidazole
2,6-lutidine
86(87)
72(83) 84(90) 94(94) 97(95) 93(95)
[a] Reaction conditions: room temperature, 30 atm of H2, 24 h, 1.0 mmol of
substrate, 0.1m, substrate:[Rh(cod)Cl]2:5 ˆ 1:0.005:0.01. See Experimental
Section for further details.
substrate and the Rh complex of 5 as the catalyst. Initially,
extensive screening of catalytic conditions showed that the
asymmetric hydrogenation gave good enantioselectivity and
activity when [Rh(cod)Cl]2 was used as the precursor under
30 atm of H2 in MeOH. The Rh complex of 6 is a less effective
catalyst than the Rh complex of 5. Unlike the hydrogenation
system of Osborn and Schrock, addition of a small amount of
water had no effect on the catalytic activity. However, we
found a dramatic effect with other additives. Not only does the
enantioselectivity strongly depend on the additive used, but
catalytic activity also varies to a great extent.
Three classes of additives were screened in the catalytic
system: ionic bases (Table 1, entries 1, 2), halides (en-
tries 3, 4), and neutral bases (entries 5 ± 7). In the absence of
additives, asymmetric hydrogenation of aceto-
phenone catalyzed by the Rh complex of 5 was
sluggish and gave the secondary alcohol with only
57% ee (entry 1). In the presence of catalytic
amounts of additives (0.1 ± 0.2 equiv based on
Rh), both reactivity and enantioselectivity were
increased.
H
H
H2
X–
P
X
P
P
Cl
H
P
Cl
S
Rh
S
Rh
S
Rh
H
P
P
7
11
8
H
B
OH
O
S
P
Cl
H
Rh
B
Different effects were observed depending on
P
B or X–
the type and amount of additives used. For the
12
RO– or B
ionic bases (entries 1, 2), addition of one equiv-
alent of base slowed down the reaction and
surprisingly gave the chiral alcohol with the
opposite configuration. The halide effect was
studied with two different salts. The presence of
excess chloride showed little effect on the catalyst
activity and selectivity (entry 3). However, the
addition of bromide could enhance both the
H
H
H
Cl
S
P
P
P
P
H2
P
Cl
H
H
H
Rh
Rh
Rh
O
Rh
S
P
P
S
P
H
O
14
13
S
ROH, S or BH+
9
10
Scheme 2. Proposed mechanism for Rh-catalyzed asymmetric hydrogenation. S ˆ MeOH,
B ˆ neutral base, X ˆ halogen, OR.
Angew. Chem. Int. Ed. 1998, 37, No. 8
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1433-7851/98/3708-1101 $ 17.50+.50/0
1101

COMMUNICATIONS
saturated species 12 is possible. Replacing these ligands by
simple ketones is difficult, and low catalytic activity is
expected. In the presence of strong bases such as alkoxide
or Et3N, reductive elimination of HCl from 8 will form the
RhI ± hydrido species 13, which may lead to the opposite
enantiomer by a competitive pathway.[11] Clearly, the enan-
tioselectivity of the reaction is a useful probe for under-
standing the reaction mechanism of the Rh-catalyzed hydro-
genation. Oxidative addition of H2 to 13 is likely to be slow, as
14 has two hydrido ligands located trans to phosphane ligands.
On the other hand, substitution of chloride by bromide
changes the electronic nature of the Rh complex, and may
generate more active catalysts for the hydrogenation of
ketones. Use of noncoordinating and weaker bases such as
2,6-lutidine could accelerate the reductive elimination of 10
without unwanted formation of 12 and 13.
Based on the observation that bromide and 2, 6-lutidine are
important promoters for the hydrogenation of simple ketones,
we examined the asymmetric hydrogenation of various simple
ketones with the Rh complex of 5 as the catalyst [Eq. (b),
Table 2]. Two sets of reaction conditions were applied to
achieve high enantioselectivity: 1) use of 0.4 equivalents of
2,6-lutidine (based on Rh) or 2) use of 0.8 equivalents of 2,6-
lutidine and 1 equivalent of KBr (based on Rh). For most aryl
methyl ketones (Table 2, entries 1 ± 8), high enantioselectiv-
ities (93 ± 96% ee) were observed. The presence of both 2,6-
lutidine and KBr accelerated the reaction and enhanced the
enantioselectivity (entries 4/3 and 6/5). These conditions were
then used for the hydrogenation of other ketones. Increasing
the bulk of the alkyl group by going from methyl to ethyl or
isopropryl in the alkyl aryl ketone dramatically decreased the
reactivity and enantioselectivity (entries 1/5 and 6/7). This
clearly indicates that the chiral environment around the Rh
complex of 5 can effectively discriminate between methyl and
other alkyl groups. To test this speculation, we carried out
asymmetric hydrogenations of several alkyl methyl ketonesÐ
the toughest problem for asymmetric reduction (entries 9 ±
14). Enantiomeric excesses of up to 94% ee for tert-butyl
methyl ketone (entry 14) and 92% ee for cyclohexyl methyl
ketone (entry 13) were observed. The enantioselectivity
decreased with smaller alkyl groups. With isopropyl methyl
ketone and isobutyl methyl ketone, 84% ee (entry 12) and
85% ee (entry 11) were achieved respectively. However, even
with unbranched alkyl groups, good enantioselectivities of
73% ee (entry 9) and 75% ee (entry 10) were still achieved.
To the best of our knowledge, our results of asymmetric
hydrogenation of alkyl aryl ketones by the Rh complex of 5
are comparable to or better than those with other hydro-
genation catalysts, and our hydrogenation results of alkyl
methyl ketones with this system gives the highest enantiose-
lectivity reported to date.
OH
O
[Rh(cod)Cl]2, 5
+
H2
(b)
(S)
2,6-lutidine, MeOH
R
R'
R
R'
Table 2. Asymmetric hydrogenation of simple ketones catalyzed by a
Rh ± PennPhos complex according to Equation (b).[a]
Entry Ketone
Equiv of Equiv Time[h] Yield[%] ee[%]
lutidine[b] of KBr
O
1
2
3
0.4
0.4
0.8
0.8
0.8
±
±
24
53
97
94
56
83
71
95
95
91
94
89
O
±
108
48
O
H3CO
4
1.0
±
5
108
O
6
7
0.8
0.8
1.0
1.0
88
94
95
20
93
72
O
O
8
0.8
1.0
100
99
96
O
O
9
0.8
0.8
0.8
0.8
0.8
0.8
1.0
1.0
1.0
1.0
1.0
1.0
56
48
99
96
66
99
90
51
73
75
85
84
92
94
O
10
11
12
13
14
O
75
O
94
O
106
96
O
[a] Reaction conditions: room temperature, 30 atm of H2, 0.5 mmol of
substrate, 0.125m, substrate:[Rh(cod)Cl]2:5 ˆ 1:0.005:0.01]. See Experi-
mental Section for further details. Long reaction time was used to achieve
the maxium conversion; for many substrates the reaction may be complete
within a much shorter time. [b] Based on Rh.
ligand should lead to practical asymmetric hydrogenation
catalysts for simple ketones.
Experimental Section
In summary, we have synthesized new conformationally
rigid bisphosphanes, the PennPhos ligands. For the asymmet-
ric hydrogenation of ketones catalyzed by Rh complexes of
these ligands, remarkable additive effects and high enantio-
selectivies for both alkyl aryl and alkyl methyl ketones are
found. Continuing research will focus on understanding the
reaction mechanism and enhancing the reaction rate. Fine-
tuning the steric and electronic environment of the PennPhos
Compounds 1 ± 4[9] and 1,2-phenylenediphosphane[10] were made according
to literature procedures. MeOH was distilled from Mg/Na over a long
column under N2. All the operations were carried out under a N2
atmosphere.
1
5: H NMR (CDCl3): d ˆ 7.25 ± 7.10 (m, 2H, aromatic), 7.08 ± 6.95 (m, 2H,
aromatic), 3.21 (br d, 2H, 2J(P,H) ˆ 14.5 Hz, PCH), 2.58 (br d, 2H,
2J(P,H) ˆ 13.4 Hz, PCH), 1.90 ± 1.60 (m, 12H), 1.55 ± 1.35 (m, 2H), 1.17
(d, 6H, 3J(H,H) ˆ 6.3 Hz, CH3), 0.60 (d, 6H, 3J(H,H) ˆ 6.3 Hz, CH3); 13C
1102
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1433-7851/98/3708-1102 $ 17.50+.50/0
Angew. Chem. Int. Ed. 1998, 37, No. 8

COMMUNICATIONS
NMR (CDCl3): d ˆ 143.94, 143.66, 143.48, 143.20, 131.05, 131.00, 130.93,
126.33, 46.24, 46.20, 46.17, 46.13, 45.92, 45.69, 45.61, 45.38, 40.17, 40.05,
39.89, 39.73, 39.61, 39.52, 39.33, 39.29, 39.26, 34.76, 34.61. 34.51, 34.41, 34.26,
22.69, 22.65, 22.61, 20.82; 31P NMR (CDCl3): d ˆ 7.3; [a]D ˆ ‡221.88 (c ˆ
1.01, CHCl3); HR-MS calcd for C22H32P2: 358.1975; found: 358.1982.
Mol. Catal. 1989, 29, 165; c) X. Zhang, T. Taktomi, T. Yoshizumi, H.
Kumobayashi, S. Akutagawa, K. Mashima, H. Takaya, J. Am. Chem.
Soc. 1993, 115, 3318; d) T. Ohkuma, H. Ooka, S. Hashiguchi, T.
Ikariya, R. Noyori, ibid. 1995, 117, 2675.
[9] a) Z. Chen, R. L. Halterman, Synlett 1990, 103; b) Z. Chen, K. Eriks,
R. L. Halterman, Organometallics 1991, 10, 3449.
1
6: H NMR (CDCl3): d ˆ 7.20 ± 7.10 (m, 2H, aromatic), 7.05 ± 6.90 (m, 2H,
[10] E. P. Kyba, S.-T. Liu, R. L. Harris, Organometallics 1983, 2, 1877.
[11] R. R. Schrock, J. A. Osborn, J. Chem. Soc. Chem. Commun. 1970, 567.
[12] J. P. Collman, L. S. Hegedus, J. R. Norton, R. G. Finke, Principles and
Applications of Organotransition Metal Chemsitry, University Science
Books, Mill Valley, 1987, chap. 10.
[13] 31P NMR data for [Rh(cod)5]Cl (prepared in situ, CD3OD): ABX
system, d ˆ 50.7 (dd, 1J(Rh,P) ˆ 140.6 Hz), 2J(P,P) ˆ 23.6 Hz), 37.1
(dd, 1J(Rh,P) ˆ 141.6 Hz, 2J(P,P) ˆ 23.6 Hz)). It is noteworthy that the
ligand 5 in [Rh(cod)(5)]Cl does not have C2 symmetry. A possible
explanation is that the phosphabicyclo[2.2.1]heptane is too bulkly to
allow the PennPhos to exist in a C2-symmetrical fashion.
aromatic), 3.38 (br d, 2H, 2J(P,H) ˆ 14.2 Hz, PCH), 2.85 (br d, 2H,
2J(P,H) ˆ 13.5 Hz, PCH), 1.85 ± 1.45 (m, 12H), 1.30 ± 1.08 (m, 4H), 1.03
3
3
(d, 6H, J(H,H) ˆ 6.4 Hz, CH3), 0.96 (d, 6H, J(H,H) ˆ 5.6 Hz, CH3), 0.86
(d, 6H, 3J(H,H) ˆ 6.5 Hz, CH3), 0.47 (s, 6H, CH3); 13C NMR (CDCl3): d ˆ
143.97, 143.62, 143.56, 143.50, 143.45, 143.09, 130.96, 130.90, 130.86, 126.11,
54.10, 54.06, 54.03, 48.65, 48.56, 48.46, 42.02, 41.96, 41.24, 41.20, 41.18, 41.14,
37.94, 37.77, 37.60, 37.46, 33.29, 33.27, 33.24, 31.69, 23,45, 23.40, 23.35, 22.22.
20.97, 20.54; 31P NMR (CDCl3): d ˆ 8.7; [a]D ˆ ‡226.7 (c ˆ 1.03, CHCl3);
HR-MS calcd for C30H48P2: 470.3231; found: 470.3229.
General procedure for asymmetric hydrogenation: To
a solution of
[Rh(cod)Cl]2 (2.5 mg, 0.005 mmol) in MeOH (10 mL) was added
5
(3.7 mg, 0.01 mmol). After the reaction mixture was stirred at room
temperature for 10 min, acetophenone (1.0 mmol) was added. The orange-
yellow solution was stirred for 2 min, and the desired amount of the
additive (as a solution in MeOH) was then added. This mixture was stirred
for about 5 min, and hydrogen was introduced. The hydrogenation was
performed in a Parr autoclave at room temperature under 30 atm of
hydrogen for 24 h. The residue was passed through a short silica gel column
to remove the catalyst, and eluted with diethyl ether. The enantiomeric
excesses and reaction conversion were measured by gas chromatography
on a Supelco b-DEX 120 column. The absolute configuration of the
product was determined by comparing the observed rotation with the
reported value.[5c,8d]
Amine Additives Greatly Expand the Scope of
Asymmetric Hydrosilylation of Imines**
Xavier Verdaguer, Udo E. W. Lange, and
Stephen L. Buchwald*
Dedicated to Professor Satoru Masamune
Received: December 19, 1997 [Z11279IE]
German version: Angew. Chem. 1998, 110, 1203 ± 1207
The demand for enantiomerically pure secondary amines
has prompted considerable effort[1] in the development of
catalytic processes for asymmetric hydrogenation[2] and
hydrosilylation[3] of imines. We recently reported a highly
enantioselective titanium-catalyzed hydrosilylation of
imines.[4] This method involves treatment of (S,S)-ethylene-
1,2-bis(h5-4,5,6,7-tetrahydro-1-indenyl)titanium difluoride[5]
(1) with phenylsilane,[4, 6] which yields a very active catalytic
system for the hydrosilylation of N-methyl and cyclic imines
[Eq. (1)]. For example, N-methylimine 2 undergoes complete
hydrosilylation within 12 h at room temperature (Table 1,
entry 1). Although high turnover numbers (up to 5000) and
Keywords: asymmetric catalysis ´ chirality ´ hydrogenations
´ ketones ´ rhodium
[1] a) Catalytic Asymmetric Synthesis (Ed.: I. Ojima), VCH, New York,
1993; b) R. A. Sheldon, Chirotechnology, Marcel Dekker, New York,
1993; c) R. Noyori, Asymmetric Catalysis In Organic Synthesis, Wiley,
New York, 1994.
[2] a) G. Zhu, Z. Chen, Q. Jiang, D. Xiao, P. Cao, X. Zhang, J. Am. Chem.
Soc. 1997, 119, 3836; b) Z. Chen, Q. Jiang, G. Zhu, D. Xiao, P. Cao, C.
Guo, X. Zhang, J. Org. Chem. 1997, 62, 4521.
[3] a) M. J. Burk, J. E. Feaster, R. L. Harlow, Organometallics 1990, 9,
2653; b) M. J. Burk, J. E. Feaster, W. A. Nugent, R. L. Harlow, J. Am.
Chem. Soc. 1993, 115, 10125; c) M. J. Burk, J. R. Lee, J. P. Martinez,
ibid. 1994, 116, 10847.
[4] We abbreviate these chiral ligands as PennPhos to indicate that these
ligands were made at Penn State University.
[5] For aluminum and boron reagents, see a) R. Noyori, I. Tomino, M.
Yamada, M. Nishizawa, J. Am. Chem. Soc. 1984, 106, 6717; b) S.
Masamune, R. M. Kennedy, J. S. Peterson, ibid. 1986, 108, 7404;
c) H. C. Brown, P. V. Ramachadran, Acc. Chem. Res. 1992, 25, 16.
[6] For oxazaborolidine catalysts, see a) S. Itsuno, K. Ito, A. Hirao, S.
Nasahama, J. Chem. Soc. Chem. Commun. 1983, 469; b) E. J. Corey,
R. K. Bakshi, S. Shibata, J. Am. Chem. Soc. 1987, 109, 5551; for
hydrosilylation, see c) H. Brunner, R. Becker, G. Riepl, Organo-
metallics 1984, 3, 1354; d) H. Nishiyama, M. Kondo, T. Nakamura, K.
Itoh, Organometallics 1991, 10, 500; e) M. Sawamura, R. Kuwano, Y.
Ito, Angew. Chem. 1994, 106, 92; Angew. Chem. Int. Ed. Engl. 1994, 33,
111; for tranfer hydrogenation, see f) R. Noyori, S. Hashiguchi, Acc.
[*] Prof. Dr. S. L. Buchwald, Dr. X. Verdaguer, Dr. U. E. W. Lange
Department of Chemistry
Massachusetts Institute of Technology
Cambridge, MA 02139 (USA)
Fax: (‡1)617-253-3297
E-mail: sbuchwal@mit.edu
[**] This work was supported by the National Institutes of Health and
Dow Chemical Company. We thank Boulder Scientific for their
generous gift of chiral metallocene. X.V. thanks the Spanish Ministry
of Education and Science for a postdoctoral fellowship. U.E.W.L.
thanks the Deutsche Forschungsgemeinschaft for a postdoctoral
fellowship. We are grateful to Matthew T. Reding and Malisa V.
Troutman for the preparation of 1, Dr. N. Radu and Professor G. C. Fu
for insightful comments, and Marcus Hansen for experimental help
and discussions.
Â
Chem. Res. 1997, 30, 97; g) D. A. Evans, S. G. Nelson, M. R. Gagne,
A. R. Muci, J. Am. Chem. Soc. 1993, 115, 9800; h) S. Hashiguchi, A.
Fujii, J. Takehara, T. Ikariya, R. Noyori, ibid. 1995, 117, 7562.
[7] a) R. Noyori, Science 1990, 248, 1194; b) R. Noyori, H. Takaya, Acc.
Chem. Res. 1990, 23, 345; c) M. J. Burk, M. F. Gross, G. P. Harper, C. S.
Kalberg, J. R. Lee, J. P. Martinez, Pure Appl. Chem. 1996, 68, 37.
Â
Â
[8] For direct hydrogenation, see a) J. Bakos, I. Toth, B. Heil, L. Marko, J.
Organomet. Chem. 1985, 279, 23; b) A. S. C. Chan, C. R. Landis, J.
Angew. Chem. Int. Ed. 1998, 37, No. 8
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1433-7851/98/3708-1103 $ 17.50+.50/0
1103