J. Am. Chem. Soc. 1998, 120, 13529-13530
Asymmetric Hydrogenation of Alkenyl, Cyclopropyl,
13529
and Aryl Ketones. RuCl2(xylbinap)(1,2-diamine) as a
Precatalyst Exhibiting a Wide Scope
†
,‡
†
†
Takeshi Ohkuma, Masatoshi Koizumi, Henri Doucet,
†
‡
‡
Trang Pham, Masami Kozawa, Kunihiko Murata,
Eiji Katayama, Tohru Yokozawa, Takao Ikariya, and
‡
‡
‡
Ryoji Noyori*,
†,‡
Department of Chemistry and Research Center for
Materials Science, Nagoya UniVersity
Chikusa, Nagoya 464-8602, Japan
ERATO Molecular Catalysis Project
Japan Science and Technology Corporation
247 Yachigusa, Yakusa-cho, Toyota 470-0392, Japan
1
sensitivity to basic conditions. Now the combined use of trans-
ReceiVed September 14, 1998
3
RuCl (xylbinap)(1,2-diamine) (1) (1,2-diamine ) DAIPEN,
2
3
trans-RuCl
2
(phosphine)
2
(1,2-diamine), when coupled with a
2 3
trans-cyclohexane-1,2-diamine, DPEN ) and K CO , a weak base
cocatalyst in place of conventional KOH or KOC(CH ) ,
1
,2,4
strong base in 2-propanol, acts as the most reactive catalyst for
has
3
3
1
homogeneous hydrogenation of ketones. Use of a chiral diphos-
solved this long-standing problem. The hydrogenation of benzal-
phine and diamine ligand allows a rapid, productive, and
enantioselective hydrogenation of simple ketones having no
second heteroatom functionality. The asymmetric hydrogenation
of certain aromatic ketones has achieved a TON (mols of product
acetone (2a) (100 g) in 2-propanol (150 mL) containing (S,S)-1a
-1
per mol of catalyst) as high as 2 400 000 and a TOF (TON sec
)
1
of 72. Furthermore, this reaction, unlike conventional hydrogena-
tions, proceeds selectively at a CdO bond leaving coexisting
2
CdC linkages intact. However, no single asymmetric catalyst
can be universal, since there exist a structurally diverse array of
ketones. To secure high enantioselection, a proper catalyst as well
as appropriate reaction conditions must be selected, depending
on the properties of substrates. This hydrogenation system can
flexibly cope with diverse situations by modifying catalyst
structures and reaction parameters. Although the original BINAP/
(
2
°
(
8.3 mg) and K
.7 M solution) at 80 atm (or 10 atm with S/C ) 10000) and 30
C for 43 h afforded quantitatively (R)-3a in 97% ee (cf. 65% ee
2 3
CO (9.4 g) (substrate/catalyst (S/C) ) 100000,
3
DPEN-based catalysts had a limited scope for substrates display-
1
,2,4
ing sufficiently high enantioselectivity,
we have now found
7
2
Ir) and 70% ee (Ru) in earlier works). No trace of CdC
5
that the use of XylBINAP as a chiral diphosphine increases the
enantioselectivity for many substrates and that the structures of
chiral 1,2-diamines fine-tune the extent of the selectivity. This
new system not only enhances the enantioselectivity of the known
asymmetric hydrogenation but also expands the synthetic scope
to a great extent.
reduction products were detected, despite the eminent catalytic
activity of diamine-free BINAP-Ru complexes for hydrogenation
of the CdC unit of allylic alcohols. Highly base-sensitive
10
3
-nonen-2-one (2c) (0.1 M solution) was equally converted to 3c
with 97% ee. Hydrogenation of the enone 2d catalyzed with (R,R)-
a gave (S)-3d with 90% ee, a key building block for preparation
1
Chiral allylic alcohols are important not only for their own
11
of a vitamin E side chain. As listed in Table 1, flexible enones
with various substitution patterns were hydrogenated to allylic
alcohols in high enantiomeric purity.
sake but also in connection with the Claisen technology.6
However, the enantioselective hydrogenation of simple R,â-
unsaturated ketones (eq 1) has remained difficult2
,7-9
because of
Hydrogenation of cyclopropyl methyl ketone (4a) in the
the conformational flexibility of the substrates as well as the high
3 3
presence of (S,S)-1a and KOC(CH ) gave (R)-5a in 95% ee
†
‡
without cleavage of the three-membered ring (eq 2) (Table 1). In
Nagoya University.
ERATO Molecular Catalysis Project.
(
1) Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa, T.; Kozawa, M.;
Katayama, E.; England, A. F.; Ikariya, T.; Noyori, R. Angew. Chem., Int. Ed.
1
1
2
998, 37, 1703-1707.
2) Ohkuma, T.; Ooka, H.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1995,
17, 10417-10418.
3) BINAP ) 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl. TolBINAP )
,2′-bis(di-4-tolylphosphino)-1,1′-binaphthyl. DPEN ) 1,2-diphenylethylene-
(
(
diamine. DAIPEN ) 1,1-dianisyl-2-isopropyl-1,2-ethylenediamine.
(4) (a) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J.
Am. Chem. Soc. 1995, 117, 2675-2676. (b) Ohkuma, T.; Ooka, H.;
Yamakawa, M.; Ikariya, T.; Noyori, R. J. Org. Chem. 1996, 61, 4872-4873.
comparison, cyclohexyl methyl ketone formed an R alcohol in
(5) Xyl refers to 3,5-xylyl (3,5-dimethylphenyl). XylBINAP ) 2,2′-bis-
(8) (a) Terashima, S.; Tanno, N.; Koga, K. J. Chem. Soc., Chem. Commun.
1980, 1026-1027. (b) Brown H. C.; Pai, G. G. J. Org. Chem. 1982, 47, 1608-
1610. (c) Noyori, R.; Tomino, I.; Yamada, M.; Nishizawa, M. J. Am. Chem.
Soc. 1984, 106, 6717-6725.
(
di-3,5-xylylphosphino)-1,1′-binaphthyl. See: Mashima, K.; Kusano, K.; Sato,
N.; Matsumura, Y.; Nozaki, K.; Kumobayashi, H.; Sayo, N.; Hori, Y.; Ishizaki,
T.; Akutagawa, S.; Takaya, H. J. Org. Chem. 1994, 59, 3064-3076.
(6) Pertinent reviews: (a) Wipf, P. In ComprehensiVe Organic Synthesis;
(9) Corey, E. J.; Helal, C. J. Angew. Chem., Int. Ed. 1998, 37, 1986-
2012, and references therein.
(10) Takaya, H.; Ohta, T.; Sayo, N.; Kumobayashi, H.; Akutagawa, S.;
Inoue, S.; Kasahara, I.; Noyori, R. J. Am. Chem. Soc. 1987, 109, 1596-1597,
4129.
(11) Chan, K.-K.; Cohen, N.; De Noble, J. P.; Specian, A. C., Jr.; Saucy,
G. J. Org. Chem. 1976, 41, 3497-3505.
Trost, B. M., Fleming, I., Paquette, L. A., Eds.; Pergamon Press: Oxford,
991; Vol. 5, Chapter 7.2. (b) Frauenrath, H. In Methods of Organic Chemistry
Houben-Weyl), 4th ed.; Helmchen, G.; Hoffmann, R. W.; Mulzer, J.;
Schaumann, E., Eds.; Thieme: Stuttgart, 1995; Vol. E21d, Chapter 1.6.3.1.1.
7) Mashima, K.; Akutagawa, T.; Zhang, X.; Takaya, H.; Taketomi, T.;
Kumobayashi, H.; Akutagawa, S. J. Organomet. Chem. 1992, 428, 213-222.
1
(
(
1
0.1021/ja983257u CCC: $15.00 © 1998 American Chemical Society
Published on Web 12/10/1998