J . Org. Chem. 1999, 64, 2127-2129
2127
Ru -BICP -Ca ta lyzed Asym m etr ic
Hyd r ogen a tion of Ar om a tic Keton es
Ping Cao and Xumu Zhang*
Department of Chemistry, 152 Davey Laboratory,
The Pennsylvania State University,
F igu r e 1.
University Park, Pennsylvania 16802
Sch em e 1
Received September 14, 1998
In tr od u ction
The design and synthesis of effective enantioselective
catalysts for hydrogenation of simple ketones remains a
challenging problem.1 Recently, Noyori2 disclosed a ter-
nary catalyst system consisting of Ru-BINAP-chiral
diamine-KOH, which is highly efficient in the asym-
metric hydrogenation of a variety of simple ketones
lacking a secondary coordinating functional group. We
have developed rhodium complexes with a conformation-
ally rigid, electron-rich bidentate phosphine ligand (Penn-
Phos)3 as highly enantioselective catalysts for hydrogena-
tion of both aryl alkyl and dialkyl ketones. In a related
study, we have designed and synthesized a new confor-
mationally rigid 1,4-bisphosphine, (2R,2′R)-bis(diphe-
nylphosphino)-(1R,1′R)-dicyclopentane (BICP). Rh-BICP
gives excellent enantioselectivity upon asymmetric hy-
drogenation of 2-(acylamino)acrylic acids.4 Prompted by
these encouraging results, we were interested in explor-
ing the Ru-BICP-catalyzed hydrogenation of simple
ketones using Noyori’s protocol (Scheme 1). Our experi-
mental results on a Ru-BICP catalytic system indicate
an important finding of possible multipoint interactions
between a chiral chelating diamine and acetylthiophene
derivatives.
be synthesized by reacting [Ru(η3-methyl-allyl)2(COD)]
with BICP in acetone, followed by addition of 2 equiv of
methanolic HCl. The catalyst precursor made from this
RuCl2[(R,R)-BICP] recipe in combination with 1 equiv of
(R,R)-1,2-diphenylethylenediamine is also suitable for
asymmetric hydrogenation of aromatic ketones. In this
work, we typically used RuCl2[(R,R)-BICP](TMEDA)
made from the [Ru(η6-cymene)Cl]2 precursor for catalytic
reactions because it has higher activity toward hydroge-
nation of ketones.
We chose acetophenone as a typical substrate and the
hydrogenation reaction was performed in 2-propanol
under 60 psi of H2 at room temperature with 0.2 mol %
of catalyst. The Ru-BICP catalyst was generated in situ
from three components: RuCl2[(R,R)-BICP](TMEDA),
(R,R)-1,2-diphenylethylenediamine and KOH (molar
ratio 1:1:2). Under these conditions, hydrogenation of
acetophenone gave 1-phenylethanol in 72% ee. Varying
the solvent or H2 pressure had only a small effect on the
enantioselectivity. At -20 °C, a slightly higher ee (78%)
was obtained. The match of the steric environment of the
chiral diamine with that of the chiral bisphosphine BICP
is important for achieving high enantioselectivity, which
is consistent with Noyori’s observation.2 For example,
combination of (S,S)-1,2-diphenylethylenediamine and
RuCl2[(R,R)-BICP](TMEDA) resulted in only 36% ee
upon hydrogenation of acetophenone. Switching from
(R,R)-1,2-diphenylethylenediamine to (R,R)-1,2-cyclohex-
anediamine gave lower enantioselectivity (57% ee).
Table 1 summarizes the hydrogenation results with
aryl alkyl ketones under the optimized conditions. Sub-
stitution on the 4′-position of the benzene ring with
electron-withdrawing groups has only a small effect on
the enantioselectivity (73-76% ee, entries 1-3). Varia-
tion of the structure of the alkyl groups on the ketones
causes major changes in the observed enantioselectivity
(76% ee, entry 1, 79% ee, entry 5, 26% ee, entry 6). A
change in the steric environment on the aromatic ring
also results in a big difference in the activity and
enantioselectivity of this catalytic system. For example,
Resu lts a n d Discu ssion
We have prepared several Ru-BICP complexes and
probed their catalytic activity and enantioselectivity for
hydrogenation of simple ketones. The Ru-BICP precata-
lyst (I, Figure 1) was prepared by combining RuCl2[(R,R)-
BICP](TMEDA) with 1 equiv of (R,R)-1,2-diphenylethyl-
enediamine in 2-propanol. [Ru(η6-cymene)Cl2]2, [Ru(η6-
benzene)Cl2]2, and [(COD)RuCl2]n all can be used to
prepare RuCl2[(R,R)-BICP](TMEDA) according to a lit-
erature procedure.5 Alternatively, RuCl2(R,R)-BICP6 can
(1) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis; J ohn
Wiley & Sons: New York, 1994. (b) Catalytic Asymmetric Synthesis;
Ojima, I., Ed.; VCH: New York, 1993. (c) Noyori, R.; Hashiguchi, S.
Acc. Chem. Res. 1997, 30, 97. (d) Fehring, V.; Selke, R. Angew. Chem.,
Int. Engl. Ed. 1998, 37, 1827. For early examples of direct asymmetric
hydrogenation, see: (e) Bakos, J .; To´th, I.; Heil, B.; Marko´, L. J .
Organomet. Chem. 1985, 279, 23. (f) Chan, A. S. C.; Landis, C. R. J .
Mol. Catal. 1989, 29, 165. (g) Zhang, X.; Taketomi, T.; Yoshizumi, T.;
Kumobayashi, H.; Akutagawa, S.; Mashima, K.; Takaya, H. J . Am.
Chem. Soc. 1993, 115, 3318.
(2) (a) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori,
R. J . Am. Chem. Soc. 1995, 117, 2675. (b) Doucet, H.; Ohkuma, T.;
Murata, K.; Yokozawa, T.; Kozawa, M.; Katayama, E.; England, A. F.;
Ikariya, T.; Noyori, R. Angew. Chem., Int. Engl. Ed. 1998, 37, 1703
and references therein.
(3) J iang, Q.; J iang, Y.; Xiao, D.; Cao, P.; Zhang X. Angew. Chem.,
Int. Engl. Ed. 1998, 37, 1100.
(4) Zhu, G.; Cao, P.; J iang, Q.; Zhang, X. J . Am. Chem. Soc. 1997,
119, 1799.
(5) Kitamura, M.; Tokunaga, M.; Ohkuma, T.; Noyori, R. Org. Synth.
1993, 71, 1.
(6) Geneˆt, J . P.; Pinel, C.; Ratovelomanana-Vidal, V.; Mallart, S.;
Pfister, X.; Bischoff, L.; Can˜o De Andrade, M. C.; Darses, S.; Galopin,
C.; Laffitte, J . A. Tetrahedron: Asymmetry 1994, 5, 675.
10.1021/jo981859q CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/19/1999