ORGANIC
LETTERS
2004
Vol. 6, No. 17
2937-2940
4,4′-Disubstituted BINAPs for Highly
Enantioselective Ru-Catalyzed
Asymmetric Hydrogenation of Ketones
Aiguo Hu, Helen L. Ngo, and Wenbin Lin*
Department of Chemistry, CB#3290, UniVersity of North Carolina,
Chapel Hill, North Carolina 27599
Received June 1, 2004
ABSTRACT
A family of tunable precatalysts Ru(4,4′-BINAP)(chiral diamine)Cl2 was synthesized and used for highly enantioselective hydrogenation of
aromatic ketones. This result differs from previous chiral diphosphines that rely on the bis(xylyl)phosphino groups to control enantioselectivity.
An X-ray structural study reveals that the bulky substituents on the 4,4′-positions of BINAP can effectively create a suitable chiral pocket in
the transition state and thus provide a new mechanism for the enantiocontrol in such a remarkable asymmetric catalytic process.
Asymmetric hydrogenation of prochiral olefins, ketones, and
imines is one of the most powerful methods for the industrial
production of optically active compounds.1 Among these
methodologies, hydrogenation of simple ketones catalyzed
by the chiral Ru(diphosphine)(diamine)Cl2 system discovered
by Noyori et al. shows the most remarkable enantioselectivity
and activity characteristics.2 Subsequent mechanistic studies
by Noyori et al. and Morris et al. also established a very
unusual catalytic pathway for this remarkable system in
which the key step involves simultaneous transfer of a
hydride on the Ru center and a proton of the RNH2 ligand
to the carbonyl group via a six-membered pericyclic transi-
tion state to afford chiral secondary alcohols.3 Since the
original disclosure in 1995, many chiral diphosphines have
been used to give highly enantioselective Ru(diphosphine)-
(diamine)H2 catalysts for the hydrogenation of simple
ketones.4 Although the enantio-differentiation event has not
been explicitly established, empirical evidence points to the
need of 3,5-dimethylphenyl (xylyl) moieties in all the chiral
(3) (a) Sandoval, C. A.; Ohkuma, T.; Muniz, K.; Noyori, R. J. Am. Chem.
Soc. 2003, 125, 13490-13503. (b) Abdur-Rashid, K.; Clapham, S. E.;
Hadzovic, A.; Harvey, J. N.; Lough, A. J.; Morris, R. H. J. Am. Chem.
Soc. 2002, 124, 15104-15118. (c) Abdur-Rashid, K.; Faatz, M.; Lough,
A. J.; Morris, R. H. J. Am. Chem. Soc. 2001, 123, 7473-7474.
(4) (a) Yu, H.-B.; Hu, Q.-S.; Pu, L. J. Am. Chem. Soc. 2000, 122, 6500-
6501. (b) Henschke, J. P.; Burk, M. J.; Malan, C. G.; Herzberg, D.; Peterson,
J. A.; Wildsmith, A. J.; Cobley, C. J.; Casy, G. AdV. Synth. Catal. 2003,
345, 300-307. (c) Burk, M. J.; Hems, W.; Herzberg, D.; Malan, C.; Zanotti-
Gersosa, A. Org. Lett. 2000, 2, 4173-4176. (d) Wu, J.; Chen., H.; Kwok,
W.-H.; Guo, R.-W.; Zhou, Z.-Y.; Yeung, C. H.; Chan, A. S. C. J. Org.
Chem. 2002, 67, 7908-7910. (e) Wu, J.; Ji, J.-X.; Guo, R.; Yeung, C.-H.;
Chan, A. S. C. Chem. Eur. J. 2003, 9, 2963-2968. (f) Xie, J.-H.; Wang,
L.-X.; Fu, Y.; Zhu, S.-F.; Fan, B.-M.; Duan, H.-F.; Zhou, Q.-L. J. Am.
Chem. Soc. 2003, 125, 4404-4405.
(1) (a) Knowles, W. S. AdV. Synth. Catal. 2003, 345, 3-13. (b) Noyori,
R. Angew. Chem., Int. Ed. 2002, 41, 2008-2022. (c) Ireland, T.; Tappe, K.;
Grossheimann, G.; Knochel, P. Chem. Eur. J. 2002, 8, 843-852.
(2) (a) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J.
Am. Chem. Soc. 1995, 117, 2675-2676. (b) Ohkuma, T.; Ooka, H.; Ikariya,
T.; Noyori, R. J. Am. Chem. Soc. 1995, 117, 10417-10418. (c) Ohkuma,
T.; Koizumi, M.; Doucet, H.; Pham, T.; Kozawa, M.; Murata, K.; Katayama,
E.; Yokozawa, T.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1998, 120,
13529-13530. (d) Ohkuma, T.; Ishii, D.; Takeno, H.; Noyori, R. J. Am.
Chem. Soc. 2000, 122, 6510-6511. (e) Ohkuma, T.; Koizumi, M.; Muniz,
K.; Hilt, G.; Kabuto, C.; Noyori, R. J. Am. Chem. Soc. 2002, 124, 6508-
6509. (f) Doucet, H.; Okhuma, T.; Murata, K.; Yokozawa, T.; Kozawa,
M.; Katayama, E.; England, A. F.; Ikariya, T.; Noyori, R. Angew. Chem.,
Int. Ed. 1998, 37, 1703-1707.
10.1021/ol048993j CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/20/2004