ORGANIC
LETTERS
2008
Vol. 10, No. 19
4187-4190
Nonracemic Diarylmethanols From
CuH-Catalyzed Hydrosilylation of Diaryl
Ketones
Ching-Tien Lee and Bruce H. Lipshutz*
Department of Chemistry and Biochemistry, UniVersity of California,
Santa Barbara, California 93106
Received July 13, 2008
ABSTRACT
An efficient method for the synthesis of nonracemic diarylmethanols has been developed. The use of (R)-(-)-(DTBM-SEGPHOS)CuH effects
highly enantioselective 1,2-hydrosilylation of prochiral diaryl ketones.
The diarylmethyl moiety, ArAr’CH-, is a common
subunit present in a variety of physiologically active
compounds, such as (R)-neobenodine,1a CDP-840,1b and
tolterodine1c (DetrolLA; Figure 1). It can also be found
in precursors to new ligand scaffolds1d (e.g., tetraaryle-
thanes). Asymmetric inroads to such targets follow several
lines, although most fall within the three broader catego-
ries of (1) biocatalytic reductions,2 (2) diaryl ketone
reductions,3 or (3) 1,2-additions of aryl organometallics
to aryl aldehydes4 (Scheme 1). An extensive review5 by
Bolm and co-workers recently highlighted the role played
by catalysis en route to this functional group array.
Figure 1. Representative bioactive diarylmethanes.
Notably, relatively few reports were quoted involving
transfer hydrogenation beyond the Noyori6 study of 2000
on substituted benzophenones, which occurs under mild
temperatures (23-35 °C) and pressures (8 atm). Even
fewer studies have appeared utilizing an alternative
(1) (a) Rekker, R. F.; Timmerman, H.; Harms, A. F.; Nauta, W. T.
Arzneim.-Forsch. 1971, 21, 688. (b) Alexander, R. P.; Warrellow, G. J.;
Eaton, M. A. W.; Boyd, E. C.; Head, J. C.; Porter, J. R.; Brown, J. A.;
Reuberson, J. T.; Hutchinson, B.; Turner, P.; Boyce, B.; Barnes, D.; Mason,
B.; Cannell, A.; Taylor, R. J.; Zomaya, A.; Millican, A.; Leonard, J.;
Morphy, R.; Wales, M.; Perry, M.; Allen, R. A.; Gozzard, N.; Hughes, B.;
Higgs, G. Bioorg. Med. Chem. Lett. 2002, 12, 1451. (c) Nilvebrant, L.;
Andersson, K.-E.; Gillberg, P.-G.; Stahl, M.; Sparf, B. Eur. J. Pharmacol.
1997, 327, 195. (d) Jen, W. S.; Truppo, M. D.; Amos, D.; Devine, P.;
McNevin, M.; Biba, M.; Campos, K. Org. Lett. 2008, 10, 741.
(2) Truppo, M. D.; Pollard, D.; Devine, P. Org. Lett. 2007, 9, 335.
(3) (a) Corey, E. J.; Helal, C. J. Angew. Chem., Int. Ed. 1998, 37, 1986.
(b) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40. (c) Brown,
E.; Penfornis, A.; Bayma, J.; Touet, J. Tetrahedron: Asymmetry 1991, 2,
339.
(4) (a) Sakai, M.; Ueda, M.; Miyaura, N. Angew. Chem., Int. Ed. 1998,
37, 3279. (b) Huang, W.-S.; Pu, L. J. Org. Chem. 1999, 64, 4222. (c) Bolm,
C.; Muniz, K. Chem. Commun. 1999, 14, 1295. (d) Wu, K.-H.; Gau, H.-M.
J. Am. Chem. Soc. 2006, 128, 14808. (e) Jin, M.-J.; Sarkar, S. M.; Lee,
D.-H.; Qiu, H. Org. Lett. 2008, 10, 1235. (f) Bolm, C.; Rudolph, J. J. Am.
Chem. Soc. 2002, 124, 14850.
(5) Schmidt, F.; Stemmler, R. T.; Rudolph, J.; Bolm, C. Chem. Soc.
ReV. 2006, 35, 454.
(6) Ohkuma, T.; Koizumi, M.; Ikehira, H.; Yokozawa, T.; Noyori, R.
Org. Lett. 2000, 2, 659.
10.1021/ol801590j CCC: $40.75
Published on Web 08/28/2008
2008 American Chemical Society