ORGANIC
LETTERS
2000
Vol. 2, No. 15
2377-2379
Dynamic Kinetic Resolution of Allylic
Alcohols Mediated by Ruthenium- and
Lipase-Based Catalysts
Donghyun Lee, Eun A. Huh, Mahn-Joo Kim,* Hyun Min Jung,
Jeong Hwan Koh, and Jaiwook Park*
Department of Chemistry, DiVision of Molecular and Life Science, Pohang UniVersity
of Science and Technology, San 31 Hyojadong, Pohang, Kyungbuk 790-784, Korea
Received June 5, 2000
ABSTRACT
An enzyme−metal combo reaction has been developed for the dynamic kinetic resolution of allylic alcohols in which racemic substrates are
transformed by a lipase and a ruthenium complex in the presence of an acyl donor to allylic acetates of high optical purity in over 80% yield.
We and others are developing enzyme/metal combo reactions
(EMCRs) as a new methodology for the synthesis of
homochiral compounds.1,2 In this Letter, we describe an
EMCR for the dynamic kinetic resolution (DKR) of allylic
alcohols in which racemic substrates are enantioselectively
acetylated by a lipase with the in situ racemization of
unreacted substrates by a ruthenium complex to give allylic
acetates of high optical purity in over 80% yields.
acylation.4 However, these procedures suffer from a disad-
vantage that the theoretical maximum yield is limited to 50%.
This problem can be overcome if an efficient DKR procedure
is developed.5 We recently reported an EMCR for the DKR
of racemic allylic acetates in which racemic substrates were
converted by a lipase in the presence of a palladium complex
to single enantiomers of allylic alcohols1a,2c (Scheme 1).
Chiral allylic alcohols and acetates in optically pure forms
are useful synthons which can be transformed to a wide range
of more complex molecules.3 Among the methods currently
available for the synthesis of the allylic compounds, two of
the most practical are the kinetic resolutions of racemic allylic
alcohols by asymmetric epoxidation3a and by enzymatic
Scheme 1. EMCR for the DKR of Allylic Acetates
(1) (a) Choi, Y.-K.; Suh, J. H.; Lee, D.; Lim, I.; Jung, J. Y.; Kim, M.-J.
J. Org. Chem. 1999, 64, 8423. (b) Koh, J. H.; Jung, H. M.; Kim, M.-J.;
Park, J. Tetrahedron Lett. 1999, 40, 6281. (c) Jung, H. M.; Koh, J. H.;
Kim, M.-J.; Park, J. Org. Lett. 2000, 2, 409. (d) Jung, H. M.; Koh, J. H.;
Kim, M.-J.; Park, J. Submitted.
(2) (a) Dinh, P. M.; Howarth, J. A.; Hudnott, A. R.; Williams, J. M. J.;
Harris, W. Tetrahedron Lett. 1996, 37, 7623. (b) Reetz, M. T.; Schimossek,
K. Chimia 1996, 50, 668. (c) Allen, J. V.; Williams, J. M. J. Tetrahedron
Lett. 1996, 37, 1859. (d) Persson, B. A.; Larsson, A. L. E.; Ray, M. L.;
Ba¨ckvall, J.-E. J. Am. Chem. Soc. 1999, 121, 1645. (e) Huerta, F. F.; Laxmi,
Y. R. S.; Ba¨ckvall, J.-E. Org. Lett. 2000, 2, 1037.
(3) (a) Johnson, R. A.; Sharpless, K. B. In ComprehensiVe Organic
Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, 1991; Vol. 7, p 389. (b)
Jonson, R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis; Ojima,
I., Ed.; VCH: New York, 1993; Chapter 4. (c) Heck, R. F. Palladium
Reagents in Organic Synthesis; Academic: London, 1985; Chapter 5. (d)
Tsuji, J. Palladium Reagents and Catalysts; John Wiley & Sons: Chichester,
1997; Chapter 4.
Subsequently, we became interested in an EMCR for the
reverse reaction as a useful alternative for the synthesis of
homochiral allylic acetates.
Previously, ruthenium complexes 1 and 2 were proved to
be efficient racemization catalysts for the DKRs of simple
secondary alcohols.1b,2d-e These ruthenium catalysts, how-
ever, were not appropriate as racemization catalysts for the
10.1021/ol006159y CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/06/2000