Novel developments in the asymmetric reduction of enones to allylic alcohols: Preparation of allylic alcohol intermediates in the syntheses of a_vb₃–inhibitors

ORGN 7

J. Christopher McWilliams1, Elizabeth Buck1, Kan K. Eng1, Roger N. Farr1, Edward J. J. Grabowski1, Guy R. Humphrey1, Joseph Lynch1, David J. Pollard2, Jess W. Sager1, Kathleen Telari2, and Marjorie M. Waters1. (1) Department of Process Research and the Catalytic Reactions Discovery and Development Laboratory, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, (2) Department of Bioprocess Research and Development, Merck Research Laboratories, 126 Lincoln Ave, Rahway, NJ 07065

The syntheses of key allylic alcohol intermediates in the preparation of avb3–inhibitors were achieved by asymmetric reduction of the corresponding enones via three distinct chemical/biochemical methods. This presentation will describe novel developments in each of these procedures that resulted in increases to the overall yields and enantioselectivities. Highlighted will be the use of additives to modify a BINAL–H reagent, the use of selective inhibitors in a whole cell bioreduction, and the development of a ²buffered² solvent system amenable to the asymmetric hydrogenation of this sensitive functionality.

Asymmetric Reactions and Syntheses 8:00 AM-12:00 PM, Sunday, September 7, 2003 Sheraton New York -- Imperial Ballroom A, Oral Division of Organic Chemistry The 226th ACS National Meeting, New York, NY, September 7-11, 2003