One-pot asymmetric synthesis of acyclic epoxy alcohols via tandem vinylation-epoxidation with dioxygen

ORGN 114

Alice E. Lurain, Patrick J. Carroll, and Patrick J. Walsh. Department of Chemistry, University of Pennsylvania, 231 S. 34th Street, Philadelphia, PA 19104
We have developed a one-pot procedure for the asymmetric synthesis of a synthetically challenging class of acylic secondary epoxy alcohols with three contiguous stereocenters from simple achiral starting materials. The epoxy alcohols are synthesized via a tandem catalytic asymmetric vinylation of an aldehyde coupled with a diastereoselective epoxidation reaction. A vinylzinc reagent generated in situ undergoes enantioselective addition to an aldehyde in the presence of a zinc catalyst to provide an allylic zinc alkoxide. This species is then epoxidized by addition of dioxygen and a titanium-tartrate catalyst to give epoxy alcohols with excellent enantioselectivities and with diastereoselectivities up to 4.5:1 in favor of the threo diastereomer. The system described herein represents a significant advance in terms of synthetic efficiency and selectivity.