One-Pot Asymmetric Synthesis of Acyclic Chiral Epoxy Alcohols via Tandem Vinylation−Epoxidation with Dioxygen

[reaction: see text] 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, in most cases, 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.