Highly Site- and Enantioselective Cu-Catalyzed Allylic Alkylation Reactions with Easily Accessible Vinylaluminum Reagents

Abstract

An efficient method for catalytic asymmetric allylic alkylation (AAA) of allylic phosphates with vinylaluminum reagents is reported. The vinylmetal reagents are prepared by reaction of commercially available DIBAL-H and a terminal alkyne. The resulting vinylaluminum reagent can be used directly, without isolation or purification. AAA reactions are promoted in the presence of 0.5−2.5 mol % of a readily available chiral N-heterocyclic carbene (NHC) complex and 1−5 mol % commercially available and air stable Cu salt (CuCl2·2H2O). The desired products are typically obtained within 2−12 h in 74% to 95% isolated yield, 77% to >98% ee, and in >98% E selectivity; >98% SN2‘ selectivity is obtained in all but one instance (90%). The hydroalumination/catalytic AAA sequence can be performed in a single vessel, on gram scale.