Copper Catalyzed Asymmetric Synthesis of Chiral Allylic Esters

摘要

Enantiomerically pure allylic alcohols and their derivatives are key building blocks in numerous synthetic applications.Besides a number of multistep routes,catalytic methods have been developed involving kinetic resolution or enantioselective addition of alkenyl zinc or boron reagents to carbonyl compounds.Recent breakthroughs for the preparation of optically active allylic alcohol derivatives are based on transition-metal catalyzed allylic substitution using oxygen nucleophiles.Most of these processes give allylic ethers,but the use of carboxylic acids as nucleophiles in the conversion of (Z)-allylic trichloroacetimidates provides allylic esters.Although these methods rely on asymmetric C-O bond formation,we envisioned that the construction of allylic esters through catalytic enantioselective C-C bond formation using simple organometallic reagents might provide a new,general and versatile addition to the current synthetic repertoire.In this context,it should be noted that Trost and Lee reported asymmetric Pd-catalyzed allylic substitutions of geminal dicarboxylates using soft carbon nucleophiles.Herein we report the highly enantioselective synthesis of optically active allylic esters via C-C bond formation in a Cu-catalyzed hetero-allylic asymmetric alkylation (h-AAA) with Grignard nucleophiles (Scheme 1).