Copper-catalyzed enantioselective allylic alkylation ring-opening reactions of small-ring heterocycles with hard alkyl metals

Abstract

Copper-catalyzed enantioselective allylic substitution reactions with organometallic reagents have aroused a great deal of interest in recent years. Small-ring heterocycles, such as epoxides and aziridines, have proven to be valuable leaving groups in copper-catalyzed asymmetric allylic alkylations with organometallic reagents. Some successful combinations of an organometallic reagent and an external chiral ligand for the enantioselective addition of dialkylzinc reagents to racemic and symmetrical allylic 1,2- and 1,4-epoxides are described. For this purpose, chiral copper complexes of phosphoramidite ligands, having an electron-deficient phosphorus atom, proved to be highly effective catalysts. Our experimental work has shed some light on the mechanism of a copper-catalyzed allylic alkylation and supports the notion that the reductive elimination step is the regio- and stereodetermining step.