Enantioselective Synthesis of 2-Substitued-Tetrahydroisoquinolin-1-yl Glycine Derivatives via Oxidative Cross-Dehydrogenative Coupling of Tertiary Amines and Chiral Nickel(II) Glycinate

Abstract

The asymmetric synthesis of 2-substituted-tetrahydroisoquinolin-1-yl glycines was achieved by an oxidative cross-dehydrogenative coupling (CDC) reaction. This method for activation of the α-C-H bonds of amines with chiral nickel(II) glycinate using o-chloranil as the sole oxidant afforded highly diastereoselective coupling adducts. The decomposition of coupling adducts readily afforded 2-substituted-tetrahydroisoquinolin-1-yl glycine derivatives.