Enantioselective Synthesis of 2-Substitued-Tetrahydroisoquinolin

Enantioselective Synthesis of 2-Substitued-Tetrahydroisoquinolin-1-yl Glycine Derivatives via Oxidative Cross-Dehydrogenative Coupling of Tertiary Amines and Chiral Nickel(II) Glycinate
Shengbin Zhou , Jiang Wang , Daizong Lin , Fei Zhao , and Hong Liu
J. Org. Chem., Just Accepted Manuscript
DOI: 10.1021/jo401510b
Publication Date (Web): October 11, 2013
Copyright © 2013 American Chemical Society

The asymmetric synthesis of 2-substituted-tetrahydroisoquinolin-1-yl glycine was achieved by an oxidative cross-dehydrogenative coupling (CDC) reaction. This method for activation of the alpha-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.