Enantioselective Cu-catalyzed decarboxylative propargylic amination of propargyl carbamates

A copper-catalyzed asymmetric propargylic amination with a chiral ketimine P,N,N-ligand that proceeds via decarboxylation of propargyl carbamates has been developed. The reaction can be performed under the mild condition for a broad range of substrates, providing the corresponding propargylic amines in high yields and with up to 97% ee. This reaction represents a new and facile access to optically active propargylic amines. 2014 Elsevier Ltd. All rights reserved. Chiral propargylic amines are widely used as intermediate products in the preparation of biologically active compounds and polyfunctional amino derivatives. Among various methods for the synthesis of these compounds, catalytic asymmetric propargylic amination should be one of the most attractive strategies. Although great progress has been made in the transition-metal catalyzed propargylic substitution in the past decades, the synthesis of chiral propargylic amines via the catalytic asymmetric propargylic amination is still highly limited. In 1994, Murahashi and co-workers found that propargylic amines could be obtained via the copper-catalyzed propargylic amination of propargylic esters with various amines, which sets the stage for the development of an asymmetric version. In 2008, van Maarseveen and co-workers and Nishibayashi and co-workers independently reported the first copper-catalyzed asymmetric propargylic amination of propargylic acetates with primary amines and secondary amines, respectively. Following them, some copper-catalyzed asymmetric propargylic aminations have been reported. Despite these advances, the development of a new strategy for the catalytic asymmetric synthesis of optically active propargylic amines remains a highly desirable and challenging task. Very recently, we have reported the first copper-catalyzed asymmetric decarboxylative propargylic alkylation of propargyl b-ketoesters. In this method, the loss of CO2 replaces the need to selectively prepare preformed enolate equivalents, and both the nucleophile and the electrophile are formed in situ in catalytic concentration. The reaction could be performed under the mild condition, and proceeded in highly enatioselective form. We envisaged that this strategy should also provide an ideal solution for the synthesis of optically active propargylic amines if a propargyl carbamate is employed as the substrate instead of propargyl b-ketoester (Scheme 1). As a result, herein we described the first enantioselective copper-catalyzed decarboxylative propargylic amination of propargyl carbamates with a tridentate ketimine P,N,N-ligand, in which excellent performance could be achieved (Fig. 1). The corresponding propargyl carbamates can be easily prepared by the reaction of carbamic chlorides with various substituted