Highly Stereoselective Synthesis of Terminal Chloro-Substituted Propargylamines and Further Functionalization

Abstract

The highly stereoselective addition of lithiated chloroacetylene, derived <i>in situ</i> from <i>cis</i>-1,2-dichloroethene and methyl lithium, to Ellman chiral <i>N</i>-<i>tert</i>-butanesulfinyl imines is reported. The reaction proceeds in high yield (up to 98%) and with excellent diastereoselectivity (up to >20:1) for a variety of aryl, heteroaromatic, alkyl, and α,β-unsaturated imine substrates. Transformations of the terminal chloro-substituted propargylamine products are described in which lithium–halogen exchange yields nucleophilic acetylides that can be quenched to yield terminal alkynes or intercepted by carbon electrophiles