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

The highly stereoselective addition of lithiated chloroacetylene, derived in situ from cis-1,2-dichloroethene and methyl lithium, to Ellman chiral N-tert-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 alpha,beta-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.