Zinc salt promoted diastereoselective synthesis of chiral propargylamines using chiral piperazines and their enantioselective conversion into chiral allenes

Abstract

Zinc chloride catalyzed reactions of chiral piperazine derivatives 4a-d with 1-alkynes and aldehydes give chiral propargylamines in 67-95 % yields with up to 99:1 dr. The chiral propargylamines are converted into chiral allenes by using zinc bromide in short reaction times (1-2 h) in high enantioselectivities (up to 99 % ee) in good yields (up to 89 %). The chiral piperazines are recovered in good yields (79-86 %) by reduction of the imine byproducts in situ by using NaBH4. Unexpectedly, the chiral aryl-substituted allenes undergo facile cyclodimerization under neat conditions at 25 C, in contrast to an earlier report that cyclodimerization takes place at 80 C in benzene, which further illustrates the importance of the two-step procedure reported herein because the chiral propargylamine may be converted into chiral allene when required.