Highly diastereoselective synthesis of α-trifluoromethylated α-propargylamines by acetylide addition to chiral CF3-substituted N-tert-butanesulfinyl ketimines

A convenient and practical method for the preparation of enantiomerically pure alpha-trifluoromethylated alpha-propargylamines is described. A range of enantiopure alpha-trifluoromethylated alpha-propargyl sulfinamides were obtained by the addition of lithium acetylides generated in situ with n-BuLi and terminal alkynes to diverse chiral CF3-substituted (S)-N-tert-butanesulfinyl ketimines in moderate to excellent yields (56-97%) and with uniformly excellent diastereoselectivities (>99:1) by using Ti((OPr)-Pr-i)(4) as the catalyst and THF as the polar solvent. Enantiomerically pure alpha-trifluoromethylated alpha,alpha-dibranched propargyl amines were then readily obtained in excellent yields (87-97%) by acidic cleavage of the tert-butanesulfinyl group. (C) 2010 Elsevier Ltd. All rights reserved.