Enantioselective one-pot three-component synthesis of propargylamines catalyzed by copper(I)-pyridine bis-(oxazoline) complexes

A one-pot three-component coupling of aldehydes and amines in presence of terminal alkynes has been efficiently catalyzed by copper (I) complex of i-Pr-pybox-diPh 2b or s-Bu-pybox-diPh 2c. The process is simple and allows the synthesis of various propargylamines in good to excellent enantioselectivities (up to 99% ee) and in higher yields. The nature of the substituents attached to imines plays a vital role on the enantioselectivities obtained. The presence of gem-diphenyl group at C-5 position and secondary alkyl substituents at the C-4 chiral center of the oxazoline rings of the chiral ligands was found to be crucial for higher enantioselectivities. A transition state model involving pi-pi stacking is also proposed for the stereochemical outcome. (C) 2011 Elsevier Ltd. All rights reserved.