Asymmetric synthesis of propargylic alcohols via aldol reaction of aldehydes with ynals promoted by prolinol ether–transition metal–Brønsted acid cooperative catalysis

A catalytic and highly stereoselective entry to propargylic alcohols and products derived thereof is reported based on an unprecedented cross-aldol coupling between unmodified aldehydes and ynals. The method requires an amine-metal salt-Bronsted acid ternary catalyst system and implies synergistic activation of the donor aldehyde via enamine and of the acceptor carbonyl via unique and reversible metal-alkyne complexation. Specifically, by using a combined alpha,alpha-dialkylprolinol silyl ether-CuI-PhCO2H catalyst system, remarkably high levels of diastereo- and enantioselectivity (anti/syn up to >20 : 1, ee up to >99%) are achieved.