Enantioselective Addition of Terminal Alkynes to Aromatic Aldehydes Catalyzed by Copper(I) Complexes with Wide-Bite-Angle Chiral Bisphosphine Ligands: Optimization, Scope, and Mechanistic Studies

The addition of terminal alkynes to aromatic aldehydes was carried out in t-BuOH under mild conditions in the presence of a Cu-phosphine complex, which was prepared in situ from Cu(O-t-Bu) and TRAP chiral bisphosphine, to yield enantiomerically enriched propargyl alcohols with moderate enantioselectivities. Studies on the screening of various ligands showed that wide bite angles of bisphosphine ligands are important for the Cu catalysis. According to the analysis of stoichiometric reactions, the reaction presumably involves the nucleophilic addition of a TRAP-coordinated Cu(I) acetylide to an aldehyde: The alcoholic solvent participates in the addition through coordination to the Cu center and simultaneous protonation of the carbonyl oxygen. The C−C bond-forming addition step is reversible with a strong preference for the backward reaction.