Propargylic Alcohol as a Key Substrate Motif for Achieving Enantioselective Gold-Catalyzed Enyne Cycloisomerization

Abstract

Despite successes in achieving asymmetric induction in enyne cycloisomerization, few systems are applicable to each of the typical 6-endo, 5-exo, and 5-endo cyclization/cycloisomerization modes. By appending a synthetically valuable hydroxymethyl group at the alkyne end, a hydrogen bond between the HO group of the propargyl alcohol moiety and a chiral ligand basic group offers a novel asymmetric induction strategy in gold-catalyzed enyne cycloisomerization reactions. Both 1,5-enynes and 1,6-enynes are suitable substrates, and 5-exo, 5-endo, and 6-exo cyclizations lead to outstanding enantioselectivities. As a valuable reactive moiety, the hydroxymethyl group is converted into a versatile aldehyde moiety in the exo cyclization modes or engages in enantioselective cyclizations in a ligand-dictated chemodivergent process. This strategy may further advance asymmetric gold catalysis.