Gold(I)-Catalyzed Desymmetrization of Homopropargylic Alcohols via Cycloisomerization: Enantioselective Synthesis of Cyclopentenes Featuring a Quaternary Chiral Center.

Cyclopentene rings possessing a chiral quaternary center are important structural motifs found in various natural products. In this work, we disclose expedient and efficient access to this class of synthetically valuable structures via highly enantioselective desymmetrization of prochiral propargylic alcohols. The efficient chirality induction in this asymmetric gold catalysis is achieved via two-point bindings between a gold catalyst featuring a bifunctional phosphine ligand and the substrate homopropargylic alcohol moiety-an H-bonding interaction between the substrate HO group and a ligand phosphine oxide moiety and the gold-alkyne complexation.

Bifunctional Phosphine-Enabled Regioselective Cycloisomerization of Enynyl Esters En Route to Bicyclo[2.2.1]heptenes.

Expedient access to bridged enol benzoates is realized via a tandem gold-catalyzed cycloisomerization of enynyl esters and the Diels-Alder reaction. The gold catalysis permits the use of enynyl substrates without additional propargylic substitution and achieves the highly regioselective formation of less stable cyclopentadienyl esters. The regioselectivity is enabled by a bifunctional phosphine ligand, the remote aniline group of which facilitates α-deprotonation of a gold carbene intermediate.

Enantioselective Dearomative Cyclization Enabled by Asymmetric Cooperative Gold Catalysis.

A gold(I)-catalyzed enantioselective dearomatization is achieved via metal-chiral ligand cooperation. A new and divergent synthesis of chiral bifunctional binaphthyl-2-ylphosphines is developed to allow rapid access to these ligands, which in turn facilitate the application of this chemistry to a broad substrate scope including 1-naphthols, 2-naphthols, and phenols. Enantiomeric excesses up to 98 % are achieved via selective acceleration of one enantiomer formation enabled by hydrogen bonding between substrate and ligand remote basic group.