The Enantioselective TCDC approach in Au(I)-Catalysis: Insights into the Reactions between 2-Alkynyl Ketones and Naphthols

The enantioselective tandem cycloisomerization / addition reactions of 2-alkynyl enones with 1- and 2-naphthols have been investigated using gold(I) catalysts featuring hybrid phosphine-phosphoric acid ligands, according to the Tethered Counteri-on-Directed Catalysis strategy. The reactions occur at low catalytic loading (0.2-1 mol%), without silver additives, and the naphthols act as both O- and C-nucleophiles, leading to the corresponding addition products in high yields and enantioselec-tivities. Monitoring of the reaction course highlights both conversion of O-addition into C-addition products and racemiza-tion processes that can affect the enantiomeric excess of the final products. Examples of solvent-dependent enantiodiver-gence, as well as further conversion of the C-addition products into highly enantioenriched heteropolycycles are shown.