H-bonded counterion-directed catalysis (HCDC) is a strategy wherein a chiral anion that is hydrogen-bonded to the achiral ligand of a metal complex is responsible for enantioinduction. In this article we present the application of H-bonded counterion-directed catalysis to the Au(I)-catalyzed enantioselective tandem cycloisomerization-addition reaction of 2-alkynyl enones. Following the addition of C-, N- or O-centered nucleophiles, bicyclic furans were obtained in moderate to excellent yield and enantioselectivity (28 examples, 59–96% yield, 62:38 to 95:5 er). The optimal catalytic system, comprising a phosphinosquaramide Au(I) chloride complex and a BINOL-derived phosphoramidate Ag(I) salt, was selected in a combinatorial fashion from a larger library with the help of high-throughput screening. An enantioselectivity switch of ca 120 Δee% was observed upon addition of the achiral Au(I) component to the Ag(I) salt.
H-Bonded Counterion-Directed Catalysis: Enantioselective Gold(I)-Catalyzed Addition to 2-Alkynyl Enones as a Case Study
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Eur. J. Org. Chem 2022, DOI: 10.1002/ejoc.202200518.