Catalytic asymmetric Nakamura reaction by gold(I)/chiral N,Nʹ-dioxide-indium(III) synergistic catalysis

Intermolecular addition of enols and enolates to unactivated alkynes was proved to be a simple and powerful method for carbon-carbon bond formation. Up to date, a catalytic asymmetric version of alkyne with 1,3-dicarbonyl compound has not been realized. Herein, we achieve the first catalytic asymmetric intermolecular addition of 1,3-dicarbonyl compounds to unactivated 1-alkynes. A range of β-ketoamides with a cyclic all-carbon quaternary center and acyclic quaternary center with a fluorine substituent were synthesized in excellent yields with good enantioselectivities attributing to the synergistic activation of chiral N,N′-dioxide-indium(III) Lewis acid and achiral gold(I) π-acid. Besides, a possible catalytic cycle and transition state models were proposed to illustrate the origin of process based on the experimental investigations.