Catalytic asymmetric Nakamura reaction by gold(I)/chiral N,N'-dioxide-indium(III) or nickel(II) 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 catalytic asymmetric intermolecular addition of 1,3-dicarbonyl compounds to unactivated 1-alkynes attributing to the synergistic activation of chiral N,N-dioxide-indium(III) or nickel(II) Lewis acid and achiral gold(I) pi -acid. A range of beta -ketoamides, beta -ketoesters and 1,3-diketones transform to the corresponding products with a tetra-substituted chiral center in good yields with good e.r. values. Besides, a possible catalytic cycle and a transition state model are proposed to illustrate the reaction process and the origin of chiral induction based on the experimental investigations.Although enols and enolates addition to unactivated alkynes is used for carbon-carbon bond modification a catalytic asymmetric alkyne with 1,3-dicarbonyl compound has been elusive. Here, the authors achieve this using the synergistic activation of chiral N,N ' -dioxide-indium(III) or nickel(II) Lewis acid and achiral gold(I) pi -acid.

Automated summary

This study demonstrates the catalytic asymmetric intermolecular addition of 1,3-dicarbonyl compounds to unactivated 1-alkynes through the synergistic activation of chiral N,N'-dioxide-indium(III) or nickel(II) Lewis acid and achiral gold(I) π-acid. A potential catalytic cycle and transition state model were proposed based on experimental investigations.