Tandem Desymmetric Condensation and Oxidative Cyclization to Construct Chiral 4-Carbonyl-quinoline Fused Cyclobutanones Bearing a Quaternary Carbon Center

A catalytic desymmetric tandem carbonyl-amine condensation and oxidative cyclization reaction between 2-alkylaniline and prochiral 1,3-cyclobutadiones is developed to synthesize chiral 4-carbonyl-quinoline fused cyclobutanones bearing a quaternary carbon center in good to high yields with up to 94% ee values. This one-pot annulation sequence represents the first application of Cu-catalyzed oxidative cyclization of the N-(2-alkynylaryl)enamine intermediate to construct chiral polycyclic quinoline derivatives. Preliminary mechanistic studies supported the radical process nature of the oxidative cyclization step.