Direct catalytic asymmetric synthesis of N-heterocycles from commodity acid chlorides by employing α,β-unsaturated acylammonium salts

Abstract

Taming the beast, asymmetrically: Modulation of the reactivity of acid chlorides, using cinchona alkaloid catalysts, results in chiral α,β-unsaturated acylammoniums, which react with nucleophiles enantioselectively to give pyrrolidinones, piperid-2-ones, and dihydropyridinones. This nucleophile-catalyzed Michael/proton transfer/lactamization or lactonization organocascade leads to chiral intermediates previously employed for the synthesis of bioactive pharmaceuticals.

Keywords: enols; heterocycles; natural products; organocatalysis; synthetic methods.