Catalytic synthesis of nonracemic azaproline derivatives by cyclization of β-alkynyl hydrazines under kinetic resolution conditions.

Heteroatom addition reactions to unactivated alkynes are thought to be best mediated by transition-metal catalysts such as palladium and gold. Recent studies by Hammond and co-workers and others demonstrate that cyclizations of alkynes with nitrogenand oxygen-containing nucleophiles are possible using stoichiometric amounts of tetra-n-butylammonium fluoride. However, these examples appear to be limited to aryl or a,a-difluoro alkynes. As described herein, we have discovered by serendipity a nonmetal catalyzed addition of amine to unactivated alkynes to yield azaproline derivatives (Scheme 1). Although the nature of this catalysis reaction is not clear, these reactions proceed in excellent yields and lead to enantioenriched azaprolines under kinetic resolution conditions using ammonium phase-transfer catalysts.