Bifunctional Iminophosphorane Organocatalysts for Enantioselective Synthesis: Application to the Ketimine Nitro-Mannich Reaction

The design, synthesis, and development of a new class of modular, strongly basic, and tunable bifunctional Bronsted base/H-bond-donor organocatalysts are reported. These catalysts incorporate a triaryliminophosphorane as the Bronsted basic moiety and are readily synthesized via a last step Staudinger reaction of a chiral organoazide and a triarylphosphine. Their application to the first general enantioselective organocatalytic nitro-Mannich reaction of nitromethane to unactivated ketone-derived imines allows the enantioselective construction of beta-nitroamines possessing a fully substituted carbon atom. The reaction is amenable to multigram scale-up, and the products are useful for the synthesis of enantiopure 1,2-diamine and alpha-amino acid derivatives.