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 Brønsted base/H-bond-donor
organocatalysts are reported. These catalysts incorporate a triaryliminophosphorane
as the Brønsted 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 β-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 α-amino acid derivatives.