Mesoionic N-Heterocyclic Imines as Super Nucleophiles in Catalytic Couplings of Amides with CO.

An extended class of stable mesoionic N-heterocyclic imines (mNHIs), containing a highly polarized exocyclic imine moiety, were synthesized. The calculated proton affinities (PA) and experimentally determined Tolman electronic parameters (TEPs) reveal that these synthesized mNHIs have the highest basicity and donor ability among NHIs reported so far. The superior nucleophilicity of newly designed mNHIs was utilized in devising a strategy to incorporate CO as a bridging unit under reductive conditions to couple inert primary amides. This strategy was further extended to hetero-couplings between amide and amine using CO . These hitherto unknown catalytic transformations were introduced in the diversification of various biologically active drug molecules under metal-free conditions. The underlying mechanism was explored by performing a series of control experiments, characterizing key intermediates using spectroscopic and crystallographic techniques.