A new amide synthesis strategy based on a fundamental mechanistic revision of the reaction of thio acids and organic azides is presented. The data demonstrate that amines are not formed as intermediates in this reaction. Alternative mechanisms proceeding through a thiatriazoline intermediate are suggested. The reaction has been applied to the preparation of simple and architecturally complex amides that are difficult to access using conventional methods. The reaction is chemoselective, effective for unprotected substrates, and compatible with aprotic and protic solvents, including water.

A one-pot procedure for the conversion of carboxylic acids to N-acyl sulfonamides, via thio acid/azide amidation, is presented. The method is compatible with acid- and base-sensitive amino acid protection. N-Acyl sulfonamide synthesis on solid support, peptide thio acid/sulfonazide coupling, and N-alkyl amide synthesis via selective cleavage of sulfonyl from an N-alkyl-N-acyl sulfonamide are also reported.

Disclosed herein is the design of an unprecedented electrophilic rhodium enalcarbenoid which results from rhodium(II)-catalyzed decomposition of a new class of enaldiazo compounds. The synthetic utility of these enalcarbenoids has been successfully demonstrated in the first transition-metal-catalyzed [4+2] benzannulation of pyrroles, thus leading to substituted indoles. The new benzannulation has been applied to the efficient synthesis of the natural product leiocarpone as well as a potent adipocyte fatty-acid binding protein inhibitor.

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A dirhodium carboxylate catalyzed [1+1+3] annulation reaction of diazoenals and vinyl azides that gives synthetically important enal-functionalized 1-pyrroline derivatives was developed. The reaction involves a novel rhodium-catalyzed olefination of diazoenals with vinyl azides via electrophilic enal carbenoids, resulting in a new class of enal acrylates. The annulation reaction was used for the direct synthesis of valuable deuterated 1-pyrrolines. Structural diversification of the enal-functionalized 1-pyrrolines resulted in the biologically important pyrrolidine-fused oxaziridine, amino acid derivatives, and a 6-azabicyclo[3.2.1]octane motif present in polycyclic alkaloids.