New Synthetic Approach to Nitrogen-containing Heterocycles based on Nitrene Species Generated from Cyclic Oxime Esters

Unsaturated valence-six reactive intermediates such as carbenes and nitrenes have long served as fundamental building blocks in organic synthesis. Our research group has focused on developing efficient strategies for generating organometallic species derived from these intermediates and exploiting their reactivities in catalytic organic synthesis. The present article exclusively summarizes our studies on nitrene-based transformations. We initiated our nitrene research by conceptualizing a mechanistic hypothesis in which the release of ring strain from nitrene surrogates could be combined with metal-mediated N-O bond cleavage followed by decarboxylation of isoxazol-5(4H)-ones (isoxazolone) as versatile nitrene precursors. These precursors have enabled a series of transition-metal-catalyzed transformations that lead to diverse nitrogen-containing molecules. By judicious choice of metal catalysts, we have established general and modular routes to a wide range of valuable N-heterocycles and functionalized nitrogen-based frameworks. This account emphasizes the power of rational precursor design in nitrene chemistry and demonstrates how transition-metal catalysts can precisely control pathways of reactive intermediates. We believe that the precursor strategy outlined here will continue to inspire new methodologies for the catalytic synthesis of nitrogen-containing compounds.