C(sp³)–C(sp³) bond formation through nitrogen deletion of secondary amines using O-diphenylphosphinylhydroxylamine

The nitrogen deletion of secondary amines has emerged as an effective strategy for direct molecular skeletal editing and carbon–carbon bond formation. However, current methods are often limited to acyclic bis(α-primary) amines and cyclic amines, which possess two stabilizing elements at the α-position of amine. Here we report the use of O-diphenylphosphinylhydroxylamine as a reagent for nitrogen deletion of secondary amines to form C(sp³)–C(sp³) bonds. This method overcomes substrate requirements of other methods and tolerates a range of secondary amine substrates. The process can be readily applied to multiple nitrogen deletion processes, is tolerant of both air and water, forms water-soluble byproducts and can be readily scaled to a hundred-gram scale. The versatility of the method is further showcased through the direct editing of natural products, pharmaceutical compounds, N-coordinated ligands, a three-dimensional amine cage and the synthesis of several bioactive compounds.