Deaminative Giese-type reaction

Abstract

Primary aliphatic amines are essential components in numerous functional molecules and rank among the most readily available commercial building blocks. Although commonly utilized as nitrogen nucleophiles, their application as alkyl sources for constructing (sp³)C-C(sp³) bonds remains a notable challenge. Here we present an approach integrating nitrogen-atom deletion into the aza-Michael reaction, thereby redirecting the classical pathway from (sp³)C-N bond formation to (sp³)C-C(sp³) bond construction. Leveraging commercially available O-diphenylphosphinylhydroxylamine as an efficient nitrogen-deletion reagent, this method enables a wide variety of primary aliphatic amines to serve as alkyl sources in couplings with structurally diverse electron-deficient olefins. This Giese-type reaction proceeds under mild conditions, achieves completion within 10 min and exhibits broad functional-group compatibility. By bridging two foundational transformations-the aza-Michael reaction and the Giese-type reaction-this approach interlinks their product spaces through a unified precursor library, substantially enhancing synthetic utility.