Radical Sorting as a General Framework for Deaminative C(sp3)–C(sp2) Cross-Coupling

Radical-based transition-metal-catalyzed cross-couplings are invaluable tools in synthetic medicinal chemistry. Although carboxylic acids are now routinely used as radical precursors, an equally abundant class of building blocks—aliphatic primary amines—are not typically considered a starting point for radical coupling. We present a general method for deaminative cross-coupling relying on a dual-catalytic system that generates geminate pairs of non-identical alkyl radicals via photosensitization of unsymmetrical 1,2-dialkyldiazenes, then selectively engages the desired radical species in C(sp3)–C(sp2) bond formation. This Ni-mediated ‘radical sorting’ of geminate radical pairs is key in obtaining high yields and avoiding sideproducts. 1,2-dialkyldiazenes are prepared from diverse primary amines, including peptides and pharmaceutical intermediates, using a Sulfur(VI) Fluoride Exchange click linchpin. Mechanistic insights from this work open unique avenues for radical-based synthetic methodologies.