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, aliphatic primary amines-an equally abundant class of building blocks-are less commonly used in 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 side products. This approach capitalizes on the versatility of the Sulfur(VI) Fluoride Exchange (SuFEx) click reaction combined with the aza-Ramberg-Bäcklund reaction and enables the functionalization of a broad array of structurally diverse primary amines-including peptide derivatives and synthetic pharmaceutical intermediates. Mechanistic insights from this work open unique avenues for radical-based cross-couplings.