A selective, remote desaturation has been developed to rapidly access homoallyl amines from their aliphatic precursors. The strategy employs a triple H-atom transfer (HAT) cascade, entailing (i) cobalt-catalyzed metal-HAT (MHAT), (ii) carbon-to-carbon 1,6-HAT, and (iii) Co–H regeneration via MHAT. A new class of sulfonyl radical chaperone (to rapidly access and direct remote, radical reactivity) enables remote desaturation of diverse amines, amino acids, and peptides with excellent site-, chemo-, and regioselectivity. The key, enabling C-to-C HAT step in this cascade was computationally designed to satisfy both thermodynamic (bond strength) and kinetic (polarity) requirements, and it has been probed via regioselectivity, isomerization, and competition experiments. We have also interrupted this radical transfer dehydrogenation to achieve γ-selective C–Cl, C–CN, and C–N bond formations.

A radical aza-Heck cyclization has been developed to afford functionally rich products with four contiguous C-heteroatom bonds. This multicatalytic strategy provides rapid syntheses of dense, medicinally relevant motifs by enabling the conversion of alcohol-derived imidates to heteroatom-rich fragments containing vinyl oxazolines/oxazoles, allyl amines, β-amino alcohols/halides, and combinations thereof. Mechanistic insights of this process show how three distinct photocatalytic cycles cooperate to enable: (1) imidate radical generation by energy transfer, (2) dehydrogenation by Co catalysis, and (3) catalyst turnover by electron transfer.

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