RESUMEN
A radical aza-Heck cyclization has been developed to afford functionally rich products with four contiguous C-heteroatom bonds. This multi-catalytic 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, ß-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.
RESUMEN
A double functionalization of vicinal sp3 C-H bonds has been developed, wherein a ß amine and γ iodide are incorporated onto an aliphatic alcohol in a single operation. This approach is enabled by an imidate radical chaperone, which selectively affords a transient ß alkene that is amino-iodinated in situ. Overall, the radical-polar-crossover cascade entails the following key steps: (i) ß C-H iodination via 1,5-hydrogen atom transfer (HAT), (ii) desaturation via I2 complexation, and (iii) vicinal amino-iodination of an in situ generated allyl imidate. The synthetic utility of this double C-H functionalization is illustrated by conversion of aliphatic alcohols to a diverse collection of α,ß,γ substituted products bearing heteroatoms on three adjacent carbons. The radical-polar crossover mechanism is supported by various experimental probes, including isotopic labeling, intermediate validation, and kinetic studies.
