biostudies-literaturePrusinowski AFDivision of ChemistryNCRR NIH HHSNational Institute of General Medical SciencesNIGMS NIH HHS5429-5438https://www.ebi.ac.uk/biostudies/studies/S-EPMC7299201biostudies-literatureUnknown142(11)A double functionalization of <i>vicinal sp</i>³ C-H bonds has been developed, wherein a β 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 β alkene that is amino-iodinated in situ. Overall, the radical-polar-crossover cascade entails the following key steps: (i) β C-H iodination via 1,5-hydrogen atom transfer (HAT), (ii) desaturation via I₂ complexation, and (iii) <i>vicinal</i> 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,β,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.Journal of the American Chemical Society<i>Vicinal</i>, Double C-H Functionalization of Alcohols via an Imidate Radical-Polar Crossover Cascade.PMC7299201S10 RR027172CAREER 1654656R35 GM119812Prusinowski AFWappes EATwumasi RKNagib DAfalse<i>Vicinal</i>, Double C-H Functionalization of Alcohols via an Imidate Radical-Polar Crossover Cascade.A double functionalization of <i>vicinal sp</i>³ C-H bonds has been developed, wherein a β 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 β alkene that is amino-iodinated in situ. Overall, the radical-polar-crossover cascade entails the following key steps: (i) β C-H iodination via 1,5-hydrogen atom transfer (HAT), (ii) desaturation via I₂ complexation, and (iii) <i>vicinal</i> 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,β,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.2020-01-01T00:00:00Z2020 Mar2025-04-04T01:45:56.157Z2025-04-04T01:45:56.157ZS-EPMC72992013214174110.1021/jacs.0c01318