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Vicinal, Double C–H Functionalization of Alcohols via an Imidate Radical-Polar Crossover Cascade

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journal contribution
posted on 05.03.2020 by Allen F. Prusinowski, Raymond K. Twumasi, Ethan A. Wappes, David A. Nagib
A double functionalization of vicinal sp3 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) 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,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.

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