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

doi:10.1021/jacs.0c01318

Paper

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

Published Mar 6, 2020 · Allen F. Prusinowski, Raymond K Twumasi, Ethan A. Wappes

Journal of the American Chemical Society

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Abstract

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.

Study Snapshot

Key takeawayThis study developed a double C-H functionalization method for aliphatic alcohols, enabling the conversion to diverse heteroatom-bearing products in a single operation.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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

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