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Directed ? C-H Amination of Alcohols via Radical Relay Chaperones.

ABSTRACT: A radical-mediated strategy for ? C-H amination of alcohols has been developed. This approach employs a radical relay chaperone, which serves as a traceless director that facilitates selective C-H functionalization via 1,5-hydrogen atom transfer (HAT) and enables net incorporation of ammonia at the ? carbon of alcohols. The chaperones presented herein enable direct access to imidate radicals, allowing their first use for H atom abstraction. A streamlined protocol enables rapid conversion of alcohols to their ?-amino analogs (via in situ conversion of alcohols to imidates, directed C-H amination, and hydrolysis to NH2). Mechanistic experiments indicate HAT is rate-limiting, whereas intramolecular amination is product- and stereo-determining.

SUBMITTER: Wappes EA

PROVIDER: S-EPMC5940001 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Directed β C-H Amination of Alcohols via Radical Relay Chaperones.

Wappes Ethan A EA Nakafuku Kohki M KM Nagib David A DA

Journal of the American Chemical Society 20170725 30

A radical-mediated strategy for β C-H amination of alcohols has been developed. This approach employs a radical relay chaperone, which serves as a traceless director that facilitates selective C-H functionalization via 1,5-hydrogen atom transfer (HAT) and enables net incorporation of ammonia at the β carbon of alcohols. The chaperones presented herein enable direct access to imidate radicals, allowing their first use for H atom abstraction. A streamlined protocol enables rapid conversion of alco ...[more]

PMID: 28741940

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