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Hydroxy-directed fluorination of remote unactivated C(sp³)-H bonds: a new age of diastereoselective radical fluorination.

ABSTRACT: We report a photochemically induced, hydroxy-directed fluorination that addresses the prevailing challenge of high diastereoselectivity in this burgeoning field. Numerous simple and complex motifs showcase a spectrum of regio- and stereochemical outcomes based on the configuration of the hydroxy group. Notable examples include a long-sought switch in the selectivity of the refractory sclareolide core, an override of benzylic fluorination, and a rare case of 3,3'-difluorination. Furthermore, calculations illuminate a low barrier transition state for fluorination, supporting our notion that alcohols are engaged in coordinated reagent direction. A hydrogen bonding interaction between the innate hydroxy directing group and fluorine is also highlighted for several substrates with ¹⁹F-¹H HOESY experiments, calculations, and more.

SUBMITTER: Harry SA

PROVIDER: S-EPMC9200124 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Hydroxy-directed fluorination of remote unactivated C(sp3)-H bonds: a new age of diastereoselective radical fluorination.

Harry Stefan Andrew SA Xiang Michael Richard MR Holt Eric E Zhu Andrea A Ghorbani Fereshte F Patel Dhaval D Lectka Thomas T

Chemical science 20220530 23

We report a photochemically induced, hydroxy-directed fluorination that addresses the prevailing challenge of high diastereoselectivity in this burgeoning field. Numerous simple and complex motifs showcase a spectrum of regio- and stereochemical outcomes based on the configuration of the hydroxy group. Notable examples include a long-sought switch in the selectivity of the refractory sclareolide core, an override of benzylic fluorination, and a rare case of 3,3'-difluorination. Furthermore, calc ...[more]

PMID: 35774162

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