Late-Stage Oxidation of C(sp3)─H Bonds with High Efficiency and Alkyl Group Dihydroxylation of Complex Molecules

Kang, Yi Cheng; Volochnyuk, Dmitriy M.; Ryabukhin, Serhiy V.; Hartwig, John F.

doi:10.1002/ange.202513418

Late-Stage Oxidation of C(sp³)─H Bonds with High Efficiency and Alkyl Group Dihydroxylation of Complex Molecules

Journal Article · Tue Sep 23 00:00:00 EDT 2025 · Angewandte Chemie

DOI:https://doi.org/10.1002/ange.202513418· OSTI ID:3014692

^[1]; Volochnyuk, Dmitriy M. ^[2]; Ryabukhin, Serhiy V. ^[2]; ^[1]

University of California, Berkeley, CA (United States)
Taras Shevchenko National University of Kyiv (Ukraine); NAS of Ukraine, Kyiv (Ukraine)

Here, the late-stage oxidation of C(sp³)─H bonds is highly valuable for modulating the solubility and binding of bioactive compounds and for diversification of complex molecules. Undirected methods for C(sp³)─H oxidation are valuable for the installation of hydroxyl groups at sites remote from other functional groups present in the molecule, but existing catalysts are limited by low turnover numbers and lengthy ligand syntheses. Perfluorinated ruthenium porphyrins are highly active catalysts for the oxidation of alkyl C─H bonds, but the scope of the transformation with complex molecules under conditions of limiting substrate has not been investigated. We report that carbonylruthenium(II) tetrakis(pentafluorophenyl)porphyrin [Ru(TPFPP)(CO)] catalyzes the selective oxidation of tertiary C(sp³)─H bonds in a broad range of complex natural products and drugs, with turnover numbers as high as 1000, and the tolerance of the reaction to various functional groups was rapidly assessed by performing a model reaction in the presence of additives. We show how the combination of this undirected C(sp³)─H oxidation and a directed C(sp³)─H silylation and oxidation provides rapid access to highly oxidized, 1,2-diol derivatives of natural products by a formal dihydroxylation of an alkyl group.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division (CSGB)

Grant/Contract Number:: AC02-05CH11231

Other Award/Contract Number:: R35GM130387
S10OD024998

OSTI ID:: 3014692

Journal Information:: Angewandte Chemie, Journal Name: Angewandte Chemie Journal Issue: 46 Vol. 137; ISSN 1521-3757; ISSN 0044-8249

Publisher:: German Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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