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. 2016 Mar 1;7(3):1904-1909.
doi: 10.1039/c5sc04476f. Epub 2015 Nov 27.

Chemo- and regioselective oxygenation of C(sp3)-H bonds in aliphatic alcohols using a covalently bound directing activator and atmospheric oxygen

Jun Ozawa  1 , Masayuki Tashiro  1 , Jizhi Ni  1   2 , Kounosuke Oisaki  1 , Motomu Kanai  1   2
Affiliations

Chemo- and regioselective oxygenation of C(sp3)-H bonds in aliphatic alcohols using a covalently bound directing activator and atmospheric oxygen

Jun Ozawa et al. Chem Sci. .

Abstract

Chemically reactive directing groups (directing activators) represent a promising strategy for mild and regioselective C(sp3)-H functionalization. The use of a radical N-oxyl directing activator promoted the aerobic oxygenation of benzylic, propargylic, tertiary, and unactivated acyclic methylene C(sp3)-H bonds in aliphatic alcohols with γ- (or δ-) selectivity under mild conditions (room temperature to 50 °C). The reaction was unaffected by the presence of various oxidation-sensitive functional groups, which proved to be problematic in previously reported studies on the oxidation of C(sp3)-H bonds. Structural modifications on the directing activator altered the regioselectivity, and thus provided an ultra-remote aerobic C(sp3)-H oxygenation. The observed reactivity and regioselectivity could be rationalized in terms of the intramolecular conformational accessibility of the N-oxyl radical and the electronic characteristics of C(sp3)-H bonds.

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Figures

Scheme 1
Scheme 1. Chemo- and regioselective intramolecular oxidation of C(sp3)–H bonds in aliphatic alcohols using a novel directing activator.
Scheme 2
Scheme 2. Undesired C–C bond cleavage of 1ivia decomposition of hydroperoxide intermediate.
Scheme 3
Scheme 3. Selective ultra-remote aerobic C–H oxygenation. a 1 mol% Co(OAc)2 and 2.2 equiv. of Me2S were added at 0 h and 1.5 h. b Isolated yield is described and yield in parenthesis was calculated from the 1H NMR spectra of the crude mixture using 1,1,2,2-tetrachloroethane as an internal standard.
Scheme 4
Scheme 4. Confirmation of an intramolecular reaction mechanism. a 1 mol% Co(OAc)2 and 2.2 equiv. of Me2S were added at 0 h and 1.5 h. b The yield was calculated from the 1H NMR spectra of the crude mixture using 1,1,2,2-tetrachloroethane as an internal standard.
Scheme 5
Scheme 5. Plausible reaction mechanism.
See this image and copyright information in PMC

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