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. 2017 Oct 1;8(10):7180-7185.
doi: 10.1039/c7sc02773g. Epub 2017 Sep 4.

A unified photoredox-catalysis strategy for C(sp3)-H hydroxylation and amidation using hypervalent iodine

Guo-Xing Li  1 , Cristian A Morales-Rivera  2 , Fang Gao  1 , Yaxin Wang  1 , Gang He  1 , Peng Liu  2 , Gong Chen  1   3
Affiliations

A unified photoredox-catalysis strategy for C(sp3)-H hydroxylation and amidation using hypervalent iodine

Guo-Xing Li et al. Chem Sci. .

Abstract

We report a unified photoredox-catalysis strategy for both hydroxylation and amidation of tertiary and benzylic C-H bonds. Use of hydroxyl perfluorobenziodoxole (PFBl-OH) oxidant is critical for efficient tertiary C-H functionalization, likely due to the enhanced electrophilicity of the benziodoxole radical. Benzylic methylene C-H bonds can be hydroxylated or amidated using unmodified hydroxyl benziodoxole oxidant Bl-OH under similar conditions. An ionic mechanism involving nucleophilic trapping of a carbocation intermediate by H2O or CH3CN cosolvent is presented.

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Figures

Scheme 1
Scheme 1. C(sp3)–H oxygenation and amination with hypervalent iodine(iii).
Scheme 2
Scheme 2. Substrate scope of tertiary C–H hydroxylation with PFBl–OH 17. (a) Isolated yield on 0.2 mmol scale under the standard conditions, c ∼ 50 mM. For reaction with <85% conversion of starting material, yields based on recovered SM (BRSM) were given in braces. (b) H2 18O (97% 18O) was used. (c) 3 mmol scale, 46 h. (d) C3 hydroxylation product <5%. (e) No C3 hydroxylation product was detected. (f) No free OH product was obtained.
Scheme 3
Scheme 3. Substrate scope of benzylic C–H hydroxylation with Bl–OH 13. (a) Isolated yield on a 0.2 mmol scale under standard conditions, c ∼ 45 mM, yield of ketone by-product was given in parentheses. (b) 1.5 equiv. of 13 was used. (c) 4 equiv. of 13 was used. (d) 5 mmol scale, 20 h. (e) H2 18O (97% 18O) was used.
Scheme 4
Scheme 4. C(sp3)–H amidation with 13 or 17. (a) Conditions A for tertiary C–H amidation, HFIP/CH3CN (4/3), c ∼ 30 mM, 24 h; conditions B for benzylic C–H amidation, HFIP/CH3CN (8/3), c ∼ 35 mM, 10 h. Anhydrous HFIP and CH3CN dried over 4 Å molecular sieves were used. Isolated yield on a 0.2 mmol scale. (b) 1 equiv. of cyclohexane was used, 0.5 mmol scale. (c) PhCN was used as cosolvent, HFIP/PhCN (8/5), c ∼ 30 mM, 10 h.
Scheme 5
Scheme 5. Mechanistic consideration of C(sp3)–H functionalization with PFBl–OH. DFT calculations were performed at the M06-2X/6-311++G(d,p)-SDD/SMD(HFIP)//M06-2X/6-31+G(d)-SDD level of theory. All energies are in kcal mol–1. See ESI of DFT calculations with Bl–OH.
See this image and copyright information in PMC

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