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CC BY 4.0 · SynOpen 2024; 08(02): 125-129
DOI: 10.1055/s-0040-1720118
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Oxidative C–N Bond Formation of Isochromans Using an Electronically Tuned Nitroxyl Radical as Catalyst

Kyoko Yano
a   Laboratory of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Yamashinaku, Kyoto 607-8412, Japan
,
Ayano Ohshimo
a   Laboratory of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Yamashinaku, Kyoto 607-8412, Japan
,
Elghareeb E. Elboray
a   Laboratory of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Yamashinaku, Kyoto 607-8412, Japan
b   Department of Chemistry, Faculty of Science, South Valley University, Qena 83523, Egypt
,
Yusuke Kobayashi
a   Laboratory of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Yamashinaku, Kyoto 607-8412, Japan
,
Takumi Furuta
a   Laboratory of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Yamashinaku, Kyoto 607-8412, Japan
,
Shohei Hamada  ∗
a   Laboratory of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Yamashinaku, Kyoto 607-8412, Japan
› Author AffiliationsThis study was supported by Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT KAKENHI) grants 19K16327 and 21K06487 (to S.H.).
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Abstract

The cross-dehydrogenative coupling between isochromans and nucleophiles using an electronically tuned nitroxyl radical catalyst, which effectively promotes the oxidation of benzylic ethers, has been investigated. Using sulfonamides as a nucleophile, modification of isochromans via oxidative C–N bond formation has been achieved at ambient temperature.

Keywords

isochroman - cross-dehydrogenative coupling - nitroxyl radical - C–N bond formation - organocatalyst - oxidation

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1720118.
  • Supporting Information


Publication History

Received: 31 March 2024

Accepted after revision: 24 April 2024

Article published online:
13 May 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by/4.0/)

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  • References and Notes

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  • 17 The hydride-transfer step has already been proposed as the rate-determining step in the oxidation of isochromans to the corresponding oxocarbenium cations; for details, see ref. 4d.
  • 18 General Procedure PIFA (103 mg, 0.240 mmol) was added to a mixture of isochroman (26.8 mg, 200 mmol), 2 (4.6 mg, 20 μmol), K2CO3 (111 mg, 0.800 mmol), and sulfonamide (0.400 mmol) in DCM (2.0 mL). The resulting mixture was stirred under N2 atmosphere for 2 h at room temperature. Then, the reaction was quenched with saturated aq. Na2S2O3 and extracted with CHCl3. Subsequently, the organic layer was dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography.
  • 19 Representative Spectral Data N-(Isochroman-1-yl)-4-methyl­benzenesulfonamide (3)1 The title compound 3 (38.0 mg, 63%) was synthesized from isochroman (26.8 mg, 0.200 mmol) and 4-methylbenzenesulfonamide (68.5 mg, 0.400 mmol). Colorless solid; mp 178–181 °C. 1H NMR (500 MHz, CDCl3): δ = 7.86 (d, J = 8.5 Hz, 2 H), 7.31 (d, J = 7.9 Hz, 2 H), 7.26–7.18 (m, 3 H), 7.08 (d, J = 7.2 Hz, 1 H), 6.10 (d, J = 8.6 Hz, 1 H), 5.40 (d, J = 8.6 Hz, 1 H), 3.73–3.57 (m, 2 H), 2.85 (ddd, J = 15.9, 9.7, 6.0 Hz, 1 H), 2.61 (dt, J = 16.7, 4.0 Hz, 1 H), 2.44 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 143.40, 138.79, 134.54, 132.82, 129.52, 128.87, 128.47, 127.25, 126.84, 126.76, 79.91, 58.76, 27.58, 21.63. IR (ATR) 3202, 1328, 1157, 748 cm–1. HRMS (ESI): m/z [M + Na]+ calcd for C16H17NNaO3S: 326.0827; found: 326.0829.