Visible-Light-Mediated Selective Allylic C–H Oxygenation of Cycloalkenes

Abstract

A visible-light-mediated selective allylic C–H bond oxygenation of cyclic olefins is presented. Hence, the selective, mild monooxygenation of simple cycloalkenes has been achieved using an acridinium photoredox catalyst in combination with a phosphate base and a disulfide HAT reagent under air atmosphere at room temperature. The combination of both photocatalyst and HAT reagent, which can operate through a single or two different concurrent mechanistic pathways for the formation of the allyl radical, proved highly efficient, while the reaction with exclusively one or the other mediator performs in significantly lower yields. The formed allyl radical further reacts with a molecule of oxygen to build the corresponding peroxyradical that can abstract a hydrogen atom of another cycloalkene substrate, generating the known hydroperoxide intermediate in the formation of the ketone moiety. The advantages of this method rely on the easy use of air as oxygen source, as well as the selective monooxygenation of cycloalkenes without substitution in one of the allylic positions. Besides simple cyclic olefins, the method was also successfully applied in the oxidation of natural products such as the terpene valencene or cholesterol derivatives.

Key words

photocatalysis - allylic oxidation - C–H oxygenation - acridinium salts - visible light

Publication History

Received: 03 October 2023

Accepted after revision: 29 November 2023

Accepted Manuscript online:
29 November 2023

Article published online:
05 January 2024

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• 14 General Procedure for the Allylic Oxidation Reaction of 1 A photovial was equipped with a small stirring bar (1.0 cm × 0.6 cm × 0.6 cm), cyclohexene (1, 10.1 μL, 0.10 mmol, 1.0 equiv), the HAT-II reagent (30.8 mg, 0.10 mmol, 1.0 equiv.), the base (n-Bu₃MeN)O₂P(On-Bu)₂ (41.0 mg, 0.10 mmol, 1.0 equiv), photocatalyst PC-I (4.1 mg, 0.01 mmol, 10 mol%), and 1 mL of dry DCE. The reaction was stirred (700 rpm) open to air (through a needle) for 18 h in a photoreactor under 455 nm irradiation. The yield was determined by GC analysis using 2-methylnaphtalene or n-hexadecane as an internal standard or by NMR analysis using CH₂Br₂ as internal standard. The product was isolated by silica gel column chromatography using pentane/Et₂O (4:1) as eluent, leading to cyclohexenone (2) as a colorless oil (13.2 mg, 0.137 mmol, 69%). ¹H NMR (400 MHz, CDCl₃): δ = 6.99 (dt, J = 10.2, 4.1 Hz, 1 H), 6.02 (dt, J = 10.2, 2.1 Hz, 1 H), 2.48–2.40 (m, 2 H), 2.35 (tdd, J = 6.2, 4.1, 2.1 Hz, 2 H), 2.02 (dq, J = 8.1, 6.1 Hz, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 199.9, 150.7, 130.1, 38.3, 25.8, 22.9 ppm.
• 15 In some reactions, negligible quantity of unidentified insoluble residues was formed during the reaction, indicating partial polymerization. This was, however, more pronounced and visible for the reaction of 5.