Synthesis of Aldehydes through the Iron-Mediated Tsuji–Wacker Oxidation of Olefins

Keywords

iron catalysis - olefins - anti-Markovnikov - Tsuji–Wacker oxidation - aldehydes - photoredox

Significance

The Tsuji–Wacker oxidation of readily available olefins enables access to carbonyl compounds, though under conventional conditions typically leads to the ketone from oxidation occurring predominantly at the more-substituted carbon. While methods have been developed to direct oxidation to the less-substituted carbon (anti-Markovnikov (AM) selectivity) to generate aldehydes, these often involve directing groups, designer catalyst systems or intermediacy of an epoxide, and are therefore limited in scope. The use of photoexcited nitroarenes as oxygen-transfer reagents to alkenes is well documented, and the current report describes the Fe-mediated biased fragmentation of the intermediate 1,3,2-dioxazoline intermediate to generate selectively the aldehyde product.

Comment

Optimization studies demonstrated that addition of the Lewis acid at low temperature to the irradiated reaction mixture of the electron-deficient nitroarene and the olefin enabled suppression of the typical oxidative cleavage that occurs through retrocycloaddition, and instead led to fragmentation to provide the oxidation product with exclusive AM selectivity. In some cases, the product was isolated as the acetal owing to volatility of the corresponding aldehyde (5, 6). The reaction showed a broad substrate scope with good functional group tolerance, though was incompatible with substrates containing strongly Lewis basic groups. Mechanistic studies suggest that the reaction proceeds through a carbocation intermediate that undergoes a 1,2-hydride shift while utilization of acetone as a co-solvent led to the development of a protocol for the synthesis of acetonides.

Publication History

Article published online:
22 May 2025