Photoexcited nitroarene-enabled carbon chain-elongated oxidation of alkenes via tandem oxidative cleavage and dipolar cycloaddition

Abstract

Oxidation of alkenes with O₃ and photoexcited nitroarenes represents one of the most attractive organic chemical transformations for the synthesis of oxygen-enriched molecules. However, known achievements are mainly limited to carbon chain-shortened oxidation and carbon chain-retained oxidation of alkenes. Given that constructing higher molecular complexity is the core goal of modern synthesis, the development of chain-elongated oxidation of alkenes would be in high demand but still remains an elusive challenge so far. Herein, we report a photoexcited nitroarene-enabled highly regioselective chain-elongated oxidation of alkenes via tandem oxidative cleavage and dipolar cycloaddition, providing a broad range of synthetically-useful isoxazolidines in up to 92% yield from readily available enol ethers or styrene and derivatives under simple and mild conditions.

Fig. 1. Oxidation of alkenes with ozone or photoexcited nitroarenes.

a Two main types of oxidation of alkenes. b Three possible pathways for oxidation of alkenes by O₃ and photoexcited nitroarenes: carbon chain-shortened oxidation via oxidative cleavage of alkenes (path i, known); carbon chain-retained oxidation via vicinal dihydroxylation (path ii, known); carbon chain-elongated oxidation (path iii, unknown). c This work: photoexcited nitroarene-enabled carbon chain-elongated oxidation via tandem oxidative cleavage and dipolar cycloaddition.

Fig. 2. Reaction development.

a Reaction proposal: the interception of 1,3-dipole with polar C = O will lead to typical ozonolysis, while the interception of 1,3-dipole with nonpolar C = C will give carbon chain-elongated oxidation reaction of alkenes. b Alkene identification. Reaction conditions: S1 (0.2 mmol), R (0.6 mmol), EtOAc (2.0 mL), 8 W 385–390 nm LED, N₂, room temperature, 12 h; yield was determined by ¹H NMR using Cl₂CHCHCl₂ as the internal standard. c Conditions optimization. Optimal conditions: S1 (0.2 mmol), R7 (1.6 mmol), CH₃CN (2.0 mL), 8 W 385–390 nm LED, N₂, room temperature, 12 h; yield was determined by ¹H NMR using Cl₂CHCHCl₂ as the internal standard.

Fig. 3. Scope of nitroarenes.

Reaction conditions: S (0.2 mmol), R7 (1.6 mmol), MeCN (2.0 mL), 8 W 385–390 nm LED, N₂, room temperature, 12 h; yield of isolated products. *16 h.

Fig. 4. Scope of alkenes.

Reaction conditions: S1 (0.2 mmol), R (1.6 mmol), MeCN (2.0 mL), 8 W 385–390 nm LED, N₂, room temperature, 12 h; yield of isolated products.

Fig. 5. Synthetic utility and mechanistic experiments.

a Gram-scale reaction. b Versatile transformations of ethoxyl group of isoxazolidine. c Ring opening of isoxazolidine for 1,3-aminoalcohol. d Radical trapping experiment. e Light on-off experiments. f Intermediate trapping experiment. g Isolated byproduct. h Proposed mechanism. Ar = 3-NO₂-5-CF₃-C₆H₃.