PhI(OAc)2-Mediated One-Pot Oxidative [3+2] Cycloaddition/ Heterocyclization Reactions of Aldoximes with N-Arylmaleimides: A Facile Access to N-Substituted Pyrrolo-Isoxazoles

A convenient and efficient metal-free oxidative [3+2] cycloaddition reaction of N-arylmaleimides with nitrile oxides generated in situ from the corresponding aldoximes using diacetoxyiodobenzene (DIB) as hypervalent iodine reagent under mild conditions has been established. The one-pot oxidative cycloaddition afforded corresponding bioinspired bicyclic isoxazole/pyrrolo-isoxazole derivatives in up to 91 % yield at room temperature. To demonstrate the efficacy of this methodology, the reaction was scaled up to the gram-scale showing synthetic potential in industrial application. The one-pot fashion makes the strategy highly time-economic, atom-economic and minimizes chemical waste by circumventing several purification steps.

Automated summary

A convenient and efficient metal-free oxidative [3+2] cycloaddition reaction has been developed using diacetoxyiodobenzene (DIB) as a hypervalent iodine reagent. N-arylmaleimides react with nitrile oxides generated in situ from the corresponding aldoximes, affording bioinspired bicyclic isoxazole/pyrrolo-isoxazole derivatives in high yields. The one-pot synthesis strategy demonstrated its potential in industrial application by scaling up the reaction to the gram-scale.