Organocatalytic C-H Hydroxylation

Key words

C-H hydroxylation - oxaziridines - hydrogen peroxide - hydrophobic aggregation

Significance

Based on the authors’ previous work in this field (J. Am. Chem. Soc. 2005, 127, 15391) a second-generation oxaziridine 2-mediated catalytic process for C-H hydroxylation is reported. The revised reaction protocol features the use of aqueous H₂O₂ in AcOH-H₂O (1:1), conditions which efficiently generate the reactive oxaziridine intermediate 2 in situ from the benzoxa­thiazine catalyst 1. Among all catalysts 1 tested, catalyst 1e (R = C₆F₅) turned out to be the most effective suggesting hydrophobic catalyst-substrate aggregation as proposed by the authors. Mechanistically, oxaziridine-mediated electrophilic O-atom insertion into C-H bonds likely proceeds in a concerted, asynchronous fashion.

Comment

Most catalytic C-H bond hydroxyl­ation processes rely on transition metal complexes to support reactive metal-oxo or metal-peroxo species (for an example, see: M. S. Chen, M. C. White Science 2007, 318, 783). Curci and co-workers have used dioxiranes - strained, electrophilic heterocycles - for the oxygenation of saturated hydrocarbons (Acc. Chem. Res. 2006, 39, 1). In contrast the Du Bois group employs in situ generated oxaziridines 2 for the same purpose. Compared to their first-generation process the advanced method not only simplifies the experimental protocol by avoiding Ar₂Se₂ as co-catalyst but also has a significantly broader substrate scope.