Phenothiazine Sulfoxides as Active Photocatalysts for the Synthesis of γ-Lactones

Hölter N.; Rendel N.H.; Spierling L.; Kwiatkowski A.; Kleinmans R.; Daniliuc C.G.; Wenger O.S.; Glorius F.

Abstract

N-substituted phenothiazines are prominent and highly effective organic photoredox catalysts, particularly known for their strong reducing capabilities. Despite their wide utility, the closely related phenothiazine sulfoxides, which easily form upon oxidation, have been largely overlooked and have not been explored in the context of photocatalysis. Herein, we describe the discovery and application of N-phenylphenothiazine sulfoxide as a photocatalyst for the reductive activation of cyclic malonyl peroxides, giving access to complex γ-lactones starting from simple olefins. Detailed mechanistic studies were carried out to better understand the in situ formation of the active catalyst species from a commercial precursor, as well as the catalyst species interconversion and the photocatalytic mechanism for the formation of γ-lactone products. Specifically, we employed a broad range of mechanistic tools, including time-resolved spectroscopy, spectroelectrochemistry, transient UV-vis absorption spectroscopy, cyclic voltammetry, isotopic labeling, radical trapping experiments, NMR spectroscopy, and density functional theory (DFT) calculations. The synthetic utility of this protocol is demonstrated in a substrate scope study, highlighting the facile access to complex spirocyclic γ-lactones, which are widely recognized for their biological importance.