Photocatalytic Minisci Reaction

Abstract “Minisci reaction,” the substitution of protonated heteroaromatic bases by nucleophilic carbon-centered radicals, is a versatile organic transformation particularly suited for medicinal and biological applications, due to the large variety of radical sources, the high chemoselectivity, and the simple experimental conditions. This chapter discusses on a photochemical approach with a potential high added value from an eco-friendly point of view. A few years ago, we proposed a sunlight-induced nucleophilic radical addition to protonated heteroaromatic bases, catalyzed by TiO 2 . This protocol was successfully applied to a wide range of radical sources. In a recent paper, Albini and coworkers compared our methodology with a classical thermal Minisci reaction procedure, by means of two methods, the Life Cycle Assessment and the Environmental Assessment Tool for Organic Synthesis, in order to verify the effective eco-friendly impact of the photocatalytic approach. They evidenced a few limitations of our system. However, the study was based on nonoptimized experiments, and moreover the good yield and simplicity of the photocatalytic method were recognized promising by the same authors, and were positively evaluated by a third assessment, EcoScale. In order to improve efficiency of the photochemical protocol and to overcome potential limitations, we have recently conducted preliminary molecular dynamic studies finalized to the future design of ideal TiO 2 crystals.