Regio- and diastereoselective synthesis of cyclobutylated phenothiazines [2 + 2] photocycloaddition: demonstrating wavelength-gated cycloreversion inside live cells.

Herein, we unveiled a regio- and diastereoselective synthesis of cyclobutylated phenothiazines, a unique class of structural congeners of phenothiazines visible-light-irradiated intermolecular [2 + 2]-cycloaddition reaction, from readily available naphthoquinones, 2-aminothiophenols, and styrenes, either in a two-step or three-component coupling process. By varying substitutions in all three coupling partners, a library of cyclobutylated phenothiazines, including late-stage derivatization with five commercial drugs, has been realized with up to 97% isolated yield. In contrast to the reported pathways, the developed [2 + 2]-photocycloaddition seems to proceed a 'photoinduced-electron-transfer' (PET) mechanism, which is well corroborated with the experimental observations, Rehm-Weller equation, and computation studies.