Organocatalytic Synthesis of Amides Using Thioacids and Anilines via Electron Donor-Acceptor Photoactivation

Amides are important structures with relevance in biology, material science, and synthetic chemistry. Their photochemical synthesis via aminolysis of acetyldisulfides relies on a reductive regime of thioacids using transition metal-based photocatalysts and organic dyes. Here, we report that readily available tetrachlorophthalimide can serve as an organocatalytic acceptor to thioacids for the electron donor-acceptor (EDA) photoactivation, thereby generating the desired thioacyl radicals suitable for dimerization and, subsequently, amidation via aminolysis. The usefulness of this EDA platform enabled us to develop and demonstrate a mechanistically distinct synthesis of sterically and electronically diverse amides using thioacids as acyl sources, with isolated yields of up to 97%. Furthermore, the reactions proved to be efficient and easy to operate as they could be conducted under an open-air atmosphere, eliminating the need to create a rigorous inert atmosphere. Notably, the gram-scale synthesis of paracetamol was achieved using the developed photochemical transformation.