Executive Summary : | Synthesis of fine chemicals and APIs are among the highest Environmental (E) factor (waste/product) of 25-100. Amide bond formation is one of the most frequently used reactions via the condensation of a carboxylic acid with an amine with considerable waste generation. With climate change and environmental footprints of the chemical and pharmaceutical industry is in the focus, direct and diverse functionalization of feedstock chemicals becoming increasingly important. Harvesting solar energy could lead to the activation of stable organic molecules to their reactive excited state. The use of aerobic oxygen as an oxidant is the quintessence of sustainability as nature uses oxygen for all oxidation. The visible light absorption triggers an electronic transition to initiate the single-electron process (radical chemistry). The radical (open-shell) reactivity is complementary to that of classical ionic chemistry, leading to functionalization not achievable via polar chemistry. The organic radicals are also capable to interact with aerobic triplet oxygen, leading to the possibility of aerobic oxidation under transition metal free conditions. The use of flow chemistry and mechanochemistry are the new verticals for the chemical industry for selective product formation under mild and safe conditions with less waste generation. Hence, a combination of visible light harvesting for energy, aerobic oxygen for oxidation, and establishing the method in flow would significantly improve the efficiencies of amide bond formation. We established phosphite catalysis to control the radical reactions during our sp2 C–H functionalization of carbon-heteroatom double bonds. We recently developed organophosphites as sustainable catalysis to add to the N-heteroaromatic salts and cyclic iminium salts to facilitate a catalyst-bound radical intermediate formation and its strong base mediated rearrangements and aerobic auto-oxidation.In this proposed research, we will explore the aerobic oxidative condensation of aldehydes and amines for coupling reagent free amide synthesis under visible light activation. Aldehydes are inexpensive feedstock chemicals and becoming abundantly available via biomass valorization, making it an attractive alternative starting material for (poly)amide synthesis. Our proposed approach with a “catalyst bound radical intermediate’’ has the potential for chiral atroposelective amide synthesis as well as chiral amides from racemic aldehydes and amine via kinetic or dynamic resolution. The reversibility of aldehyde and amine condensation to imine or iminium could be exploited for the selective formation of macrocyclic imine/iminium to the corresponding amides. |