Applications of Homogeneous and Heterogeneous Photocatalysts for Late-Stage Transformations of Organic Molecules

Promovendus/a: Prakash Kumar Sahoo

Promotor(en): Shoubnik Das, Bert Maes

The employment of costly, single-use catalysts, highly toxic reagents/reactants, and solvents is still a major problem within synthetic chemistry. Therefore, it becomes difficult for pharma industries to reduce the price as well as environmental toxicity. In this regard, ample attention needs to be given to the chemical community to replace them with inexpensive, abundant, benign, and reusable substitutes. The goal of this doctoral thesis was to contribute towards the sustainable development of novel synthetic methodologies for the synthesis and functionalization of pharmaceutical molecules and natural products using metal-free homogeneous and sustainable, single-atom-doped heterogeneous photocatalysis.

The research described in this thesis can be divided into four chapters. In the first chapter, we have shown the development of a robust, cost- and energy-efficient strategy to introduce diverse nucleophiles, including alcohols, carboxylic acids, and amines, via the functionalization of benzylic C−H bonds of simple aromatic building blocks as well as complex drug molecules and natural products. The second chapter demonstrates a redox-neutral decarboxylative radical polar crossover process for the synthesis of linear aliphatic amines using 4CzIPN as an organo-photocatalyst. The synthetic utility of this method is further demonstrated by the late-stage functionalization of pharmaceuticals as well as the synthesis of drug compounds. In the third chapter, a Mn metal-doped g-c3n4 heterogeneous photocatalyst has been developed to achieve the vicinal dichlorination of alkenes using N-Chlorosuccinamide as a chlorinating agent. Noteworthily, both unactivated and activated alkenes provide good to excellent yields with mild reaction conditions. Interestingly, nine pharmaceutical compounds have been functionalized with our system to prove the synthetic applicability of our method. Finally, the fourth chapter demonstrates a Mn metal-doped heterogeneous photocatalytic method for the selective para-chlorination of alkenes using N-chlorosuccinamide as a chlorinating agent. Mostly electron-rich aromatics worked in this system.

Overall, the thesis contributes to the pharmaceutical industry by developing different methodologies that can selectively functionalize specific positions of complex pharmaceutical molecules with functional groups like amine, ether, ester, and chlorine in the presence of both homogeneous and single-metal-atom-doped heterogeneous photocatalysts using a mild photo-redox system. ​ ​