Development of a New Radical-mediated Pathway for Ketone Synthesis Using Thioesters as Starting Materials



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There has been a great interest in synthesizing ketones in the presence of different functional groups such as in natural product synthesis. This research project aims to develop a new approach to the convergent ketone synthesis via utilizing radical species as nucleophiles. Radical addition to carbonyls produces high-energy alkoxy radicals and renders the first step of this process highly endergonic. Furthermore, the reverse process of ejecting the radical (β-scission) is often the most favorable decomposition pathway, regenerating the carbonyl starting material. The presence of a thioester-derived oxy radical in alkoxy radical can lower the activation barrier for the desired βscission and cleavage of C-S bond, hence thioesters has chosen as coupling partners. This is considered to be as a result of thiyl radical’s stability. The specific aims are to employ intermolecular and intramolecular reactions to synthesize ketone product via using thioesters as starting materials. In intermolecular approach, the photocatalysis associated radical generation method was employed to synthesize ketone via an intermolecular reaction. This specific Aim is centered on the intermolecular addition of nucleophilic radicals to different thioesters. In intramolecular approach, a chain containing both coupling partners is employed. This aim leverages this concept via utilizing AIBN/Bu3SnH, AIBN/(TMS)3SiH and Et3B/O2 as radical initiators. Nevertheless, we did not get any fortune to see any desired ketone product for the photocatalysis utilized intermolecular approach. In most cases, we were able to observe N-Bocpyrrolidine, benzoic anhydride and thiol as byproducts. Formation of byproducts suggested the need of additional energy to decrease the energy barrier between the starting materials and oxy radical and that can be obtained through increasing the nucleophilicity of the D-amino radical and supplying heat to the reaction mixture. Care should be taken to avoid reaction between thioester in the presence of the photocatalyst in order to generate the end ketone product. The successful development of this project would provide a new methodology to access ketones and expand the organic chemist’s toolbox.



Ketones, Esters, Radicals (Chemistry), Oxygen