Executive Summary : | Spirocyclic scaffolds have drawn the immense interest of researchers in recent years owing to their ubiquity in natural products and have been reported to exhibit various biological properties. As a result, they hold considerable promise as structural leads in drug discovery programmes. Despite this, significant limitations exist in current synthetic approaches to these important scaffolds, and therefore, there is a very high demand for more efficient and environmentally friendly methods for their synthesis. Ring strain in organic molecules is a powerful driving force that promotes reactivity through strain-release, allowing the facile construction of a myriad of complex and biologically relevant molecules via ring-opening or ring-expansion strategies. The proposed project aims at developing novel strain-enabled Truce-Smiles rearrangements under visible light photocatalysis to rapidly construct medicinally relevant spiro-fused oxindoles. The strategy will be extended to the synthesis of spirobicyclo[1.1.1]pentanes (spiro-BCPs) derivatives, which are of high importance in the pharmaceutical industry and materials chemistry. Furthermore, we plan to develop strain--enabled radical cascades involving ring-expansion followed by Truce-Smiles rearrangement to synthesize highly functionalized spirooxindoles. Due to the different optical and biological properties of enantiomers, the synthesis of enantioenriched chiral motifs has been a very active and significant field of research in organic synthesis for decades. Thus, in the last part of the proposal, we plan to develop an enantioselective synthesis of functionalized spiro-fused oxindoles. The novel methodologies proposed herein not only benefit from the formation of highly functionalized spirocycles but also lay solid foundations for the development of other strain-enabled reactions. |