Research Projects

The ability to selectively edit a molecular framework will offer a new retrosynthetic logic and rapidly increase the compound's overall complexity. In this regard, two main paradigms have evolved—core and peripheral skeletal editing. The former paradigm enables core framework editing without disrupting the appended functionalities, whereas the latter solely alters the molecule's periphery without pruning the compound's core skeleton. Development in both these directions will be immensely fruitful in drug discovery, and consequently, research in this field has received significant attention over the past few years. Chemical transformations that introduce, remove, or manipulate functional groups are ubiquitous in the synthetic chemistry literature. Unlike traditional functional group interconversion involving functionality swap, reactions that alter solely the position of the functional groups are far less explored. This overall protocol will complement the C–H functionalization field, providing an opportunity to functionalize previously inaccessible positions. Showcasing such protocol on saturated carbocycles will be a significant contribution as it alters the system's inherent three-dimensional framework and rapidly adds to the molecular complexity. This proposal explores the concept of remote C–H functionalization by transposing the acyl groups in a 1,3-fashion. Acyl groups typically serve as versatile chemical fragments, considering their ability to be transformed into various functionalities. We relied on a unique strategy of bridging the widely employed Norrish–Yang cyclization, a selective --scission, and a subsequent H-atom transfer to favor a direct positional exchange between an acyl group and an unactivated C–H bond. Notably, the system’s core will remain untouched, and this transformation will be 100% atom-economical. Conceptually, in this transformation, only the acyl group is transposed to a new position, thereby permitting site-selective functionalization without involving a site-selective C–H cleavage step. The synthetic utility of this transformation will eventually be explored in other synthetic settings by varying the parent position of the acyl appendage. Subsequently, we envision various scaffold remodeling tactics feasible via the proposed strategy. In addition, a reaction design to transpose the acyl group in a 1,2-fashion has also been proposed, enabled through a tethering plan. Specifically, the latter half of the proposal will detail the subsequent advancements possible with the proposed concept. A thorough investigation in this direction and development of the proposed transformations is believed to significantly streamline the late-stage diversification of bioactive molecules, thereby contributing to the discovery of therapeutic drugs.