Research Projects

Chemical synthesis plays a key role in advancing various scientific disciplines, ranging from materials science to drug discovery. Among the most powerful tools in modern synthetic chemistry are transition-metal-catalyzed functionalization, which provide versatile strategies for creating a wide array of structurally diverse and functionally important molecules. Despite their utility, these methods often depend on the use of pre-functionalized substrates to achieve both chemoselectivity and regio-selectivity in reactions. This reliance poses a limitation, as the availability of such pre-functionalized compounds is much narrower compared to the vast reservoir of unmodified feedstock chemicals. Moreover, the need for pre-functionalization restricts the adaptability of these catalytic methods when applied to structurally complex molecules such as natural products or pharmaceutical agents, which already contain multiple functional groups. As a result, there is growing interest in developing catalytic systems that enable the direct transformation of typically unreactive C–H bonds. The challenge lies in the intrinsic inertness of C–H bonds, which has led some to describe them as "unfunctional groups." This terminology underscores the difficulty in activating these bonds for direct transformations. Achieving selective transformation of unactivated C–H bonds, especially at remote positions within complex molecular frameworks, remains a significant challenge in contemporary organic synthesis. Such directing groups have been developed to achieve selective functionalization of arenes at the ortho, meta, and para positions, as well as to enable both nearby and remote functionalization of C(sp3)–H bonds. This research aims to develop transition metal-catalyzed methodologies using imidate and amidine directing groups for the precise, spatially controlled activation of remote C–H bonds. We will be investigating their influence on the selective functionalization of both distant C(sp2)–H and C(sp3)–H bonds within the same substrate. A key challenge lies in achieving high levels of chemo- and regio-selectivity. These directing groups will act as anchoring sites to guide transition metal catalysts such as Pd, Rh, Ir, Ru, Cu and Mn to otherwise inert positions in a molecule, enabling site-specific C–H activation. Through systematic studies of metal coordination and reactivity, this project will seek to establish versatile protocols for selective C–H bond functionalization. The approach will offer significant potential for synthesizing structurally complex molecules, including natural products and drug-like compounds. The spatial selectivity will be enabled by imidate and amidine groups that address challenges such as regio-isomeric mixtures and functional group compatibility. Overall, this work will advance C–H activation chemistry by introducing new strategies for remote functionalization and deepening our understanding of catalytic mechanisms and design.