Research Projects

This research project aims to develop a novel class of bifunctional iridium catalysts capable of achieving remote enantioselective C(sp²)–H borylation through precisely engineered secondary coordination-sphere interactions. At its core, the study addresses one of the most fundamental challenges in synthetic chemistry - achieving precise stereochemical control at distant positions from the catalytic center, overcoming entropic penalties and competing diastereomeric pathways. Our innovative strategy involves engineering chiral bipyridine and phenanthroline ligands equipped with strategically positioned Lewis acid and non-covalently interacting sidearms, creating a sophisticated secondary coordination sphere that can simultaneously govern both regioselectivity and enantioselectivity in C–H activation reactions. The catalyst design draws inspiration from enzymatic systems, mimicking nature’s ability to use non-covalent interactions for precise molecular recognition and transition state stabilization, while maintaining the versatility and robustness of transition metal catalysis. The proposed catalyst architecture integrates three critical components: (1) a conserved bipyridine-iridium catalytic core for efficient C–H activation, (2) a strategically positioned chiral environment derived from rigid-chiral frameworks, and (3) tethered Lewis acid and non-covalently interacting sites for substrate alignment through secondary-sphere interactions. This modular C₁-symmetric design enables systematic optimization of steric, electronic, and coordinative parameters to achieve simultaneous control over both regioselectivity and enantioselectivity for diverse substrate classes. Key objectives include developing a comprehensive ligand library, establishing design principles for long-range chirality transfer through combined experimental and computational studies, and extending the methodology to construct challenging stereocenters at carbon and heteroatoms (S, P, Si) as well as axial, planar, and helical chirality. Key experiments will focus on desymmetrization reactions and kinetic resolutions. The project will also demonstrate practical applications through late-stage functionalization of bioactive molecules, offering transformative potential for pharmaceutical and agrochemical synthesis. Preliminary results with H8-BINOL-derived catalysts have already achieved remarkable stereocontrol (92-97% ee) in meta-C-H borylation and unprecedented kinetic resolution (s-factor up to 19.5), providing strong validation of our innovative approach and its potential to redefine the boundaries of C–H functionalization chemistry. Successful implementation of this research will have transformative implications across multiple scientific domains. In fundamental science, it will provide new insights into entropy compensation strategies for distal functionalization and establish quantitative structure-selectivity relationships in asymmetric catalysis. From a practical standpoint, the technology will enable more efficient synthesis of chiral pharmaceuticals, agrochemicals, and functional materials by allowing direct, late-stage modification of complex molecules. The project’s broader impact extends to advancing our understanding of biomimetic catalyst design principles and opening new avenues for controlling reactivity through secondary coordination-sphere engineering.