Research Projects

Transition metal-catalyzed C–H bond functionalization has emerged as a powerful strategy for constructing complex molecules in a step- and atom-economical fashion. Cobalt, as an earth-abundant and cost-effective first-row transition metal, offers unique opportunities in this area due to its redox versatility and capacity to form high-valent intermediates. However, the field of asymmetric C–H bond functionalization under cobalt catalysis remains underdeveloped, primarily because of challenges in inducing and controlling chirality during catalysis. Most reported systems rely on substrate-derived chiral elements or bidentate directing groups (DGs) (due to chiral bidentate ligands can take care of two coordination site out of six, eg. salox type), which limit scope, modularity, and practical application. This project aims to address these limitations by engineering new classes of air- and moisture-stable chiral cobalt(III) complexes capable of mediating enantioselective C–H bond functionalization. The central hypothesis is that well-defined chiral environments—achieved either through planar chiral ligands, stereogenic cobalt centers, or external chiral tridentate ligands (instead of laborious chiral Cp-ligands (cramer’s approach) or chiral acid (Matsunaga’s approach)—can significantly enhance the enantioselectivity and applicability of cobalt catalysis. We propose a three-pronged approach: 1. Design and resolution of planar chiral Cp#Co(III) complexes featuring sterically demanding Cp# ligands. 2. Access to enantiopure [CpCo(allyl)(L)]⁺ complexes with stereogenic metal centers via stoichiometric and catalytic resolution strategies. 3. Development of chiral tridentate ligands that eliminate the need for covalently attached DGs, enabling more general and modular enantioselective C–H functionalization. The rationality behind the Scientific Hypotheses and Model is as follows: • Planar chirality embedded in Cp# ligands can serve as a persistent chiral environment that imparts high enantioselectivity across diverse transformations. • Stereogenic-at-cobalt centers in allyl-Co complexes can be reliably generated and harnessed as new chiral catalysts. • Tridentate ligand frameworks mimicking substrate-bound cobaltacycles can transfer stereochemical information to the substrate without requiring DG installation, enabling direct C–H activation in complex molecules. The identified defined target planned to achieve through this proposal: • Target I: Synthesize a series of Cp# ligands (# defines bulkier ligands) and prepare Cp#Co(III) complexes. Chiral resolution will be achieved via auxiliary-based diastereomeric separation (e.g., with (S)-proline), followed by auxiliary removal to yield planar chiral Cp#CoX₂ dimer. Catalytic testing in asymmetric C–H functionalization will evaluate reactivity and selectivity. • Target II: Generate racemic [Cp*Co(allyl)(CO)]⁺ complexes, then use chiral amine auxiliaries or catalytic resolution via Co(II)/Salox systems to access enantiopure Co(III) species. Structural and kinetic data will guide mechanistic understanding. • Target III: Design modular L–L–X or L–X–L chiral ligands to create octahedral cobalt complexes mimicking the DG-bound intermediates. These ligands will be evaluated in model asymmetric C–H functionalization reactions using substrates with native functional groups (e.g., alcohols, amides). If successful, this project will establish novel design principles for asymmetric catalysis using cobalt—introducing durable chiral platforms, uncovering stereochemical models for chirality transfer, and removing the dependence on substrate-installed DGs. This will significantly expand the synthetic utility of cobalt catalysis, offering new tools for enantioselective transformations of relevance to pharmaceuticals, natural products, and materials science. From a fundamental standpoint, the project will contribute to new reactivity paradigms involving first-row transition metals.