Research Projects

Organoboronate esters are widely used as synthetic building blocks in diverse chemical transformations relevant to pharmaceuticals and materials. Additionally, organoboronates are broadly featured in diverse potent drug candidates. Notably, the organoboronates available today are solely derived from organic halides or organo magnesium/organo lithium compounds, which produce substantial wastes, involve multiple synthetic steps, and rely on the availability of suitably substituted organic halides. Direct C-H bond borylation of arenes and heteroarenes provides an alternative and sustainable approach addressing the noted drawbacks. Unfortunately, most of the direct borylation processes use the expensive and environmentally deleterious noble Pd, Rh, and Ir-based metal catalysts, with iridium being the dominant. The high-cost, low availability, and less environmentally friendliness of these catalysts deter them from broader and large-scale industrial exploration. Therefore, a cautious and strategic design of cost-effective and sustainable catalyst systems derived from environmentally benign and Earth-abundant metals, like iron, is crucial for the sustainable C-H borylation of synthetically and pharmaceutically relevant arenes and heteroarenes. Iron is the most Earth-abundant transition metal and is non-toxic. The iron-based catalysts generally show unique catalytic activities compared to the expensive 4d and 5d transition metals. The iron(II) and iron(0) species exhibit d⁶ and d⁸ configurations, respectively, and can be stabilized by the strong field phosphine and carbene ligands in low-spin states. The accessible low-spin state is essential for activating C-H (substrate) and B-H (or B-B; borylating agent) bonds and their binding to the iron. Therefore, in this project, we are targeting to establish rationally designed hybrid PN³N and CNN-ligated low-valent Fe(0)/Fe(I) catalyst systems (I & II) for the direct and sustainable borylation of arenes and heteroarenes. The strong sigma-donation from alkyl-substituted P-center/carbene-center and hybrid redox-active ligand would stabilize d⁸/d⁶ low-spin states of iron and facilitate the arene’s C-H activation. A redox-active backbone would assist in the reactivity of B-H/B-B bonds by electron shuffling between iron and ligand. Moreover, altering the steric on P- and carbene-arms would provide the selectivity in C-H borylation. We also propose developing a (PN³N)Fe system III containing urea functionality, which will be ideal for carbonyl-moiety-containing arenes, wherein the selectivity would be controlled by a hydrogen-bonding secondary interaction between the catalyst backbone and substrate. All the developed iron complexes will be thoroughly characterized and optimized for the selective borylation of arenes and heteroarenes. The protocol’s scope will be demonstrated for the synthesis of diverse borylated compounds that are relevant to industrial or biological applications. With the optimized conditions and efficient catalyst system, we will move towards the synthesis of advanced precursors of pharmaceutically relevant ingredients, such as borylation of fluoro-arenes, trifluoromethyl-arenes, fluoroalkyl-arenes that are crucial precursors for the novel drug candidates. We want to scale up (5-10 g scale) a few borylated products commonly used in industries. Moreover, we will attempt the synthesis of bio-relevant organoboronates employing our developed strategy. We strongly believe that our approach to develop robust catalyst systems and novel methodology for the borylation of diverse arenes and heteroarenes will be highly selective and environmentally friendly. The developed catalyst and process would generate significant interest in chemical industries.