Research Projects

Ring fluorinated/carbofluorinated azoles embody a large number of drugs, drug discovery scaffolds and agrochemicals, especially for crop protection, that constitute a huge commercial market. Hence, synthesis of fluorinated/carbofluorinated azoles has curved out a niche area in methodological development and process R&D. While confined to industrial research only a few years back, the field has recently opened up for academic pursuits. While most of the research have focused on fluorinated/carbofluorinated 6-membered (hetero)arenes, synthesis of fluorinated/carbofluorinated azoles, while limited to few scattered reports, have received scant attention. In view of importance of fluorinated/carbofluorinated azoles in drugs and agrochemicals, together with recent emphasis on “fluorine-effect” for improving druggability profiles and use of [18]F for PET imaging, the proposed project aims to develop modular synthesis of fluorinated/carbofluorinated imidazole and pyrazoles. Harnessing our extensive experience in Cu-catalyzed Chan-Lam coupling reactions of various heterocycles, a novel modular two-step synthesis of fluorinated/carbofluorinated imidazoles and pyrazoles via regioselective Hartwig borylation of parent azoles followed by Cu-catalyzed fluoro/carbofluoro-deborylation reaction (“fluoro” variant of Chan-Lam coupling) is proposed. This scaffold based approach is attractive on several counts: modular strategy, step-economy, mild reaction conditions and high chemo- & regioselectivity, which are ideally suited for scale-up options and rapid analog synthesis for medicinal chemistry campaigns. The proposed two-step methodology, specifically, aims at synthesis of isomer-specific fluorinated/carbofluorinated imidazole and pyrazole building blocks and their applications to (a) novel synthesis of important agrochemicals and drug intermediates and (b) late-stage fluorination/carbofluorination of existing drugs for exploring new improved therapeutic agents exploiting the “fluorine effect”. The results would be of high interest in pharma and agro industry.