Research Projects

Fluorinated organic molecules have superior physical, chemical, and biological properties compared to non-fluorinated ones. They also exhibit better lipophilicity towards proteins and enhanced metabolic stability. This makes molecular scaffolds with fluorine atoms advantageous in agrochemical and pharmaceutical applications. The proposal aims to discover new synthetic regimes for stereoselective fluorination of inert C-H bonds, non-directed fluorination of biologically relevant molecules, and 1,2-fluorodifunctionalization of ynamide scaffolds. The synthetic work plan includes asymmetric fluorination of inert C-H bonds using a chiral directing group and chiral ligand coordination with a transition metal catalyst. This leads to asymmetric C-H activation followed by oxidative addition of electrophilic fluorinated species to the Mn complex, generating Mn+2 intermediate and reductive elimination of Mn+2 intermediate. Non-directed C-H fluorination involves a combination of bidentate pyridyl sulfoximine DG, monodentate N-acetyl ligand, and electrophilic fluorinating agents for site selective functionalization of inert C(sp2)-H bonds. These strategies can be successfully implemented for late-stage fluorination of biologically relevant molecules (BRMs). Ynamide 1,2-fluorodifunctionalization involves a transition metal-mediated addition of organo-TM-complex across the ynamide C-C triple bond and quench of vinyl-organometallic intermediate with a nucleophilic fluoride (F-) species. This method can be used for the efficient synthesis of CL3pro SARs-2 inhibitors.