Executive Summary : | The growing demand in the sustainable and selective production of pharmaceuticals and bulk/fine chemicals rejuvenated interest of organic chemists to develop new strategies. Fluorine and fluorine containing groups were found in modern pharmaceuticals and agrochemicals, but their abundance in nature is scare. Particularly, trifluoromethylthio (-SCF3) group containing metabolites are not found in nature, but it has attracted increasing interest in pharmaceutical and agrochemical designs due to its high lipophilicity property (Hansch constant, π = 1.44), which can greatly increase the transmembrane permeability and strong electron withdrawing nature that make the drug resistant to oxidation by oxidases through decreasing the electron density of the drugs. Due to the high importance of trifluoromethylthio group and lack of natural source, numerous methodologies were documented in the literature either through indirect or direct methods. In the last decade, number of nucleophilic and electrophilic trifluoromethylthiolating reagents were introduced, consequently, direct introduction of trifluoromethylthio group via generation of C-SCF3 bond in enantioselective manner have received special attention. However, enantioselective trifluoromethylthiolation are in its infancy and most of them are limited to enantiolselective trifluoromethylthiolation of enolate. Hence, the present proposal aims to achieve new enantioselective trifluoromethylthiolative functionalization of alkenes/polyenes employing suitable chiral catalyst with electrophilic trifluoromethylthiolating reagent, through the selective functionalization of enantioenriched thiiranium ion. Successful study of both intra and intermolecular trapping of thiiranium ion with nucleophiles would afford; 1) new, rapid and clean synthesis of various trifluoromethylthiolated building blocks, heterocyclic and polycyclic scaffold, and 2) will deliver a new class of enantioselective trifluoromethylthiolative functionalizations. Instead of simple trapping of formed thiiranium ion, terminating the trifluoromethylthiolative functionalization by rearrangement will be examined for the synthesis of chiral complex structural frameworks. In addition, trifluoromethylthiolation through dearomatization and desymmetrization would allow the synthesis of diverse functionalized heterocyclces such as indolizidines and quinolizidines and fused heterocycles and polycycles. Furthermore, utility of the developed methodologies will be demonstrated through the synthesis of trifluoromethylthiolated analog of biologically important molecules. |