Executive Summary : | The field of pharmaceutical chemistry is increasingly focusing on developing novel strategies for the construction of organic molecules, with fluorinated molecules being more successful motifs. Fluorinated molecules have exceptional biological properties, such as low size and high electronegativity, which encourage rapid synthesis of new drug candidates. However, the methods available for synthesizing novel and diversified fluoro or fluoroalkyl group (CF3) containing architectures are limited. This proposal aims to explore the efficient synthesis of novel organofluorine moieties through trifluoromethylated metal-allyl complexes. The regioselectivity of CF3-Pd-π-allyl complexes is different from simple allyl substrates due to the high steric hindrance and polar effect of the CF3 group. The versatile reactivity of these complexes as vinylating agents and the synthesis of trifluoromethyl substituted heterocycles with quaternary stereocenter are also reported. The proposal proposes axially chiral styrenes to form CF3-Pd-π-allyl complexes, an unexplored reactivity of CF3-Pd-π-allyl complexes to access versatile fluorinated architectures via [3+3] annulations, and the development of trifluoromethylated polycycles with quaternary stereocenters via cascade cross-coupling and intramolecular decarboxylative cycloaddition reactions. Additionally, a novel 5-(2,2,2-trifluoro-1-phenylethylidene)-1,3-dioxan-2-one is designed for the generation of CF3-Pd-zwitterionic intermediates. The results of these investigations will be presented at national and international conferences and published in leading journals. |