Bio and Transition Metal Catalysis with Directing Group-Enabled Green Chemistry

Abstract

Developing synthetic strategies and protocols that enable functionalization of C-H bonds is of great interest to the organic chemists. The high stability and inert nature of these bonds makes them challenging to break. Despite the progress made in this area, low atom economy, high E-factor and variable selectivity are still major challenges. Our research addresses some of these challenges through enzymatic catalysis. The first part of this thesis focuses on directed palladium-catalysed vicinal carbofunctionalization using glycine-extended tridentate ligands. A tridentate ligand bearing a quinoline, aryl amide and alkyl amine moieties proved highly reactive for the anti-Markovnikov hydrofunctionalization of tethered unactivated olefins, allowing reactions at temperatures as low as 25 °C, while its regioisomer with the amide carbonyl transposed only one position away shows limited reactivity. Experimental and computational study explores the scope of this reaction and demonstrates how the Pd-substrate complexes employ various favorable or unfavorable protonation states during the mechanism. The second part of the thesis employed a lipase (Thermomyces languinosa) immobilised on a solid support to mediate a one-pot, multistep chemoenzymatic catalysis. We developed as a proof-of-concept a metal directed C-H functionalization that occurred under similar reaction condition as biocatalyzed counterpart. A metal catalyzed trifluoromethylation being flanked by biocatalytic amidation to install, and transamidation to remove the directing group. We optimized the reactions and made an entry towards the integration into a one-pot combined chemo-enzymatic reaction cascade.