Transition metal-catalysis: Applications of dynamic kinetic resolution in total synthesis and developments of novel methodologies using heterogeneous Pd catalysts

Abstract: The first part of the thesis describes a general and efficient route for the enantioselective synthesis of various α-substituted ketones and their corresponding lactones. The two key steps in this synthesis are the ruthenium and CALB-catalyzed dynamic kinetic resolution (DKR) which provided the exocyclic acetates in high yields and excellent enantioselectivity and the subsequent Cu-catalyzed α-allylic substitution giving the corresponding α-substituted products with inversed stereochemistry in high yields. This synthetic route was applied to the synthesis of the naturally occurring (R)-10-methyl-6-undecanolide, via subsequent oxidative cleavage and Baeyer-Villiger oxidation.In the second part, a new microwave-assisted methodology using a heterogeneous Pd nanocatalyst for Suzuki cross-couplings and hydrogenation of alkenes is presented. The catalytic system proved to be compatible with a wide range of functional groups and heteroatoms. In general, excellent yields were obtained within 45 min for the Suzuki cross-couplings and within 30 min for the hydrogenation reactions. The catalyst exhibited high recyclability with a low leaching in both cases.A novel method to prepare γ-alkylidene lactones from alkynoic acids mediated by a heterogeneous Pd(II) catalyst is described in the last part of the thesis. The protocol proved to be highly stereo- and regioselective, affording the 5-exo-dig lactone as the single product in all cases. In general, internal alkynes were cyclized in high to excellent yields within 3 hours using 0.3 mol% of catalyst loading. For internal alkynes, the catalyst loading had to be increased to 0.5 mol% along with prolonged reaction times and elevated temperatures in order to obtained high yields. The catalyst showed some recyclability with low leaching.