Convergent and Tandem Strategies in Iridium-Catalyzed Asymmetric Hydrogenation of Olefins

Sammanfattning: The work presented in this thesis describes the development of enantioselective methods and their corresponding mechanistic studies to expand the field of catalytic asymmetric hydrogenation. Efficient catalytic systems based on iridium complexes were designed and employed in convergent and tandem strategies to prepare important optically enriched organic compounds. In Chapter 2, a novel and straightforward method for the diastereoselective synthesis of isomerically pure enamides is presented. These enamides were employed as substrates to explore the process of convergent asymmetric hydrogenation. Both E- and Z- isomers were reduced with high enantioselectivity to the same enantiomeric product, thus allowing the use of E- and Z-mixtures as substrates. Mechanistic studies were carried out and revealed that the hydrogenation may occur via different pathways.In Chapter 3, the enantioconvergent hydrogenation strategy is expanded to fluoromethylated substrates. Challenging olefins bearing the CFx group as the only functionality were successfully reduced and employed as E/Z-mixtures. The synthesis of precious enantioenriched fluorinated molecules was achieved and mechanistic studies were carried out to understand this convergent hydrogenation.In Chapter 4, a cascade condensation-hydrogenation for the formation of chiral lactams is presented. Using fine-tuned reaction conditions, unsaturated lactams were formed and then stereoselectively reduced in situ. This strategy offers several advantages when compared to stepwise procedures.In Chapter 5, a double convergent isomerization-hydrogenation of allylic alcohols is reported. Several substrates, each consisting of a mixture of up to four isomers, were converted to single isomer of a tertiary alcohol with high diastereo- and enantioselectivity. Mechanistic studies were performed suggesting that the E/Z-isomerism of the substrate is resolved in the 1,3-rearrangement, meanwhile the stereocenter bearing the hydroxyl group is enantioenriched via dynamic kinetic resolution.