| Description |
Design of synthetic strategies that allow facile access to a stereocenter in a catalytic fashion is highly desirable. This dissertation details the development of a palladium-catalyzed process that enables strategic coupling of alkenyl groups with multisubstituted alkenes in a highly enantioselective fashion to generate tertiary or quaternary allylic stereocenters. Chapter 1 focuses on the existing modern methods that allow incorporation of an alkenyl moiety in a catalytic and enantioselective manner. In Chapter 2, a palladium-catalyzed intermolecular enantioselective coupling of alkenyl triflates with acyclic primary or racemic secondary alkenols is described. Applying this strategy, a wide array of functionalized alkenyl groups can be installed at positions β, γ, or δ to a carbonyl group in high enantioselectivity. It is necessary to use electron deficient alkenyl triflates to direct selective β-hydride elimination and prevent catalyst arrest. To demonstrate the synthetic potential of this process, a two-step derivatization of the resulting Heck product led to the formation of a tricyclic core structure, present in various natural products. The application of the redox-relay Heck strategy to trisubstituted alkenes afforded the construction of quaternary stereocenters and is described in Chapter 3. Specifically, the reaction of terminal (E)-alkenyl triflates, in the presence of a Pd(0) catalyst and a chiral ligand leads to the formation of allylic quaternary stereocenters in high enantioselectivity. iv To further illustrate the synthetic applicability of this transformation, the alkene introduced in a chiral Heck product was readily processed via simple organic transformations to access remotely functionalized chiral tertiary alcohol, acid, and amine products. Finally, Chapter 4 explores the applicability of highly polarized alkenes as potential substrates in the redox-relay Heck reaction. A number of electron-deficient alkenyl triflates underwent selective coupling with acyclic aryl enol ethers in the presence of a chiral palladium catalyst to provide chiral allylic ether products in high yields and excellent enantiomeric ratio. Furthermore, the significance of this process was demonstrated through the formation of chiral allylic alcohol achieved via a simple cleavage of the p-methoxyphenyl moiety. |
