Method Development Towards Catalytic Transformations of Reactive Intermediates
AuthorDuncan, Julia Martha
AdvisorGeary, Laina M
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This program focused largely on accessing highly reactive intermediates, including ortho-quinone methides (o-QMs) and benzylic carbocations, from simple and easily accessed starting materials. The primary goals of each project were to access bioactive material or value added chemicals via the simplest and shortest route possible, limit the toxicity of each component of the reaction, and develop methods that were chemo- and regioselective with limited side reactions to provide a platform for further diastero- and enantioselective processes. We were able to accomplish such under broad Lewis acid catalyzed methods. Secondary goals, once a method was established, were to understand the mechanistic and physical parameters of the reaction process such that the limitations and scope could be detailed for future development and applications.Chapter two details explorative chemistry towards heterocannabinoid species. Oxidative palladium (II) catalysis was employed to generate o-QM in situ via intermolecular activation of a styrene olefin. Though limited success was realized for the target compound, proof of mechanistic concept was accomplished when synthesis of chromans and benzopyran derivatives were found. Later efforts focused on an aldol approach towards o-QMs, which are rarely employed.Chapter three examined a Lewis acid catalyzed synthesis of unsymmetrical ethers from direct functionalization of benzyl alcohols. This project demonstrated the powerful utility of Lewis base tuning of Lewis acids, while concurrently providing a simple method for chemoselective carbocation control. Though we did not employ any complex methods, the mechanistic investigations revealed some unusual kinetic behavior that suggest convergent competing pathways towards the ether products.To extend our interest towards carbocation chemistry, a unique palladium-silver catalyzed aza-Piancatelli rearrangement of furcarbinol acetates was explored in chapter four. An in situ IR monitoring technique was used to extrapolate mechanistic insight from preliminary kinetic data. A cationic palladium species was proposed to act as the active catalyst, while the silver salt had dual functionality in both activation of the palladium catalyst and stabilization of an off-cycle carbocation via pseudo-halogen scavenging.