Date of Award

Fall 2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Dockendorff, Chris

Second Advisor

Yi, Chae

Third Advisor

Clark, Joseph

Abstract

Reactions for the alpha functionalization of carbonyl compounds are important for the synthesis of complex organic materials such as pharmaceuticals, agrochemicals, and natural products. Current methodology used to perform these reactions is inefficient in that pre-activated coupling partners or sensitive catalysts are usually required. Described herein is the study and development of bifunctional and dual catalytic systems for carbon-carbon bond formation via the direct addition of unactivated carbonyl compounds to unactivated alkenes/alkynes. A dual catalyst system is one which utilizes two distinct catalysts to simultaneously activate separate reactants, and in a bifunctional catalyst the two catalytic components are present separately in a single molecule. Preliminary work involved the identification of novel bifunctional catalysts with heterocyclic scaffolds to promote asymmetric aldol reactions. The hybrid Lewis acid/Lewis base moieties incorporated into these catalysts acted to simultaneously activate "donor" aldehydes/ketones (via intermediate enamines) and "acceptor" aldehydes (via coordination to Lewis acids). These bifunctional scaffolds were subsequently modified to chelate copper(I) to promote the direct addition of aldehydes/ketones to alkynes. Density functional theory (DFT) calculations were used to optimize the design of precatalysts before synthesis and testing. Screening of numerous reaction conditions did not lead to the desired reactions, however, an X-ray crystal structure of precatalyst molecules bridging silver(I) metals was obtained. This suggested that the precatalyst was not binding to the Lewis acid in a productive fashion. Dual catalyst systems for the addition of aldehydes/ketones to alkenes/alkynes were also studied. DFT calculations led to the prediction that a bulky imidazolidinone as an organocatalyst and a bulky Pt-t-Bu-PyBOX-platinum(II) complex could facilitate the desired additions and preclude catalyst poisoning. Using this dual catalytic system, the intermolecular direct addition of an unactivated aldehyde to an unactivated terminal alkyne was discovered Lastly, a novel bifunctional catalyst was synthesized based on the PyBOX ligand previously mentioned. An X-ray crystal structure of this precatalyst bound to a palladium(II) salt showed the expected tridentate coordination of the metal, with a tethered amine available to act as an organocatalyst. Preliminary studies of this catalyst showed that it is also able to facilitate the intermolecular addition of aldehydes to terminal alkynes.

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