Date of Award

2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

Marisa C. Kozlowski

Abstract

The N-heterocyclic carbene catalyzed hetero-Diels-Alder cycloadditions of α,β-unsaturated enones with NHC-enolate adducts generate γ,δ-unsaturated δ-lactones in high yield and enantioselectivity. A quantitative structure-activity relationship analysis of experimental results using a series of NHC ligands reveals a strong correlation between selectivity and steric and electronic parameters. The stereoselectivity-determining step is determined to proceed through a concerted, asynchronous, zwitterionic hetero-Diels-Alder cycloaddition rather than a Michael addition or Claisen rearrangement. A transition state model is developed that accurately predicts the experimental results. A CH–π interaction acting in concert with an anion-π interaction is determined to be the cause of observed electronic effect. The steric contribution is derived from steric clashes between the catalyst and the approaching enone.

The N-heterocyclic carbene and hydroxamic acid co-catalyzed kinetic resolution of secondary cyclic amines developed by the Bode lab furnishes enantioenriched amides and amines with selectivity factors up to 74. A mechanism study revealed that the reaction proceeds through a novel hydroxamic acid proton transfer modification of the concerted aminolysis pathway. Systematic analysis of transition state conformations revealed the steric effects that lead to the observed selectivity. The transition state model developed predicted the observed selectivity factors for two hydroxamic acid esters.

Part II. The asymmetric oxidative coupling of phenols remains a significant challenge in organic chemistry. Binuclear oxovanadium amino acid Schiff base catalysts developed by Gong and Sasai for naphthol coupling were determined to be batch-dependent when applied to phenol coupling. Optimization of catalyst preparation diminished this problem.

Amino ester Schiff base catalysts allowed for in situ complex formation and improved selectivities at the expense of conversion. Novel BINOL-like scaffolds failed to improve the selectivity in the phenol coupling reaction. A series of tethered catalysts ultimately led to the identification of monomeric catalysts that can produce chiral bisphenols in high yield and moderate enantioselectivity.

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