Publication Date

2014-07-29

Availability

Embargoed

Embargo Period

2016-07-28

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Chemistry (Arts and Sciences)

Date of Defense

2014-06-25

First Committee Member

Norito Takenaka

Second Committee Member

Angel Kaifer

Third Committee Member

James N. Wilson

Fourth Committee Member

Konstantinos Kavallieratos

Abstract

The Diels – Alder reaction and the Claisen rearrangement are pericyclic reactions involving a cyclic transition state. In the nitroalkene Diels – Alder reaction, efforts of LUMO-lowering catalysis through activation of nitroalkenes by metal-based Lewis acids have proven unsuccessful. Conversely, studies have shown that double hydrogen bond donors possess symmetrical coordination sufficient for activation of nitroalkenes. In the Claisen rearrangement, while there have been rare reports of enantioselective catalysis via Lewis acids, studies have shown that in rearrangement of chorismate, the enzyme chorismate mutase stabilizes the chair-like transition state through hydrogen-bonding interactions. In light of this, highly enantioselective Claisen rearrangements through the use of guanidinium ions have been achieved. This highlights the potential for hydrogen bond donors as potential catalysts for these pericyclic reactions. The development of helical chiral double hydrogen bond donor catalysts for the enantioselective nitroalkene Diels – Alder reaction of 5-substituted pentamethylcyclopentadiene substrates and nitroethylene is described in chapter two. The use of 11,12-benzo-1-aza[6]helicene based hydrogen-bond donor catalysts effectively activates nitroalkenes through LUMO-lowering catalysis to provide desired Diels – Alder products in up to 40% ee. Catalyst evaluation and expansion of the substrate scope are discussed. A synthetic route was designed and performed to access 1,4,5,5-tetrasubstituted cyclopentadienes and the evaluation of these new diene substrates are discussed. The catalysis of an O-allylated β-ketoester model substrate by helical chiral hydrogen bond donor catalysts is described in the third chapter. Initial evaluations of existing helical hydrogen bond donor catalysts and the development of new helical chiral dimers are discussed. These helical dimers are then synthesized and are observed to provide yields of up to 96% in the Claisen rearrangement of the model substrate. The final chapter describes the efforts to develop a third generation synthesis of 1-azahelicenes to provide them in an enantiopure form. Studies of the initial step, asymmetric formation of a biaryl intermediate utilizing existing coupling methods are discussed and a highly aymmetric intramolecular coupling of an intermediate providing enantioenriched 1-aza[6]helicene are discussed.

Keywords

Asymmetric catalysis; Hydrogen-Bond; Helicenes; Nitroalkene Diels-Alder; Pericyclic; Enantioselectivity

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