Publication Date

2014-07-15

Availability

Embargoed

Embargo Period

2016-07-14

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Chemistry (Arts and Sciences)

Date of Defense

2014-06-27

First Committee Member

Norito Takenaka

Second Committee Member

Angel Kaifer

Third Committee Member

James N. Wilson

Fourth Committee Member

Kathleen Rein

Abstract

The design and development of novel chiral catalysts for efficient construction of carbon-carbon bonds, especially in an enantioselective manner, stays as a major goal for organic chemists. In the last two decades, various organocatalysts have been developed to solve important problems in asymmetric organic synthesis. Novel chiral catalysts based on previously unexplored 1-azahelicenes have been developed by our group and found great applications in mechanistically unrelated reactions. As part of Ph.D. research projects, the design and development of new helical chiral catalysts based on 11, 12-benzo-1-aza[6]helicene N-oxide and their applications in asymmetric synthesis are presented in this thesis. First, the development of a diastereomeric salt-mediated optical resolution of 11,12-benzo-1-aza[6]helicene will be discussed. This process performed best when (-)-dibenzoyl-L-tartaric acid monohydrate was used as resolving agent and acetonitrile was used as solvent. Second, substrate scope of the helical chiral hydrogen-bond donor catalyzed nitroalkene Diels-Alder reaction has been extensively studied. An efficient, synthetically versatile synthesis to access a new class of dienes has been designed and developed. The activity profiles of these new dienes have also been tested in the context of nitroalkene Diels-Alder reactions. Third, a series of novel helical chiral catalysts has been designed and synthesized via simple reactions. These catalysts include both Lewis base catalysts and Brønsted acid catalysts. Structures of some of the catalysts have been elucidated unambiguously by X-ray crystallography. Last, the asymmetric allylation of ketoimines by helical chiral pyridine N-oxides have been developed to access enantiomerically pure α-trisubstituted homoallylic amines. Study revealed that a product inhibition probably occurred in this reaction, and extensive efforts have been devoted to solve this problem. Good yield and high level of selectivity has been realized with this allyltrichlorosilane-mediated reaction by utilizing a Lewis basic solvent.

Keywords

organocatalysis; asymmetric synthesis; chirality; helicenes; nitroalkene Diels-Alder reaction; ketoimine allylation

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