Date of Graduation

8-2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Degree Level

Graduate

Department

Chemistry & Biochemistry

Advisor/Mentor

Zheng, Nan

Committee Member

Chen, Jingyi

Second Committee Member

Durham, Bill

Third Committee Member

Allison, Neil T.

Fourth Committee Member

McIntosh, Matthias C.

Keywords

Pure sciences; Alkynes; Cycloaddition; Cyclopropylanilines; Visible light photocatalysis

Abstract

Over the past decade, pharmaceutical industries have prioritized their focus on discovering new innovative drugs, yet the syntheses are often either inefficient or the approach of environmental sustainability presents a great deal of concern. Moreover, the methodology developments for amine syntheses have continued to flourish due to their important role and wide use in pharmaceutics. Yet their syntheses often lack sustainability and efficiency. Synthetic chemists have continued to explore potential innovative avenues for conducting chemical reactions more effectively and efficiently. One of the most abundant, renewable natural resources is solar energy and to harvest, use, and store it directly is an ongoing development. To reduce our dependency on fossil energy sources, methods of direct and proficient conversion of solar energy to chemical energy become critically important. Recently, visible light photoredox catalysis has become a highly prominent tool in the development of many successful organic transformations. This work describes an innovative approach of using visible light photocatalysis to develop efficient one-step syntheses for the construction of structurally diverse carbocycles substituted with amines from simple starting materials under mild conditions.

Under photocatalysis, amines can function as both the sacrificial electron donor and substrate. Incorporating the oxidation of the amine and a subsequent irreversible reaction will allow the amine to posses its dual roles. To accomplish this, cyclopropylanilines were used and subjected to ring opening to form reactive β-carbon radical iminium ions via nitrogen radical cations upon oxidation of the cyclopropylanilines. As a result, an intermolecular [3+2] annulation of cyclopropylanilines with alkynes was developed to afford highly useful synthetic intermediates and motifs such as fused indolines, which are found in various bio-active alkaloids and pharmaceuticals. This method exhibited significant group tolerance particularly with heterocycles. Moreover, the [3+2] annulation enabled rapid assembly of diverse cyclic allylic amine derivatives. Expansion of the [3+2] annulation to include substituted cyclopropylanilines and other types of π-bonds, such as enynes and diynes to afford structurally diverse carbo- and heterocycles were studied. Lastly, a protocol for an oxidative cleavage of N-aryl group was successfully accomplished upon screening various oxidants and installing various removable aryl or heteroaryl group.

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