Faculty Advisor or Committee Member

Marion H. Emmert, Advisor

Faculty Advisor or Committee Member

Arne Gericke, Committee Member

Faculty Advisor or Committee Member

Shawn C. Burdette, Committee Member

Faculty Advisor or Committee Member

N Aaron Deskins, Committee Member

Identifier

etd-041619-062319

Abstract

Presented herein is the development, optimization and mechanistic investigation of an Cu catalytic system for the oxidation of sp 3 C-H bond of simple arenes to form C-N bond in a direct manner. Due to the prevalence of nitrogen containing molecules among biologically active synthetic and natural compounds, synthetic chemists have always been motivated to develop new efficient ways to directly transform ubiquitous carbonhydrogen (C-H) bonds into carbon- nitrogen (C-N) bonds. Recent advances in transition metal catalyzed C-H amination has demonstrated that it is not only possible but also practical to functionalize C-H bonds that are often considered inert in one step, circumventing more classical, sequential functional group interconversion approaches. Existing catalytic systems that promote the transition metal-catalyzed, amination of sp 3 C-H bonds displayed certain limitations, especially the lack of built-in versatility and stability in their amination reagents. To overcome these drawbacks of these existing catalytic system, our group developed a new Cu amination protocol that deployed versatile hydroxylamine-based with general structure RSO 2 NH-OAc as amination reagents. Although the reactivity of the catalytic system ranges from moderate to good, the catalytic system provided promising results using simple arene substrates. Further detailed mechanistic studies revealed that the reaction undergoes an unprecedented two subsequent cycles divided by a major intermediate PhCH 2 (NTsOAc). The proposed mechanism is consistent with radical clock experiments, observed reaction profiles, the need for excess of substrate, and the documented role of the ligand in the catalytic system. The exciting proposed mechanism led to a new type of copper catalyzed amination reaction using N- fluorobenzenesulfonimide (NFSI) as oxidant, which overcomes the need to use an excess of substrate. A wide range of unactivated amines HNR 1 R 2 , including sulfonamide and benzamide, can be used as amine sources, which enables the installation of different nitrogen groups on benzylic sp 3 C-H bond of a variety of substrates in moderate to excellent yield. Moreover, mechanistic experiments and critical analysis of related reactivity in the literature provide insight into the catalytic cycle, resulting in a proposal that details the role of both oxidant and amine source in the new system.

Publisher

Worcester Polytechnic Institute

Degree Name

PhD

Department

Chemistry & Biochemistry

Project Type

Dissertation

Date Accepted

2018-12-14

Accessibility

Restricted-WPI community only

Subjects

Amination, C-H functionalization, Transition Metal Catalysis

Available for download on Saturday, April 16, 2022

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