Development of Catalyst Systems for Regio- and Enantioselective Transformations of Amine and Ether C-H Bonds

Abstract

This dissertation describes the development of novel catalyst systems that could promote the regio- and enantioselective transformations of C-H bonds contained in N-alkylamines and ethers through Lewis acid-mediated hydride abstraction processes. The progress made in C-H functionalization of N-alkylamines and ethers that served as the intellectual foundation of this dissertation research are summarized in Chapter 1. Despite notable advances, the development of broadly applicable, enantioselective, and catalytic protocols to functionalize C-H bonds in N-alkylamines and ethers with high regio- and stereo-selectivity was regarded as an unsolved problem when we started this dissertation research. In an effort to overcome these fundamental limitations, we first identified a B(C6F5)3/Cu-PyBOX cooperative catalyst system for the enantioselective conversion of a-amino C-H bonds through the generation of an iminium by (F5C6)3B-catalyzed hydride abstraction process (Chapter 2). We then envisioned that in situ generated iminium ions could be further deprotonated to furnish an enamine intermediate, which may react with electrophilic species for a-amino C-H functionalization. The design and development of such a catalyst system were discussed in Chapter 3. Finally, we disclose enantioselective Cu–BOX-catalyzed hetero Diels-Alder reactions of enol ethers generated through Ph3C+-mediated oxidation of alkyl ethers. (Chapter 4).