The Modular Synthesis and Functionalization of Cyclic Compounds Using Modern Methods

Author: Lacker, Caitlin Rebecca

Year: 2022

Degree: Dissertation (Ph.D.)

Advisor: Reisman, Sarah E.

Committee Members: Fu, Gregory C.; Reisman, Sarah E.; Hsieh-Wilson, Linda C.; Stoltz, Brian M.

Option: Chemistry

DOI: 10.7907/61ky-5w83

Abstract

Accessing libraries of similar compounds quickly is important in the pharmaceutical industry, as it allows for the expedient investigation of a wide variety of parameters. An efficient strategy to access compounds of interest is to start from a single intermediate containing an interesting or pharmaceutically active structure and decorating it with varying functionality to generate a library of related compounds. Cross-coupling is a powerful tool for this type of divergent, modular approach.

Herein, we discuss several strategies geared towards the synthesis of small libraries of compounds of interest. First, a modular approach towards a library of enantioenriched trans cyclobutanes is discussed. This strategy allows for the synthesis of diverse substrates from a single enantioenriched intermediate, and this approach was applied to the synthesis of the small molecule (+)-rumphellaone A. Finally, the development of an enantioselective nickel-catalyzed photoredox cross-coupling to form N-(hetero)benzylic azoles in collaboration with researchers at Merck is discussed.

Files