Transition Metal-Catalyzed Enantioselective Alpha Functionalization of Nitrogen and Oxygen-Containing Heterocycles

Citation

Jette, Carina Ivonne (2021) Transition Metal-Catalyzed Enantioselective Alpha Functionalization of Nitrogen and Oxygen-Containing Heterocycles. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/qs4z-3803. https://resolver.caltech.edu/CaltechTHESIS:11192020-190811434

Abstract

Research in the Stoltz group is focused on the development of synthetic methods for the preparation of stereochemically rich molecules and the total synthesis of complex natural products. One major theme of our group’s methods development is transition-metal catalyzed α-functionalization of carbonyl derivatives, with a particular focus on the development of allylic alkylation protocols. Although the α-functionalization of carbonyl derivatives such as enolates, has been extensively studied, the use of nitrogen and oxygen- containing heterocycles, such as lactams and lactones, remains under- developed. These types of nucleophiles are significantly more reactive, and in the case of the γ-butyrolactones and γ-lactams, may be smaller in size. Because of these differences, the conditions that have been developed for the functionalization of carbonyl derivatives such as ketones does not translate well to these nucleophiles. Furthermore, within the context of enantioselective functionalization, the unique characteristics of these nucleophiles necessitates the development of large, bulky ligands that enable the formation of a very well-defined chiral environment around the transition metal catalyst. This thesis mainly describes strategies that have been developed for the enantioselective α-functionalization of nitrogen and oxygen-containing heterocycles, with a particular focus on the γ-lactams and γ-butyrolactones.

Thesis Files