Reductive C-C Bond Construction Strategies by Samarium and Nickel Catalysis

Author: Shin, Chungkeun

Year: 2026

Degree: Dissertation (Ph.D.)

Advisor: Reisman, Sarah E.

Committee Members: Stoltz, Brian M.; Hadt, Ryan G.; Manthiram, Karthish; Reisman, Sarah E.

Option: Chemistry

Abstract

Reductive carbon–carbon bond construction is a powerful strategy for rapidly assembling molecular complexity from structurally diverse precursors. Leveraging low-valent or open-shell metal intermediates, reductive catalysis enables efficient bond formation in complex systems. This thesis describes the development and study of reductive catalytic strategies for C–C bond formation using samarium and nickel catalysis.

Chapter 1 describes the development of a samarium-catalyzed intermolecular reductive cross-coupling of ketones and acrylates enabled by Sm(III)–alkoxide protonolysis. This strategy overcomes a key barrier to Sm(II) catalysis by converting redox-inactive Sm(III)–alkoxide intermediates to redox-active Sm(II) species under mild turnover conditions. Mechanistic insights are provided by electrochemical studies and examination of the solvent–acidity cross-relationship. The modularity of this approach lays the groundwork for more generalized strategies in the future development of reductive Sm catalysis.

Chapter 2 presents the development of a nickel-catalyzed asymmetric arylation of α-substituted imides. Two complementary approaches are described, wherein α-chloroimides are paired with aryl iodides and α-mesylates are paired with aryl bromides to match the relative rates of imide activation and aryl halides oxidative addition. This methodology provides rapid access to pharmaceutically relevant highly enantioenriched α-aryl imides.

Chapter 3 provides an overview of Ni-catalyzed asymmetric C(sp3)–C(sp3) cross-electrophile coupling. This chapter highlights two complementary stereochemical paradigms of stereoconvergent coupling and stereoretentive coupling, with an emphasis on their scope, mechanistic insights, and limitations.

Chapter 4 discusses efforts toward a Ni-catalyzed stereoretentive–stereoselective decarbonylative C(sp3)–C(sp3) cross-coupling method. This work establishes highly stereoretentive alkylation of enantioenriched pyridyl esters with primary alkyl iodides. Efforts to expand this reactivity to secondary alkyl iodides are then described, with the goal of forging products bearing vicinal stereogenic centers. These studies lay foundation for the future development of reductive asymmetric alkyl–alkyl cross-coupling reactions.