Novel platforms toward C–C bond formation, stereocontrol, and expedited reaction generality

Abstract

In the past decade and a half, photoredox catalysis has emerged as a powerful and widely adopted catalytic platform in the field of organic synthesis. In particular, the merger of photocatalysis with transition metal catalysis and biocatalysis has enabled the discovery of a range of synthetically valuable and hitherto elusive transformations. This has proven exceptionally attractive as highly tunable photocatalysts can selectively generate reactive intermediates from a cadre of abundant, commercially available, native functionalities under mild, biocompatible conditions in an orthogonal manner to traditional thermodynamic processes. For these reasons, this complementary approach has seen widespread adoption in the pharmaceutical, agrochemical, and fragrance industries. This dissertation describes novel applications of the merger of photocatalysis with biocatalysis and transition metal catalysis for the development of powerful synthetic platforms. The second chapter of this thesis outlines a copper metallaphotoredox platform to accomplish a decarboxylative trifluoromethylation of aliphatic carboxylic acids, thereby enabling the late-stage installation of the medicinally relevant moiety. In the third chapter, the development of a photoredox-, HAT-, and organocatalyzed racemization platform is described. Conceptually this demonstrates photocatalysis’ unique ability to generate prochiral radicals at stereocenters traditionally viewed as static. In a collaboration with the Hyster group, we demonstrate that the merger of this platform with enzyme catalysis enables an unprecedented stereoconvergent reaction. Finally, the fourth chapter of this thesis outlines a novel orthogonal approach to converting initial reaction hits into general reactions. This approach applies phenotypic screening techniques and high throughput experimentation to greatly improve the scope and functional group tolerance of the nickel and photoredox dual-catalyzed decarboxylative arylation.