Innovations in Photochemical C-C and C-N Bond Forming Reactions

Abstract

Over the past decade, photoredox catalysis has risen to the forefront of synthetic organic chemistry as an indispensable tool for selective small-molecule activation and chemical-bond formation. New bond forming strategies have the potential to impact a variety of synthetic endeavors including, pharmaceuticals, natural product synthesis, and material sciences. This cutting-edge platform allows photosensitizers to convert visible light into chemical energy, prompting generation of reactive radical intermediates. In particular, the formation of new C−C and C−N bonds is fundamental to organic synthesis. This thesis describes some of our contributions to the design, optimization, implementation, and mechanistic underpinnings of novel C−C and C−N bond forming reactions mediated by photoredox catalysis.

Chapter 1 provides a detailed summary of the importance of photoredox catalysis in organic synthesis and its appeal as an enabling technology for free radical generation. The history. key contributions in the field, the impact of light arrays on reactivity, aliphatic amine functionalization, designing complementary mechanistic paradigms, and applications of photoredox catalysis in industry is reviewed.

Chapter 2 focuses on a method for the radical chlorodifluoromethylation of (hetero)arenes using chlorodifluoroacetic anhydride. A historical perspective on (hetero)arene functionalization via the classic Minisci reaction, along with strategies for radical (perfluoro)alkylation, are presented. Optimization studies, elucidation of scope, and product diversification of chlorodifluoromethylated (hetero)arenes is described.

Chapter 3 describes our efforts in the area of alkene aminoarylation using simple bifunctional arylsulfonylacetamide reagents to synthesize 2,2-diarylethylamines. In this process, single-electron alkene oxidation enables C−N bond formation to provide a key benzylic radical poised for a Smiles-Truce 1,5-aryl shift. This reaction is redox-neutral, exhibits broad functional group compatibility, and occurs at room temperature with loss of sulfur dioxide. The ability of photoredox catalysis to mediate the formation C−C and C−N bonds in a single operation is established in this Chapter.

Chapter 4 continues to explore the utility of bifunctional arylsulfonylacetamide reagents; now in the context of arene dearomatization. Arene dearomatization reactions are an important class of synthetic technologies for the rapid assembly of unique chemical architectures. Here, we describe a catalytic protocol to initiate a carboamination/dearomatization cascade that proceeds through transient sulfonamidyl radical intermediates formed from strong N−H bonds leading to 1,4-cyclohexadiene-fused sultams. Reaction optimization, substrate scope, and mechanistic features of this transformation are presented. Additionally, several new substrate classes are identified which undergo N-radical aryl transfer reactivity with electron-neutral olefins leading to functionalized arylethylamine products in good yields.