Photoinduced Carbon Radical-Mediated C-H Functionalization and Cascade Reactions by Pyridine N-oxide

Abstract

Pyridine N-oxides and their derivatives are readily available and highly versatile reagents that have attracted significant attention in organic synthesis. Chapter One first reviews the applications of pyridine N-oxides in traditional two-electron chemistry, such as applications as oxidants, ligands for metal complexes and organocatalysts. However, investigations of unconventional single-electron transfer chemistry of pyridine N-oxides in synthesis and catalysis has long been overlooked until recently. The second section of Chapter One focuses on the recent synthetic development in single-electron transfer chemistry of pyridine N-oxides via the enabling technology of modern photoredox catalysis and photochemistry, including the applications of pyridine N-oxides 1) in the development of visible light-promoted β-oxyvinyl radical generation and corresponding cascade reactions and 2) photoinduced selective C-H functionalization by pyridine N-oxide based hydrogen atom transfer (HAT) catalysis. In Chapter Two, the development of easily accessible pyridine N-oxide derivatives as efficient photoinduced HAT catalysts for selective C–H functionalizations is presented. This method is efficient for a wide range of C-H functionalization and exhibited remarkable versatility. This study further demonstrates that catalyst-controlled site selectivity of C–H functionalization is possible upon alterating the steric structure of pyridine N-oxides. In Chapter Three, the synthetic utility of photocatalytically generated β-oxyvinyl radical from 1,6-enynes and pyridine N-oxides are demonstrated in developing divergent radical cascade annulation reactions. By using an acridinium photocatalyst and 2,6-lutidine N-oxide as a source of oxygen-centered radical, various 1,6-enynes, including oxygen-tethered and nitrogen-tethered ones, 1-allyl-2-ethynylbenzenes, were suitable substrates for producing a series of tetrahydroindeno[2,1-c]pyran-4-ones, tetrahydroindeno[2,1-c]pyridin-4-ones, and 1H-cyclopropa[b]naphthalen-2(1aH)-ones in good to high yields with high diastereoselectivties. In Chapter Four, a photoinduced selective hydroamination of ynamides with nitrogen heteroaromatic nucleophiles is disclosed by using an organocatalytic photoredox system; a direct method to construct a diverse of (Z)-α-azole enamides from ynamides and pyrazoles, as well as triazoles, benzotriazoles, indazoles, and tetrazoles, is developed.