Construction of carbon-nitrogen bond and regioselective pyridine functionalization via visible‐light photocatalysis

Abstract

The Visible-light photocatalysis has a completely different reactivity and regio-selectivity than ground-state catalysis. In this dissertation, visible-light photocatalyzed reactions generating a nitrogen-centered radical to form a carbon-nitrogen bond and to enable regio-selective pyridylation are introduced. The reactions introduced in this paper are presented as follows. 1) A synthetic route to construct quinolinone derivatives via oxidative C−H amidation was developed. In this transformation, amidyl radicals are generated by homolysis of the N−H bond of amide precursors via proton-coupled electron-transfer under blue LED illumination, which leads to oxidative intramolecular C−H amidation. 2) A photocatalytic strategy for alkene aminopyridylation was developed using N-aminopyridinium salts as both aminating and pyridylating reagents. Amino and pyridyl groups are simultaneously incorporated into alkenes with complete regioselectivity. In this process, the capacity for controlling C-4 regioselectivity in the radical trapping step could be rationalized by steric and electronic properties of the N-aminopyridinium salt using several control experiments and DFT based computational studies. 3) A visible-light-induced ortho-selective aminopyridylation of alkenes via radical-mediated 1,3-dipolar cycloaddition was developed by utilizing an underexplored reactivity mode of N-aminopyridinium ylides. The photocatalyzed single-electron oxidation of N-aminopyridinium ylides generates the corresponding radical cations that enable previously inaccessible 1,3-cycloaddition with a broader range of alkene substrates. The resulting cycloaddition adducts rapidly undergo subsequent homolytic cleavage of the N–N bond, conferring a substantial thermodynamic driving force to yield various β-aminoethyl pyridines. Remarkably, amino and pyridyl groups can be installed into both activated and unactivated alkenes with modular control of ortho-selectivity and 1,2-syn-diastereoselectivity under metal-free and mild conditions. Combined experimental and computational studies are conducted to clarify the detailed reaction mechanism and the origins of site-selectivity and diastereoselectivity.