Studies on photoinduced site-selective functionalizations of heteroarenes using hydrogen atom transfer strategies

Abstract

Part 1. Visible Light-Induced Synthesis of Spiroepoxy Chromanone Derivatives via a Tandem Oxidation/Radical Cyclization/Epoxidation Process A straightforward approach for synthesizing spiroepoxy chroman-4-one derivatives was developed with excellent levels of efficiency through visible light-enabled tandem radical strategy. The reaction is initiated by formation of the acyl radical which undergoes internal radical cyclization and epoxidation. Furthermore, this method was able to extend to a three-step tandem reaction starting with benzyl alcohol. This unprecedented tandem approach utilizes a broad range of substrates, providing a convenient and powerful synthetic tool for accessing spiroepoxy chroman-4-one and their nitrogen-containing derivatives, that have high synthetic utility.

Part 2. Site-Selective C–H Acylation of Pyridinium Derivatives by Photoredox Catalysis A new strategy for visible-light-induced site-selective C–H acylation of pyridinium salts was developed by employing N-methoxy- or N-aminopyridinium salts, offering a powerful synthetic tool for accessing highly valuable C2- and C4-acylated pyridines. The methoxy or amidyl radicals photocatalytically generated from the pyridinium salts can undergo hydrogen atom abstraction from readily available aldehydes to form acyl radicals, which can engage in addition to pyridinium substrates. Remarkably, the use of N-methoxypyridinium salts preferentially gives the C2-acylated pyridines, and the site selectivity can be switched from C2 to C4 by using N-aminopyridinium salts. The utility of this transformation was further demonstrated by the late-stage functionalization of complex biorelevant molecules and by application of acyl radicals photocatalytic radical cascades.

Part 3. Visible Light-Driven C4-Selective Alkylation of Pyridinium Derivatives with Alkyl Bromides A general strategy for the photochemical cross-coupling between N-amidopyridinium salts and various alkyl bromides under catalyst-free conditions was developed, granting facile access to valuable C4-alkylated pyridines. This approach exploits the intriguing photochemical activity of electron donor-acceptor (EDA) complexes between N-amidopyridinium salts and bromide, which provides a photoactive handle capable of generating silyl radicals and driving the alkylation process. This photochemical alkylation protocol obviates the need for an external photocatalyst, features a broad substrate scope, and is highly C4-selective. The robustness of this protocol was further demonstrated by the late-stage functionalization of complex pyridine-containing compounds under mild and metal-free conditions.