Development of acylation reactions using radicals derived from pyridinium salts

Abstract

(Part 1. Visible-Light-Induced Site-Selective C-H Acylation of N-Substituted Pyridinium Salts) A powerful strategy for photocatalytic site-selective C-H acylation of pyridine derivates was developed by changing radicals generated from N-substituted pyridinium salts. From this convenient method, we can get the highly valuable C2 and C4-selective acylated pyridines easily. By photocatalytic system, the methoxy and amidyl radicals are generated. They abstract hydrogen atom from aldehyde substrates and generate acyl radicals reacted with pyridinium substrates. The use of N-aminopyridinium salts gives the C4-selective acylated pyridine products and N-alkoxypyridinium salts generates the C2-selective acylated pyridines. Demonstrated substrate scopes show us very broad application potentials of this reaction and this strategy also can be applied to radical cascade cyclization and photocatalytic cascade construction. (Part 2. N-Heterocyclic Carbene-Catalyzed Deaminative Acylation by Pyridinium Salts) The first example of N-heterocyclic carbene (NHC)-catalyzed deaminative acylation by radical-radical coupling strategy reacted alkyl radical generated from Katritzky salt with NHC-induced ketyl radical species was developed. The redox-active Katritzky pyridinium salts for investigating the utility of amine part of amino-acid scaffolds were used. Our mild condition method is very useful for obtaining highly utilitized ketone moieties from amine group of amino-acid derivatives. NHC was used as a catalyst for occurring single electron transfer (SET) of the Katritzky salt to generate alkyl radical. And the Katritzky alkyl pyridinium salts derived from amino acid scaffolds showed a broad scope tolerance under this reaction condition. The Breslow intermediate generated from coupling of the NHC and aldehyde become a ketyl radical via SET event. And this ketyl radical reacts with alkyl radical generated from pyridinium salts and finally, the acylated product is obtained.