Photocatalyzed pyridylation of C($sp^3$)–H bonds using pyridinium salts

Abstract

Part 1. Bifunctionalization of Alkenes Using Pyridinium Salts

$\beta$-Pyridylphosphine derivatives consisting of vicinal pyridine and phosphine group possess soft $\pi$-acceptor properties of phosphines and hard $\sigma$-donor features of pyridines, which are widely employed as ligands in various transition metal complexes. An efficient synthetic method for the construction of $\beta$-pyridylalkylphosphonates was developed via a one-pot three-component reaction between P(O)–H compounds, alkenes and N-heteroarenium salts under mild conditions. The reaction is thought to occur by the addition of a phosphonyl radical to the alkene to form alkyl radical intermediate, which goes on to add to the N-methoxypyridinium salt. This straightforward methodology is applied to a variety of N-heteroarenium salts and alkene substrates to prepare various synthetically and biologically important $\beta$-pyridylalkylphosphonates groups.

Part 2. Metal-Free Visible-Light-Induced Pyridylation of Remote C($sp^3$)–H Bonds Using Pyridinium Salts

2.1 Pyridylation of remote C($sp^3$)–H bonds using N-alkoxypyridinium salts

Direct C($sp^3$)–H functionalization has been recognized as a powerful tool for various carbon–carbon or carbon–heteroatom bond formation. We introduced a metal-free, visible-light-induced site-selective pyridylation of remote C($sp^3$)–H bonds. The new designed N-alkoxypyridinium salts can serve as both alkoxy radical precursors and pyridiyl sources. The alkoxy radical can be generated via the single electron transfer of an N-alkoxypyridinium substrates by a photoexcited quinolinone catalyst. Subsequent radical translocation of the alkoxy radical forms a nucleophilic alkyl radical intermediate, which undergoes addition to the substrate to achieve remote C($sp^3$)–H pyridylation. This cascade strategy provides a powerful platform for remote C($sp^3$)–H heteroarylation in a controllable and selective manner and is well suited for late-stage functionalization of complex bioactive molecules.

2.2 Pyridylation of C($sp^3$)–H bonds using N-aminopyridinium salts

The direct functionalization of C($sp^3$)–H bonds constitutes a powerful and atom-economic approach for the bond formation. Radical translocation processes mediated by heteroatom radicals provide a potential platform for the selective functionalization of remote inert C($sp^3$)–H bonds. We were intrigued by the possibility of developing efficient pathway of remote C($sp^3$)–H bond functionalization by translocation of N-centered radical, introducing pyridinium salt substrate system. The efficient site-selective pyridylation of remote C($sp^3$)–H bonds using N-aminopyridinium salts via photocatalysis was developed. This strategy involves the generation of radical species from pyridinium salts, 1,5-HAT process, and pyridylation to produce C-4 alkylation products. The possibility of α-amino functionalization and cyclization was also observed, and various divergent reactions of N-aminopyridinium salts are under investigation.