Direct Construction of High-Value Pyridine Scaffolds through Manganese-Promoted Alkene Dicarbofunctionalization

Abstract

The direct construction of high-value pyridine scaffolds through manganese-catalyzed alkene dicarbofunctionalization starting from ubiquitous carbonyls and heterocyclic compounds is reported. This protocol provides an efficient platform for constructing a wide array of γ-heterocyclic ketone derivatives, which are useful bioactive scaffolds, with high atom economy and controlled regioselectivity. An intramolecular approach was also developed to efficiently synthesize α-tetralones, tetrahydroquinolines, and benz[h]isoquinolines which have garnered significant attention due to their potential applications in medicinal chemistry but also in materials science. In addition, a complementary electrochemical protocol has also been developed to avoid the use of stoichiometric amounts of Mn(III)-salts. Finally, several control experiments allowed for a proposed mechanism to be assembled thus rationalizing the crucial role of N-methoxypyridinium salts.