An environmentally benign multi-component reaction: Highly regioselective synthesis of functionalized 2-(diarylphosphoryl)-1,2-dihydro-pyridine derivatives

Abstract

A novel protocol was developed for the construction of highly functionalized 2-(diarylphosphoryl)-1,2-dihydropyridine derivatives (DAPDHPs) from 3-formylchromones (1), heterocyclic ketene aminals (HKAs, 2), and phosphine oxides (R2P(O)H, 3) via a novel, one-pot cascade reaction. Optimization of the reaction conditions determined that refluxing the mixture of the 3-formylchromones, HKAs, and various R2P(O)H in propylene carbonate (PC) in the presence of triethylamine as a base facilitated the highest yields of the DAPDHP products. This cascade reaction, which involved the cleavage of one C–O bond in the 3-formylchromone substrates and the formation of three new bonds (one C–C, one C–N, and one C–P bond), enabled the synthesis of a small library of DAPDHP products. The dearomatized DAPDHP products were formed by the regioselective nucleophilic addition of the R2P(O)H reagents to the intermediate pyridinium salts 8. This approach has several advantages such as the use of an environmentally-friendly solvent, simple and practical operation (with filtration and washing without column chromatography separation), good yields, and a product with potential biological activity.

Keywords

• 2-(Diarylphosphoryl)-1,2-dihydropyridine
• Cascade reaction
• Selective synthesis
• NHeterocyclic ketene aminals