An environmentally benign cascade reaction of chromone-3-carboxaldehydes with ethyl 2-(pyridine-2-yl)acetate derivatives for highly site-selective synthesis of quinolizines and quinolizinium salts in water

Abstract

A novel protocol for the synthesis of quinolizines (3) and quinolizinium salts (4) from chromone-3-carboxaldehydes 1 with ethyl 2-(pyridine-2-yl)acetate derivatives 2via an unprecedented cascade reaction in water was constructed. As a result, functionalized quinolizines (3) bearing a chromone skeleton were prepared by simple reflux of the mixture of chromone-3-carboxaldehydes with ethyl 2-(pyridine-2-yl)acetate derivatives in water. Quinolizinium salts (4) were also prepared in water under acidic conditions. The formation of quinolizinium salts was accompanied by the formation of two bonds and the cleavage of one bond in a single step. This protocol can be used in the synthesis of a wide variety of quinolizines and quinolizinium salts, and is suitable for combinatorial and parallel syntheses of quinolizine derivatives natural-like products. 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), excellent yields (83–96%), and formation of a product with potential biological activity.