A 3 + 1 + 2 annulation strategy for the modular synthesis of polysubstituted pyridines, such as 2,6-diarylnicotinic acid esters and nicotinonitriles, is described. Multicomponent reactions employ β-enamine esters/β-enamine nitriles and aromatic aldehydes as starting materials, and calcium carbide as a source of alkyne. The key advantages of this method include the use of an inexpensive and easy-to-handle solid alkyne source instead of flammable and explosive gaseous acetylene, a broad substrate scope with good functional group tolerance, high yield, operational simplicity, and scalability to the gram scale.
Wang et al. (Wed,) studied this question.