Multi-component cascade reaction of 3-formylchromones: highly selective synthesis of 4,5-dihydro-[4,5′-bipyrimidin]-6(1H)-one derivatives

Abstract

A novel protocol for the construction of highly functionalized bipyrimidine derivatives 4 and 5 from 3-formyl-chromones, ethyl 2-(pyridine-2-yl)acetate derivatives, and amidine hydrochlorides via an interesting and considerably complex multi-component cascade reaction was developed. The cascade reaction was manifested by refluxing a mixture of the three substrates in acetonitrile or DMF along with Cs₂CO₃. A series of 4,5-dihydro-[4,5′-bipyrimidin]-6(1H)-ones (DBPMOs) 4 was constructed regioselectively in suitable to excellent yields. Moreover, intermediates 4 then underwent a novel, metal- and oxidant-free cascade reaction to produce a series of [4,5′-bipyrimidin]-6(1H)-ones (BPMOs) 5. The formation of the bipyrimidine derivatives 4–5 was enabled by the formation of five bonds and the cleavage of one bond in one pot. This protocol can be used in the synthesis of functionalized bipyrimidine derivatives via a multi-component one-pot cascade reaction rather than multi-step reactions, which is suitable for both combinatorial and parallel syntheses of bipyrimidine derivatives.