Assembly of polysubstituted fused pyrimidines via hetero-Diels-Alder [4 + 2] cycloaddition of 1,3-bisnucleophiles, aldehydes and ammonium acetate: a green synthetic approach.

A modular, metal-free multicomponent cascade reaction protocol has been developed for the synthesis of pyrazole-/isoxazole-/chromene-fused pyrimidines from 1,3-bisnucleophiles, aldehydes, and NH4OAc under neat reaction conditions. This protocol involves the in situ generation of diene and dienophile and subsequent reaction via hetero-Diels-Alder-type [4 + 2] cycloaddition followed by aerial oxidation, which leads to the title products with the formation of one C-C and three C-N bonds. The advantages of this green synthetic method are its simple reaction conditions, readily available substrates, and excellent yields even at gram-scale synthesis.