Effective methods for the synthesis of spiro-pyrimidine derivatives through Biginelli-like reaction

The effective synthesis of spiro-pyrimidine derivatives via Biginelli-like reaction was illustrated as follows: The spiropyrrolidindione-pyrimidine derivatives were obtained (mixture of two isomers 50-80%) by using the chiral β-keto-γ-lactams (derived from natural amino acids) with one equivalent of urea and two equivalent of aldehydes. The spirocyclohexyl-pyrimidine derivatives were synthesized via the reaction of cyclohexane-1,3-dione, urea, and aromatic aldehydes in the mole ratio of 1:1:2. The spirodioxane-pyrimidine derivatives were obtained through the four components reaction of Meldrum’s acid with aldehydes and urea. The spiropyrimidindiones-pyrimidine derivatives were synthesized via the four-component reaction of aldehydes (2 equiv), urea, and barbituric acid. The spirooxindole-pyrimidines/quinazoline derivatives were synthesized via three-component Biginelli-like reaction between isatins, acyclic or cyclic 1,3-dicarbonyl compounds and urea/thiourea in one pot and good yields. This review covers the recent greener strategies of spiro pyrimidines based on the Biginelli-like reactions in the 2000–2025 period. This review serves as a guide for synthetic strategies for spiro pyrimidines such as spirooxindole-pyrimidines/quinazolines.