1,2-Dihydropyrimidine synthesis <i>via</i> titanium-mediated multicomponent coupling of alkynes, nitriles, and aldehydes.

ABSTRACT: While dihydropyrimidine cores are found in a number of bioactive molecules, 1,2-dihydropyrimidine regioisomers remain relatively underexplored due to a scarcity of simple synthetic routes to access them. Here, a modular, multicomponent synthesis to 1,2-dihydropyrimidines from alkynes, nitriles, aldehydes, and Ti imido complexes is reported, proceeding through a key diazatitanacycle intermediate that was previously exploited for pyrazole and α-diimine synthesis. The 1,2-dihydropyrimidines are formed through [2+2]-cycloaddition of an aldehyde with the diazatitanacycle synthetic intermediate, followed by cycloreversion to a 1,5-diazatriene that undergoes facile electrocyclization to the 1,2-dihydropyrimidine.

SUBMITTER: Dunscomb RJ 

PROVIDER: S-EPMC12151746 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature