Access to Seleno-Functionalized Thiazolo[3,2-a]Pyrimidinones and Pyrimido[2,1-b][1,3]Thiazinones via Selenocyclization of 2-Alkenylthiopyrimidinones and Their Fused Analogs

The methodology of electrophilic selenylation/cyclization of 2-alkenylthiopyrimidinones and their fused analogs underlies most of the reported synthetic approaches to seleno-functionalized thiazolo[3,2-a]pyrimidinones and pyrimido[2,1-b][1,3]thiazinones. We have developed a novel implementation of this strategy using as reagent phenylselenyl chloride or the visible-light-induced radical-generating (PhSe)(2)/CBr4 system. The effect of the unsaturated substrate structure and reaction conditions on the selenocyclization regioselectivity has been revealed and analyzed in detail. It has been established that regardless of the conditions used, 2-allylthiopyrimidinones react with selenylating agents via electrophilic 5-exo-trig cyclization mainly involving the N1 nitrogen atom to give selenium-containing thiazolo[3,2-a]pyrimidinones as major products. On the contrary, the selenocyclization with 2-cinnamylthiopyrimidinones is dominated by the 6-endo-trig mode: it mostly involves six-membered ring closure at the N1 or N3 atom thus leading to selenylated pyrimido[2,1-b][1,3]thiazinones, with the regiochemistry governed by the position and nature of the substituents on the substrate pyrimidine ring. However, some of the fused cinnamylthio-substituted substrates yield 5-exo-trig cyclized products in the LiClO4/& Mcy;& iecy;NO2 system (a sufficiently polar solvent with a strong electrolyte added).