Mechanochemical Regioselective [3+3] Annulation of 6-Amino Uracil with Propargyl Alcohols Catalyzed by a Brønsted Acid/Hexafluoroisopropanol.

A mechanochemistry approach is developed for regioselective synthesis of functionalized dihydropyrido[2,3-d]pyrimidines by milling propargylic alcohols and 6-aminouracils with HFIP/p-TsOH. In the case of tert-propargyl alcohols, this [3+3] cascade annulation proceeded through allenylation of uracil followed by a 6-endo trig cyclization. With sec-propargyl alcohols, the reaction furnished the propargylation of uracil.