A straightforward synthesis of 2-[1-alkyl-5,6-bis(alkoxycarbonyl)-1,2,3,4- tetrahydro-2-oxopyridin-3-yl]acetic acid derivatives via domino Michael addition-cyclization reaction

摘要

A new and efficient synthesis of 2-[1-alkyl-5,6-bis(alkoxycarbonyl)-1,2,3, 4-tetrahydro-2-oxopyridin-3-yl]acetic acid derivatives by a one-pot three-component reaction between primary amine, dialkyl acetylenedicarboxylate, and itaconic anhydride (=3,4-dihydro-3-methylidenefuran-2,5-dione) is reported. The reaction was performed without catalyst and under solvent-free conditions with excellent yields. Notably, the ready availability of the starting materials, and the high level of practicability of the reaction and workup make this approach an attractive complementary method to access to unknown 2-[1-alkyl-5,6-bis(alkoxycarbonyl)-1,2,3,4-tetrahydro-2-oxopyridin-3-yl]acetic acid derivatives. The structures were corroborated spectroscopically (IR, ~1H- and ~(13)C-NMR, and EI-MS) and by elemental analyses. A plausible mechanism for this type of domino Michael addition-cyclization reaction is proposed (Scheme 2).