REACTIONS OF CYCLIC β-ALKOXYVINYL α-KETO ESTERS WITH HETEROAROMATIC NCC-BINUCLEOPHILES

Authors

  • Oleksandr O. Stepaniuk Enamine Ltd.; Taras Shevchenko National University of Kyiv
  • Bohdan V. Vashchenko Enamine Ltd.; Taras Shevchenko National University of Kyiv
  • Vitalii O. Matvienko Enamine Ltd.
  • Ivan S. Kondratov Enamine Ltd.; V.P. Kukhar Institute of Bioorganic Chemistry & Petrochemistry, NAS of Ukraine
  • Andrey A. Tolmachev Enamine Ltd.; Taras Shevchenko National University of Kyiv
  • Oleksandr O. Grygorenko Enamine Ltd.; Taras Shevchenko National University of Kyiv

DOI:

https://doi.org/10.1007/5632

Keywords:

enone, fused pyridine, isoxazole, lactone, pyrazole, pyrimidine, pyruvate, condensation, regioselectivity.

Abstract

Reactions of five- and six-membered cyclic β-alkoxyvinyl α-keto esters and NCC-binucleophiles are described. The following binucleophiles were studied: heteroaromatic amines (pyrazoles, isoxazole, uracils, and isoquinolinone) and 2-(benzimidazolyl)acetonitrile. It was found that condensation proceeded regioselectively in the case of five-membered cyclic enone. Fused α-pyridine carboxylates, likely formed in situ, underwent lactonization, which resulted in six-membered lactones in moderate to excellent yields (53–91%). Only in the
case of 3-unsubstituted 5-aminopyrazole, formation of γ-pyridine carboxylate followed by cyclization to isomeric lactone was observed. On the contrary, six-membered cyclic enone was reactive only toward heterocyclic amines under optimized conditions and provided open-chain α-pyridine carboxylates in 40–80% yield.

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Published

2020-04-01

Issue

Vol. 56 No. 3 (2020)

Section

Original Papers