EXPANDING THE CHEMICAL SPACE OF <i>sp</i>3-ENRICHED 4,5-DISUBSTITUTED OXAZOLES <i>v</i>ia SYNTHESIS OF NOVEL BUILDING BLOCKS

Authors

  • Evgeniy Y. Slobodyanyuk Enamine Ltd. Institute of Organic Chemistry, National Academy of Sciences of Ukraine
  • Andrii A. Andriienko Enamine Ltd. Taras Shevchenko National University of Kyiv
  • Bohdan V. Vashchenko Enamine Ltd. Taras Shevchenko National University of Kyiv
  • Dmitriy M. Volochnyuk Enamine Ltd. Institute of Organic Chemistry, National Academy of Sciences of Ukraine
  • Sergey V. Ryabukhin Enamine Ltd. Taras Shevchenko National University of Kyiv
  • Oleksandr O. Grygorenko Enamine Ltd. Taras Shevchenko National University of Kyiv

DOI:

https://doi.org/10.1007/4991

Keywords:

alcohols, amines, azides, chlorides, esters, oxazoles, sulfonyl chlorides, building blocks.

Abstract

An efficient approach to the preparation of novel sp3-enriched 4,5-disubstituted oxazoles bearing a functional group at the C-4 position is described. The method commenced with synthesis of ethyl oxazole-4-carboxylates (13 examples, 63–99% yield), with subsequent function insertion to the heterocyclic core by late-stage functional group transformation. The LiBH4-mediated reduction of ethyl oxazole-4-carboxylates was the only method which could be optimized at multigram scale (up to 40 g), and its scope was demonstrated by preparation of 13 alcohols with (cyclo)alkyl, fluoroalkyl, or N-Boc-aminoalkyl moiety at the C-5 position (47–89% yield). The utility of these key intermediates was demonstrated by the preparation of chlorides (13 examples, 90–99% yield), azides (13 examples, 83–99% yield), amines (13 examples, 80–98% yield), and sulfonyl chlorides (4 examples, 68–97% yield) – advanced building blocks for synthetic and medicinal chemistry.

 

Published

2019-05-22