Chiral fluoroacetic acid: synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate in high enantiopurity

Rudy D. P. Wadoux, Xiaowei Lin, Neil S. Keddie, David O'Hagan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

A two-step synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate (sodium salts) in high enantioselectivity is reported. The synthesis is the development of a previous one in which the enantioselectivity has been increased from similar to 38% ee to >95% ee. The improvement in enantioselectivity applied Bio's methodology, which involved a deoxyfluorination reaction with DAST on either enantiomer of [H-2(1)]-benzyl alcohol, adding TMS-morpholine to the reaction. The additive promotes an S(N)2 inversion process, and suppresses a competing non-stereospecific S(N)1 reaction course, and as a result significantly improves the stereointegrity of the C-F bond formation. The intermediate [H-2(1)]-benzyl alcohols, [H-2(1)]-benzyl fluorides and the product [H-2(1)]-fluoroacetates as their hexyl esters were separately assayed for their stereochemical integrity, using the Courtieu method. This method involved measuring their H-2 NMR spectra in a chiral matrix of poly-gamma-benzyl L-glutamate. The chiral assay demonstrated that there was no significant loss in stereointegrity during the deoxyfluorination reaction and showed that the enantiomers of [H-2(1)]-fluoroacetate were generated with high enantiomeric purity (95% ee). (C) 2013 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)719-723
Number of pages5
JournalTetrahedron: Asymmetry
Volume24
Issue number12
DOIs
Publication statusPublished - 30 Jun 2013

Keywords

  • DEUTERIUM NMR
  • STREPTOMYCES CATTLEYA
  • ENANTIOMERIC ANALYSIS
  • FLUORINATION

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