Beilstein Journal of Organic Chemistry (Jun 2011)

Single enantiomer synthesis of α-(trifluoromethyl)-β-lactam

  • Václav Jurčík,
  • Alexandra M. Z. Slawin,
  • David O'Hagan

DOI
https://doi.org/10.3762/bjoc.7.86
Journal volume & issue
Vol. 7, no. 1
pp. 759 – 766

Abstract

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The first synthesis of α-(trifluoromethyl)-β-lactam ((S)-1) is reported. The route starts from α-(trifluoromethyl)acrylic acid (2). Conjugate addition of α-(p-methoxyphenyl)ethylamine ((S)-3b), generated an addition adduct 4b which was cyclised to β-lactam 5b. Separation of the diastereoisomers by chromatography gave ((αS,3S)-5b). N-Debenzylation afforded the desired α-(trifluoromethyl)-β-lactam ((S)-1). The absolute stereochemistry of diastereoisomers 5 was determined by X-ray crystallographic determination of a close structural analogue, (αS,3S)-5c, and then 1H and 19F NMR correlation to the individual diastereoisomers of 5a and 5b.

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