Beilstein Journal of Organic Chemistry (Jun 2011)
Single enantiomer synthesis of α-(trifluoromethyl)-β-lactam
Abstract
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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