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

Beilstein Journal of Organic Chemistry. 2011;7(1):759-766 DOI 10.3762/bjoc.7.86

 

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Journal Title: Beilstein Journal of Organic Chemistry

ISSN: 1860-5397 (Online)

Publisher: Beilstein-Institut

LCC Subject Category: Science: Chemistry: Organic chemistry

Country of publisher: Germany

Language of fulltext: English

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AUTHORS

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

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Time From Submission to Publication: 17 weeks

 

Abstract | Full Text

The first synthesis of &#945;-(trifluoromethyl)-&#946;-lactam ((<i>S</i>)-<b>1</b>) is reported. The route starts from &#945;-(trifluoromethyl)acrylic acid (<b>2</b>). Conjugate addition of &#945;-(<i>p</i>-methoxyphenyl)ethylamine ((<i>S</i>)-<b>3b</b>), generated an addition adduct <b>4b</b> which was cyclised to &#946;-lactam <b>5b</b>. Separation of the diastereoisomers by chromatography gave ((&#945;<i>S,</i>3<i>S</i>)-<b>5b</b>). N-Debenzylation afforded the desired &#945;-(trifluoromethyl)-&#946;-lactam ((<i>S</i>)-<b>1</b>). The absolute stereochemistry of diastereoisomers <b>5</b> was determined by X-ray crystallographic determination of a close structural analogue, (&#945;<i>S,</i>3<i>S</i>)-<b>5c</b>, and then <sup>1</sup>H and <sup>19</sup>F NMR correlation to the individual diastereoisomers of <b>5a</b> and <b>5b</b>.