Single enantiomer synthesis of alpha-(trifluoromethyl)-beta-lactam

Vaclav Jurcik; Alexandra M. Z. Slawin; David O'Hagan

doi:10.3762/bjoc.7.86

Single enantiomer synthesis of alpha-(trifluoromethyl)-beta-lactam

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Abstract

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

Original language	English
Pages (from-to)	759-766
Number of pages	8
Journal	Beilstein Journal of Organic Chemistry
Volume	7
DOIs	https://doi.org/10.3762/bjoc.7.86
Publication status	Published - 6 Jun 2011

Keywords

Enantiomeric resolution
Erganofluorine building blocks
Alpha-(trifluoromethyl)-beta-lactam

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10.3762/bjoc.7.86

5397-7-86
© 2011 Jurčík et al; licensee Beilstein-Institut. This is an Open Access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (http://www.beilstein-journals.org/bjoc)
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title = "Single enantiomer synthesis of alpha-(trifluoromethyl)-beta-lactam",

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

keywords = "Enantiomeric resolution, Erganofluorine building blocks, Alpha-(trifluoromethyl)-beta-lactam",

author = "Vaclav Jurcik and Slawin, \{Alexandra M. Z.\} and David O'Hagan",

year = "2011",

month = jun,

day = "6",

doi = "10.3762/bjoc.7.86",

language = "English",

volume = "7",

pages = "759--766",

journal = "Beilstein Journal of Organic Chemistry",

issn = "1860-5397",

publisher = "Beilstein-Institut Zur Forderung der Chemischen Wissenschaften",

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TY - JOUR

T1 - Single enantiomer synthesis of alpha-(trifluoromethyl)-beta-lactam

AU - Jurcik, Vaclav

AU - Slawin, Alexandra M. Z.

AU - O'Hagan, David

PY - 2011/6/6

Y1 - 2011/6/6

N2 - The first synthesis of alpha-(trifluoromethyl)-beta-lactam ((S)-1) is reported. The route starts from alpha-(trifluoromethyl)acrylic acid (2). Conjugate addition of alpha-(p-methoxyphenyl)ethylamine ((S)-3b), generated an addition adduct 4b which was cyclised to beta-lactam 5b. Separation of the diastereoisomers by chromatography gave ((alpha S,3S)-5b). N-Debenzylation afforded the desired alpha-(trifluoromethyl)-beta-lactam ((S)-1). The absolute stereochemistry of diastereoisomers 5 was determined by X-ray crystallographic determination of a close structural analogue, (alpha S,3S)-5c, and then H-1 and F-19 NMR correlation to the individual diastereoisomers of 5a and 5b.

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

KW - Enantiomeric resolution

KW - Erganofluorine building blocks

KW - Alpha-(trifluoromethyl)-beta-lactam

U2 - 10.3762/bjoc.7.86

DO - 10.3762/bjoc.7.86

M3 - Article

SN - 1860-5397

VL - 7

SP - 759

EP - 766

JO - Beilstein Journal of Organic Chemistry

JF - Beilstein Journal of Organic Chemistry

ER -

Single enantiomer synthesis of alpha-(trifluoromethyl)-beta-lactam

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