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Synthesis 2006(2): 227-230  
DOI: 10.1055/s-2005-924765
PAPER
© Georg Thieme Verlag Stuttgart · New York

Enantiospecific Formation of 3,6-Dihydro-1H-pyridin-2-ones: Low-Pressure Palladium-Catalysed Decarboxylative Carbonylation of 3-Tosyl-5-vinyloxazolidin-2-ones

Julian G. Knight*a, Iain M. Lawsona, Christopher N. Johnsonb
a School of Natural Sciences, Chemistry, Bedson Building, University of Newcastle-Upon-Tyne, Newcastle-Upon-Tyne, NE1 7RU, UK
Fax: +44(191)2227068; e-Mail: J.G.Knight@ncl.ac.uk;
b GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK
Further Information

Publication History

Received 16 September 2005
Publication Date:
21 December 2005 (online)

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Abstract

Palladium-catalysed decarboxylative carbonylation of 3-tosyl-5-vinyloxazolidin-2-ones 5 occurs at atmospheric pressure to give 1-tosyl-3,6-dihydro-1H-pyridin-2-ones 6. The reaction proceeds with no loss of enantiopurity and detosylation with sodium naphthalenide gives the title compounds in good yields.

Key words

carbonylation - catalysis - palladium - cyclisation - lactams

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9

The 1H NMR spectrum of the crude product mixture showed no evidence of β-lactam formation (in particular, no signals in the range 3.5-4 ppm for the azetidinone 3- and 4-protons); see also ref. 8.

12

Gas chromatography analysis [138 °C, β-dextrin 120 column (20 m × 0.25 mm)] of (6R)-3,6-dihydro-6-isopropyl-1H-pyridin-2-one (6R)-2a, formed by the direct carbonylation of (4R)-1a, showed a single peak (t R 36.963 min). Likewise, analysis of (6R)-2a formed by deprotection of the N-tosylpiperidinone (4R)-6a also showed only one peak (t R 36.703 min), as did the analysis of the (S)-N-H lactam (6S)-2a (t R 37.856 min). Analysis of a 1:4 mixture of the enantiomers, (6R)-2a/(6S)-2a showed two peaks in a 1:4 ratio (37.747 min; 38.590 min).