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Synthesis 2006(4): 659-665  
DOI: 10.1055/s-2006-926291
PAPER
© Georg Thieme Verlag Stuttgart · New York

Catalyst-free, High-yield, and Stereospecific Synthesis of 3-Phenylthio β-Lactam Derivatives

Lei Jiao, Yong Liang, Qianfeng Zhang, Shiwei Zhang, Jiaxi Xu*
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P. R. of China
Fax: +86(10)62751708; e-Mail: jxxu@pku.edu.cn;
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Publication History

Received 26 July 2005
Publication Date:
11 January 2006 (online)

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Abstract

α-Diazocarbonyl compounds are good precursors of ketenes in the Staudinger reaction. On the basis of the reactions of S-phenyl diazothioacetate with imines under the catalysis of Rh2(OAc)4 a method for the synthesis of 3-phenylthio β-lactam derivatives has been developed previously. In this paper, a more convenient and improved procedure was achieved, which simplified the synthesis of S-phenyl diazothioacetate and made the reaction work well without the expensive Rh2(OAc)4 catalyst. The catalyst-free reactions of S-phenyl diazothioacetate with a variety of imines produced monocyclic and polycyclic β-lactams stereospecifically in good to excellent yields.

Key words

catalyst-free - imine - β-lactam - S-phenyl diazothioacetate - Staudinger reaction

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12

We also attempted chiral Rh(II) and Cu(I) complexes as catalysts (Figure [2] ), hoping to achieve the asymmetric ketene-imine reaction. However, in all cases, the ee of the product 3a was 0%, though the yields were quite good (>90%).

13

The relative configurations of β-lactams 3a-d were determined by the coupling constants between the protons at C-3 and C-4 of the β-lactam rings (J C-3,C-4 = 2.1-2.7 Hz for trans-β-lactams; J C-3,C-4 = 5.4 Hz for cis-β-lactams).

15

The Rh2(OAc)4 catalyzed reactions of 1 with 2g, 2h, and 2l were also conducted, and the yields of β-lactam derivatives 3g, 3h, and 3l are 96%, 97%, and 99%, respectively. This indicates that for complex cyclic imines the transition metal-catalyzed reactions are better than catalyst-free reactions due to the lower reaction temperature, which is appropriate for thermally sensitive substrates.

16

CCDC 277470 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax:+44 (1223)336033.