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

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

References

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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%).

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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).

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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.

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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 [e-mail], or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax:[phone].