Categories: Synthesis of N-Heterocycles > Lactams >

Synthesis of β-lactams

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Recent Literature

Preferential Rh(II) carbenoid intramolecular C-H versus O-H insertion derived from α-diazo-acetamides can be achieved in water by creating a large hydrophobic environment around the reactive carbenoid center using an appropriate combination of the catalyst and amide groups.
N. R. Candeias, P. M. P. Gois, C. A. M. Afonso, J. Org. Chem., 2006, 71, 5489-5497.

N-Tosyl-3-halo-3-butenylamines underwent efficient Ullmann-type coupling to afford 2-alkylideneazetidines, which could be readily converted to the corresponding β-lactams by oxidation with O₃.
H. Lu, C. Li, Org. Lett., 2006, 8, 5365-5367.

A catalytic enantioselective Staudinger reactions is described that preferentially furnish trans β-lactams. The use of an N-triflyl protecting group for the imine is crucial for the success of the reaction.
E. C. Lee, B. L. Hodous, E. Bergin, C. Shih, G. C. Fu, J. Am. Chem. Soc., 2005, 127, 11586-11587.

The Staudinger synthesis, an overall [2 + 2] cycloaddition of a ketene with an imine, provides a nicely convergent route to biologically and synthetically interesting β-lactams. A planar-chiral derivative of 4-(pyrrolidino)pyridine serves as a very effective enantioselective catalyst coupling a range of symmetrical and unsymmetrical ketenes with various imines with very good stereoselection and yield.
B. L. Hodous, G. C. Fu, J. Am. Chem. Soc., 2002, 124, 1578-1579.

The transformation of diazoketones to ketenes can be realized not only by utilizing photochemical reaction conditions but also under the action of microwave irradiation. In the presence of imines, the generated ketenes react further to afford β-lactams. Various trans-substituted β-lactams derived from amino acids have been prepared.
M. R. Linder, J. Podlech, Org. Lett., 2001, 3, 1849-1851.

A practical methodology for the catalytic, asymmetric synthesis of β-lactams results from the development of a catalyzed reaction of ketenes (or their derived zwitterionic enolates) and imines using benzoylquinine as chiral catalyst and proton sponge as the stoichiometric base.
A. E. Taggi, A. M. Hafez, H. Wack, B. Young, D. Ferraris, T. Lectka, J. Am. Chem. Soc., 2002, 124, 6626-6635.