[2 + 2] Cycloaddition reactions between ketenes, bearing amino‐, oxy‐, or halo‐ groups, and imines are recognized as being amongst the most important and direct routes to β‐lactams. Alkyl‐substituted ketenes also furnished the corresponding β‐lactams upon reaction with activated imines (iminoesters). In general, ketenes are generated from the appropriate acid chloride and a tertiary amine. The major or sole product of the cycloaddition is usually the cis‐β‐lactam, although a few exceptions showing trans selectivity are known. In this way β‐lactams with a widely varying substitution pattern at the C‐3 and C‐4 positions of the ring are constructed stereoselectively. The diastereoselection of the cycloaddition process can be controlled with variable success from chiral groups attached to either the ketene or the imine component, or alternatively to both. This method, in turn, has proved to be valuable for the synthesis of precursors of important β‐lactam antibiotics, and new successful applications can be expected in the near future.

In the last two decades, the better understanding of the mechanistic aspects of the beta-lactams' biological activity and their inhibition, and the chemical exploitation of beta-lactams as synthetic intermediates in organic chemistry, have experienced a continuous and somewhat complementary advance. A prerequisite for such a development has been the accessibility of enantiopure beta-lactams. The latter are now routinely prepared most often through the ketene-imine cycloaddition reaction, also termed the Staudinger reaction. This review accounts for the recent progress made in the asymmetric synthesis of beta-lactams (with special emphasis in the Staudinger reaction approach), as well as in their use as synthetic intermediates en route to natural products, including alpha- and beta-amino acids and peptides derived therefrom.

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ACCOUNT 1813 b-Lactams as Versatile Intermediates in aand b-Amino Acid Synthesis b-Lactams a s V e r s a t i l e I n t e r m e d i a t e s i n a-a n d b-Amino A c i d S y n t h e s i s Abstract: The use of b-lactams as synthetic intermediates has recently found considerable interest, driven by the accessibility of enantiomerically pure b-lactam building-blocks and by the discovery of selective methods for the b-lactam ring opening. N 1 -C 2 and C 2 -C 3 bond cleavage of b-lactams can now be effected cleanly by different nucleophiles, in an intra-or intermolecular fashion, under isomerization-free conditions. By this way, an array of diverse, densely functionalized, cyclic as well as open chain, aand b-amino acid derivatives, including peptides, have been synthesized. Examples from our laboratory and from others are provided.

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