Asymmetric synthesis of beta-lactams by Staudinger ketene-imine cycloaddition reaction

[2 + 2] Cycloaddition reactions between ketenes, bearing amino-, oxy-, or h alo- groups, and imines are recognized as being amongst the most important and direct routes to beta-lactams. Alkyl-substituted ketenes also furnished the corresponding beta-lactams upon reaction with activated imines (iminoe sters). In general, ketenes are generated from the appropriate acid chlorid e and a tertiary amine. The major or sole product of the cycloaddition is u sually the cis-beta-lactam, although a few exceptions showing trans selecti vity are known. In this way beta-lactams with a widely varying substitution pattern at the C-3 and C-4 positions of the ring are constructed stereosel ectively. The diastereoselection of the cycloaddition process can be contro lled 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 beta-la ctam antibiotics, and new successful applications can be expected in the ne ar future.