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Asymmetric Synthesis of β‐Lactams by Staudinger Ketene‐Imine Cycloaddition Reaction
Author(s) -
Palomo Claudio,
Aizpurua Jesus M.,
Ganboa Iñaki,
Oiarbide Mikel
Publication year - 1999
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/(sici)1099-0690(199912)1999:12<3223::aid-ejoc3223>3.0.co;2-1
Subject(s) - cycloaddition , ketene , chemistry , imine , staudinger reaction , combinatorial chemistry , lactam , alkyl , amine gas treating , stereochemistry , medicinal chemistry , selectivity , organic chemistry , catalysis
[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.