A Novel Approach to Cephalosporins From Allenylazetidinones: A New Cyclization Strategy via Tandem Cuprate Addition-Sulfenylation

Article abstract of DOI:10.1021/jo00096a045

An efficient approach to the synthesis of 3-substituted cephems bearing carbon-based substituents of choice at the C(3) position from inexpensive penicillins is described.The strategy involves the synthesis of an allenylazetidinone from penicillin sulfoxide followed by the addition of an organocuprate at low temperature.Organocuprates undergo 1,4-conjugate addition at the central allenic carbon of the allenylazetidinone to form a carbon-carbon bond which is followed by ring closure via an intramolecular sulfenylation reaction.The chemistry has been applied to the synthesis of a variety of 3-substituted cephems bearing substituents such as alkyl, cycloalkyl, aryl, alkenyl, and allyl.Precursors to the synthesis of important antibiotics, i.e.Cefadroxil, Cefixime, and Cefzil, are also available from this novel approach.The methodology is not limited to carbon-based 3-substituted cephems, but provides access to some 3-norcephalosporins as well.