Stereoselective Synthesis of 3-Substituted 4-(Formyloxy)-2-azetidinones by the Unusual Baeyer-Villiger Reaction of β-Lactam Aldehydes. Scope and Synthetic Applications

摘要

The Baeyer-Villiger oxidation of 4-formyl-β-lactams 1 with m-CPBA gave 4-(formyloxy) β-lactams 2 in a simple, efficient, and totally Stereoselective process. This reaction is one of the scarce examples of the preferred migration of a carbon moiety in an aliphatic aldehyde. The influence of the substituents at N1 and C3 of the four-membered ring in the Baeyer-Villiger rearrangement has been studied. Thus, alkyl, alkenyl, aryl, and alkyloxy 3-substituted-l-(p-anisyl)-2-azetidinones 1 form exclusively 4-(formyloxy) β-lactams 2. Amide or acetoxy substituents at C3 of the four-membered ring produce mixtures of 4-(formyloxy) β-lactams 2 and 4-carboxy β-lactams 5. The exclusive formation of carboxy derivatives is observed sometimes for 1-alkyl-substituted-2-azetidinones 1. 4-(Formyloxy) β-lactams 2 are suitable starting materials to prepare different 4-unsubstituted β-lactams 9 using β-hydroxy amides 8 as isolable intermediates. The overall transformation 4-formyl-2-azetidinone to 4-unsubstituted β-lactam is an easy and convenient Stereoselective route to these interesting types of compounds.