Synthesis of 2-Azetidinones from Serinehydroxamates: Approaches to the Synthesis of 3-Aminonocardicinic Acid

Abstract

Protected forms of 3-aminonocardicinic acid (3-ANA, 1) have been synthesized in a short and efficient manner from L-serine. The serine derived O-benzyl hydroxamate 4 was cyclized to the l-(benzyloxy)-2-azetidinone 5 with Ph3P/CCl4/Et3N. N-0 reduction gave the N-unsubstituted 2-azetidinone 6. While conventional methods proved unsatisfactory for the N-alkylations of 6, both phase-transfer-catalyzed alkylation and rhodium acetate catalyzed carbenoid insertion provided 3-ANA derivatives in good yield. Other alkylation methods and studies related to deprotection of the 3-ANA derivatives are also described. © 1981, American Chemical Society. All rights reserved.