3-Diethoxyphosphorylpropionic Acid, a Convenient Reagent for the Synthesis of ß,γ-Unsaturated Amides

Abstract

Abstract β,γ-Unsaturated amides are versatile intermediates in the organic synthesis e.g. in the synthesis of various analogues of penicillins, cephalosporins, carbapenems, and 1) functionalized monocyclic β-lactam antibiotics. We have now developed a novel route to β,γ-unsaturated. amides 3 starting from di ethoxyphosphory l propionic acid (1). Dilithium derivative of the acid 1 reacts with a variety of carbonyl compounds to give lactons 2. Treatment of 2 with amines results in nucleophilic lacton ring opening with subsequent Horner-Emnons olefination to give 3 (R5=HI. Alkylation of the lithiated lacton 2 with alkyl halogens folloved by the ring opening-olefination sequence provides d-substituted α, -unsaturated amides 3 (R5=alkyl).