Convenient Synthesis of Penam-Type β-Lactams Utilizing Methylseleno Promoted Ketene-lmine Cycloaddition Reaction

Abstract

A convenient synthetic procedure for penam-type β-lactams utilizing methylseleno-promoted ketene-imine cycloaddition reaction has been developed. Several alkoxyketenes [11 a, d] were treated with racemic and optical active alkyl 2-methylseleno-2-thiazoline-4-carboxylates [6]∼[8] to give the C 5-methylseleno-substituted penams [12]∼[16] and [33] in a highly stereoselective manner and in good yields. Reductive demethylselenation of compounds [6]∼[8] and [33] by treating with (n-Bu)₃ SnH in refluxing THF and MeCN or in THF and MeCN at 60°C in the presence of AIBN furnished the corresponding racemic and optically active penams [17]∼[20], [22], and [34]. Some of these penam esters were successfully converted to new penamcarboxylic acids [32], [37] and the potassium salt derivatives [31], [35].