Studies on the syntheses of heterocyclic compounds—DCCLXII : Alternative synthesis of trans-3-(1'R *-hydroxyethyl)-4-(2',2'-dimethoxyethyl)-2-azetidinone, a synthetic intermediate of thienamycin

Abstract

Synthesis of trans-3-(1'R *-hydroxyethyl)-4-(2',2'-dimethoxyethyl)-2-azetidinone ( 5), an important intermediate for the synthesis of thienamycin ( 1), was investigated starting from the isoxazoline derivatives 3 and 9. The most effective method was catalytic hydrogenation of trans-4-t-butoxycarbonyl-3-(2,2'-dimethoxyethyl)-5-methyl-isoxazoline ( 9) with Adams catalyst in acetic acid, followed by trimethylsilylation of the resulting epimeric aminoesters 11A and B, cyclization with EtMgBr, and deblocking. Novel reductions of the isoxazolines with sodium borohydride and nickel chloride or with diborane followed by catalytic hydrogenation were also reported.