Total synthesis of analogues of the β-lactam antibiotics. Part 4. 4-t-Butoxycarbonyl-8-oxo-1,3,4-triazabicyclo[4.2.0]oct-2-ene-2-carboxylates

Abstract

t-Butyl hydroxy(4-iodomethyl-2-oxoazetidin-1-yl)acetate (6a) was transformed into t-butyl 4-t-butoxycarbonyl-8-oxo-1,3,4-triazabicyclo[4.2.0]oct-2-ene-2-carboxylate (9a) by sequential reactions involving thionyl chloride [to give the chloroacetate (7a)], t-butyl carbazate [to give the 2-t-butoxycarbonylhydrazinoacetate (5a)], and silver(I) oxide. In the last reaction, the 2-t-butoxycarbonylhydrazinoacetate (18a) is a likely intermediate. The structure of compound (9a) was supported by its conversion into methyl 1-t-butoxycarbonyl-3-methoxycarbonyl-1,4,5,6-tetrahydro-1,2,4-triazin-5-ylacetate (11b) by the action of sodium hydroxide followed by iodomethane, and confirmed by a single crystal X-ray analysis. The p-nitrobenzyl and benzyl esters of the triazabicyclo-octene, i.e. compounds (9c,d), were prepared from the carbinols (6b,c) by a similar reaction sequence. Hydrogenolysis of the benzyl ester (9d) gave the acid (9b), the sodium salt of which lacked antibacterial activity.