Studies related to penicillins. Part 19. Alkylations of (3R)-3-{(1S,5R)-3-benzyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl}-4,4-dimethylthietan-2-one

Abstract

The title compound (7a) undergoes epimerisation at position 3 of the thietanone ring in the presence of triethylamine; the equilibrium ratio of the starting material and its epimer (9a) is ca. 1.5 : 1. Methylation of the compounds (7a) or (9a) also occurs at position 3 of the thietanone ring, in the presence of sodium hydride–methyl iodide; a ca. 1 : 1 mixture of the (3R)-3-methylthietanone (7b) and the (3S)-3-methylthietanone (9b) is produced when tetrahydrofuran is used as the solvent whereas a ca. 2.5 : 1 mixture of the compounds (7b) and (9b) is formed when NN-dimethylformamide is employed. With potassium t-butoxide-t-butyl bromoacetate in NN-dimethylformamide, the thietanone (7a) affords a ca. 6 : 1 mixture of the (3R)-3-t-butyloxycarbonylmethylthietanone (7c) and its (3S)-isomer (9c). Only the (3R)-3-allylthietanone (7d) is formed when the thietanone (7a) is treated with potassium t-butoxide–ally iodide in NN-dimethylformamide.

Attempts to hydroxymethylate the thietanone (7a), by using potassium t-butoxide–formaldehyde, were thwarted by further reactions of the hydroxymethyl derivative (7e) or (9d), resulting in the formation of a mixture of 7-(α-mercapto-α-methylethyl)-3-phenylacetamido-1-aza-5,9-dioxabicyclo[5.3.0]dec-2-ene-4,8-dione (16a) and 11,11-dimethyl-5-phenylacetamido-3,9-dioxa-12-thia-7-azatricyclo[5.3.2.0^1,7]dodecane-4,10-dione (20).