Spiro-fused β-lactam oxadiazolines by formal [2+2] cycloaddition of 2-imino-Δ3-1,3,4-oxadiazolines to ketenes

Abstract

Sixteen spiro-fused β-lactam oxadiazolines were prepared by treatment of 2-imino-Δ3-1,3,4-oxadiazolines with carboxylic acid chlorides in the presence of triethylamine. Two others were prepared by methylation of β-lactam oxadiazoline anion equivalents with methyl iodide. Isomer ratios, spectra, stereochemistry, and relative thermodynamic stabilities of a pair of diastereomeric β-lactam oxadiazolines are reported. Three cases of failure of the approach are noted, to define some of the limitations. The oxadiazolines are known to undergo thermolysis, in solution, to afford N2, a ketone, and a β-lactam-4-ylidene. Phenyl substitution at C5 of the oxadiazoline ring serves to decrease the thermolysis temperature by about 50 °C but it also leads to the onset of a side reaction that lowers the yield of ylidene. This observation indicates a limitation of the oxadiazoline approach to the generation of β-lactam-4-ylidenes.