Sulfur-free penicillin derivatives. VII. Multiple functionalization of 2-azetidinyl-3-methyl-2-butenoates

The title compounds, substituted with chlorine in the 4′-position and with phthalimido, 2,2,2-trichloroethoxycarbonylamino, or phenoxycarbonylamino in the 3′-position of the azetidinone ring, have been converted to bis-allylic formates via bromination of both methyl groups with excess N-bromosuccinimide, and displacement of both bromines by formate ions in methylene chloride solvent. The diformates react smoothly with a deficit of a boron halide to form E/Z mixtures of halogeno-formates, in which the E-isomer predominates. Depending on the 3′-azetidinyl substituent, these halogeno-formates undergo a second displacement with acetate either with retention of olefinic geometry or inversion of olefinic geometry. The mechanisms of these reactions are discussed, along with further transformations leading to hydroxylactones, halogenolactones, halogenohydrins, and other compounds. Examination of the proton magnetic resonance spectra of twenty-one compounds reveals that methylene protons cis to the β-lactam nitrogen atom of a methyl 2-azetidinyl-2-butenoate are found at higher field than methylene protons cis to the methoxycarbonyl group. This observation appears to provide a more reliable criterion for the assignment of configuration to geometrical isomers than one based on the magnitude of the chemical shift nonequivalence of the E and Z methylene protons.