1,3-Dipolar addition reactions of 6-ethylideneolivanic acid derivatives with diazomethane and acetonitrile oxide

Abstract

p-Nitrobenzyl (5R)-3-[(E)-2-acetamidovinylthio]-6-[(Z)-ethylidene]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (1) undergoes a 1,3-dipolar addition reaction with diazomethane to afford p-nitrobenzyl(4′S,5R,6S)-3-[(E)-2-acetamidovinylthio]-4′-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-6-spiro-5′-(4′,5′-dihydro-3′H-pyrazole)-2-carboxylate (14) and the (4′R,5R,6R)-isomer (12). The analogous 6-(E)-ethylideneolivanic acid derivative similarly gives the corresponding (4′R,5R,6S)- and (4′S,5R,6R)-spirodihydropyrazoles. ¹H N.m.r. chemical-shift correlations have been used to verify that the major diastereoisomer in each case arises from α-face addition of the dipole. Related spirodihydropyrazole-carbapenems with a 3-ethylthio substituent are similarly prepared. Thermolytic elimination of nitrogen results in the corresponding 6-isopropylidene carbapenem derivatives. Hydrogenolysis of (12) and (14) gives the respective sodium salts, whilst modification of the C-3 substituent affords 3-aminoethylthio and 3-N,N-dimethylamidinomethylthio spirodihydropyrazole-carbapenems.

The (Z)-ethylidene (1) also undergoes cycloaddition with acetonitrile oxide to furnish p-nitrobenzyl (5R,5′S,6S)-3-[(E)-2-acetamidovinylthio]-3′,5′-dimethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-6-spiro-4′-(4′,5′-dihydroisoxazole)-2-carboxylate (33), as the major product. Addition in the opposite regio-sense gives the (4′S,5R,6S)- and (4′R,5R,6R)-isomers of p-nitrobenzyl 3-[(E)-2-acetamidovinylthio]-3′,4′-dimethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-6-spiro-5′-(4′,5′-dihydroisoxazole)-2-carboxylate (37) and (35), respectively. The sodium salts derived from (33) and (35) are also described.