Asymmetric synthesis of (3S)-2,3,4,5-tetrahydropyridazine-3-carboxylic acid and its methyl ester

Methyl (2E,4E)-5-(2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranosyloxy)penta-2,4-dienoate 16a, assembled by a Wittig condensation of tributyl(methoxycarbonylmethylene)phosphorane 19a and (2E)-3-(2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranosyloxy)propenal 20, displays excellent Re-face reactivity towards diethyl azodicarboxylate 15a, bis(2,2,2-trichloroethyl) azodicarboxylate 15b, dibenzyl azodicarboxylate 15c, diisopropyl azodicarboxylate 15d and di-tert-butyl azodicarboxylate 15e in thermal hetero-Diels-Alder reactions to give the cycloadducts 17a-e. When subjected to the action of hydrogen over palladium-carbon, the cycloadducts 17a, 17b, 17d and 17e undergo hydrogenation of their olefinic bonds to give the dihydro derivatives 18a, 18b, 18d and 18e; in the case of the cycloadduct 17c, hydrogenolysis of the benzyloxycarbonyl group also occurs to give methyl (3S)-2,3,4,5-tetrahydropyridazine-3-carboxylate 1b with an ee of 98% and 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranose 22. Compound 1b, with an ee of 98%, is also available from the dihydro derivative 18e by the action of trifluoroacetic acid; however, under the acidic conditions, a condensation reaction between the aglycone 1b and the glycone 22 competes to give methyl (3S)-2,3,4,5-tetrahydro-2-(2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranosyl)pyridazine-3-carboxylate 25. Sodium (3S)-2,3,4,5-tetrahydropyridazine-3-carboxylate 1c, with an ee of 99%, is available from the ester 1b by a saponification reaction. The trifluoroacetic acid salt 27, with an ee of 95%, is obtained from benzyl (3S,6S)-1,2-bis(tert-butoxycarbonyl)-1,2,3,6-tetrahydro-6-(2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranosyloxy)pyridazine-3-carboxylate 17g by a hydrogenation-trifluoroacetolysis sequence. A hetero-Diels-Alder reaction involving the benzyl pentadienoate 16c and di-tert-butyl azodicarboxylate 15e provides the cycloadduct 17g.