Preparation of α,β-unsaturated γ-keto aldehydes and new tetronic acid and pyridazine derivatives by oxidative transformations of alkoxyallene-based dihydrofurans

Oxidation of 3-alkoxy-substituted dihydrofuran derivatives 6 and 11 with DDQ unexpectedly provided alpha,beta-unsaturated gamma-keto aldehydes 10 and 12. A mechanism for this new oxidative ring-cleavage is presented. Since alpha,beta-unsaturated gamma-keto aldehydes are versatile intermediates, other 3-methoxy-substituted dihydrofuran derivatives 24, 26, and 28 were prepared from lithiated methoxyallene and the corresponding aldehydes. Oxidation of dihydrofuran derivatives with DDQ and subsequent treatment with sodium chlorite furnished hydroxy-substituted tetronic acid derivatives, such as 30 and 31. Condensation of 30 with hydrazine provided the unsaturated pyridazinone derivative 32. A second route to pyridazine derivatives involves DDQ-mediated oxidation of dihydrofurans and reaction of the products with hydrazine hydrate. This leads to 4-methoxypyridazines 33, 34, 35, and 36 in good overall yields. The oxidative transformations of dihydrofuran derivatives reported here demonstrate new examples of reactivity umpolung; the lithiated alkoxyallenes are equivalents of the unusual synthons B and C, which represent anions of malondialdehyde or malonaldehydic acid. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.