Cyanophthalide annulation with 4-(5-alkoxy-2-furyl)-3-buten-2-one. Application to the synthesis of a (naphtho)pyrano-.GAMMA.-lactone.

Abstract

Reaction of lithiated 3-cyano-1(3H)-isobenzofuranone (7) with 5-substituted 2-furfuralacetones 6a-c and subsequent O-methylation of the resulting naphthohydroquinones afforded 2-acetyl-3-furylnaphthalenes 8a-c in good yields. Annulation of the dialkoxyphthalides 12a, b with 6a could also be carried out to give 13a, b. The 5-tert-butoxy-2-furyl compounds were stereoselectively transformed into (1R*, 3R*, 4R*)-pyrano-γ-lactones 16a, 18a, b in high yields by a modification of the Kraus method (LiAlH4 reduction followed by treatment of the product carbinol with p-toluenesulfonic acid (TsOH) in acetonitrile and then with 1, 8-diazabicyclo[5.4.0]undec-7-ene in toluene at low temperatures). The 5-methoxy-2-furyl compound 9b also afforded 16a stereoselectively in one step (treatment with TsOH), but this compound was less effective as a substrate of the pyrano-γ-lactone annulation since a side reaction leading to the spiro-γ-lactone 17 became significant. The 5-phenylthio compound 9c failed to give 16a under a variety of conditions.