A Novel Synthesis of 2‐Alkoxy‐3‐hydroxytropones and 2,7‐Dihydroxytropones from Dialkoxy‐8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐ones

Abstract

Trichloro‐substituted 8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐ones 6 and 7 are solvolysed by methanolic sodium methoxide to form the bicyclo[3.2.1] α,α‐dimethoxy ketones 13 and 14, with preservation of one chloro substituent. In the case of 6a, prolonged reaction time with an excess of methanolic sodium methoxide provides a trimethoxy‐substituted oxanorbornene aldehyde 19 through ring contraction. Treatment of the mixture of 13 and 14 with zinc and aqueous acetic acid affords dechlorinated α‐oxo acetals 15 and 16. Starting with the [4+3] cycloadducts derived from 2‐methylfuran and tetrachloroacetones (6b and 7b), the same procedure, but with use of ethanol or trifluoroethanol, results in the corresponding ethoxy‐ and trifluoroethoxy acetals. These compounds can be converted into the oxabicyclic compounds 15, which undergo cleavage of the ether bridge on heating with KOH in methanol, thus providing 2‐alkoxy‐3‐hydroxytropones 20, which can be dealkylated to give the 2,7‐dihydroxytropones (7‐hydroxytropolones) 29. The lithium enolate generated from the α‐oxo acetal 15a can be exo‐alkylated with methyl iodide. Michael addition with 2‐nitro‐1‐butene followed by a Nef reaction furnishes the bicyclic dioxo acetal 5. Treatment of 5 with basic methanol results in an epoxyazulenone derivative 26, and a hydroxytropone 20f, which is in equilibrium with the cyclic hemiacetal form 28. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Inhibition of the ANT(2″)-Ia resistance enzyme and rescue of aminoglycoside antibiotic activity by synthetic α-hydroxytropolones

“…Alternatively, other methods are available to target monosubstituted α-hydroxytropolones that could be used. 14 …”

New method for the synthesis of β-tropolones: Structures of condensation products of o-quinones with 2-methylquinolines and the mechanism of their formation

“…5, 6 Recently, a more convenient four step method has been developed based on the cycloaddition reaction of 2 methylfuran with symmetrical tetrachloroacetone pro ducing 2 alkoxy β tropolones in 20-37% yields. 7 2 Acyl β tropolones were synthesized in moderate yields (12-66%) by the reactions of in situ generated triphenyl bismuthonium ylides with o quinones. 8 The reaction of tetrachloro o benzoquinone with acetone also produces β tropolone derivatives.…”

Synthetic Approaches to Hydroazulenes and Guaianes through [4 + 3] Cycloadditions of Oxyallyl Intermediates

“…Finally, the reactions resemble the cleavage of oxabicyclic oxo acetals to form β-tropolones. [36] Although the formation of an azulenol by cleavage of 3 was striking and interesting as a novel approach to these isomers of naphthalenols, and might open the door for attachment of an appendix at the "ortho" position (C-5) of 11, we preferred to execute the aldol cyclization with the saturated diketone (14). It was anticipated [37,38] that heterogenous catalytic hydrogenation of 2 should proceed stereospecifically from the easily accessible α-face of the bicycle, thus establishing a β configuration of the methyl group at C-7.…”