Improved Syntheses and Some Selective Transformations of 2,2,4,4-Tetrachloro-8-oxabicyclo[3.2.1]oct-6-en-3-ones

Abstract

The methyl- and alkenyl-substituted furans 1b-h react with pentachloroacetone (2) and sodium 2,2,2-trifluoroethoxide solution to form the title compounds 3b-h in good yield. With the furans 1i-m bearing an oxygen or a sulfur heteroatom in the side chain, moderate yields are obtained. Dechlorination of the [4+3] cycloadducts 3 with the Zn-Cu couple leads to the corresponding oxabicyclic ketones 4. On catalytic hydrogenation of the tetrachlorooxabicyclooctenones 3a-c hydrogenolysis of the exo-carbon-chlorine bonds occurs, leading to the endo-2,endo-4-dichloro-8-oxabicyclooctan-3-ones 8a-c. With lithium aluminum hydride and Grignard reagents, 8a and 3a form the endo-3-alcohols 12a-c and 13, respectively, the latter with uncertain configuration at C-3, in a highly stereoselective manner. The ether bridge in the dechlorinated oxabicyclooctenones 4b, 4f, and 4g can be cleaved by means of trimethylsilyl triflate/triethylamine to produce the tropones 5b, 5f, and 5g. Hydrogenation of 1,5-dimethyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (4c), followed by Wolff-Kishner reduction, affords 1,5-dimethyl-8-oxabicyclo[3.2.1]octane (7). m-Chloroperbenzoic acid epoxidizes the alkenyl side chain of the tetrachlorinated oxabicycles 3d, 3e, 3g, and 3h in a site-selective reaction. In contrast, from the dehalogenated oxabicyclic ketone 4g the bis(epoxide) 14 is obtained.

Hexachloroacetone as a Precursor for a Tetrachloro-substituted Oxyallyl Intermediate: [4+3] Cycloaddition to Cyclic 1,3-Dienes

“…2-Methylfuran, 2,5-dimethylfuran, 2-(but-3-enyl)-3-methylfuran, and 3-methyl-2-(3-methylbut-3-enyl)furan gave the wellknown oxabicycles 2d-g [4] in yields ranging between 40 and 50% (Table 1). In all cases, the yields of the [4+3] cycloadducts were lower than with the PCA procedure, but the preparations were not optimized.…”

“…43-45 °C (2b, ref. [4]: 47-48 °C). Both GLC and thin layer chromatogram (PE/EA 20:1) showed that the substance was still contaminated.…”

“…For sodium trifluoroethoxide/trifluoroethanol (NaTFE/TFE) reagent, see ref. [4]. Furan, 2-methylfuran and triethyl phosphite were commercially available products (Fluka, Merck).…”

“…A tetrachloro-substituted oxyallyl intermediate has been generated from pentachloroacetone (PCA) and utilized for many [4+3] cycloaddition reactions with 1,3-dienes and furans [1][2][3][4][5]. On preparation of PCA by chlorination of acetone, hexachloroacetone (HCA) is formed as a by-product in varying amounts [6].…”

Synthetic Approaches to Small Cluster Oligosaccharide Mimetics

“…An article by the Föhlisch group [119] alerted us to 8-oxabicyclo[3,2,1]oct-6-en-3-ones which contain both a pyran and a furan ring. These [3+4]-cycloaddition products appear [120] to be promissing starting materials for syntheses of C-glycosides.…”