Oxabicyclo compounds

Reaction of the oxa-bicyclo system was shown to follow the same trend. Thus, migration of the methylene group was preferred in a 2 1 ratio for the exo-methylamine oxabicyclo compound 64, while the endo-methylamine provided a 12 1 mixture of 65 and 66. ... 

At>-7-Oxabicyclo[2.2.l]hept-5-ene-2-carboxylic acid - (84) was isolated as a minor component from the mother liquor of 29. Compound 84 is an epimer of 29 at C-2, and three known carba-sugar pentaacetates have been prepared from 84 as follows. 

Furans and some of its derivatives have been cyclopropanated with the ketocarbenoids derived from ethyl diazoacetate and copper catalysts. The 2-oxabicyclo[3.1.0]hex-3-enes thus formed are easily ring-opened to 1,4-diacylbutadienes thermally, thermo-catalytically or by proton catalysis 14,136). The method has been put to good use by Rh2(OAc)4-catalyzed cyclopropanation of furan with diazoketones 275 to bicyclic products 276. Even at room temperature, they undergo electrocyclic ring-opening and cis, trans-dienes 277a are obtained with fair selectivity 257,258). These compounds served as starting materials in the total syntheses 257 259) of some HETE s (mono-... 

Heterocycles Both non-aromatic unsaturated heterocycles and heteroaromatic compounds are able to play the role of ethene dipolarophiles in reactions with nitrile oxides. 1,3-Dipolar cycloadditions of various unsaturated oxygen heterocycles are well documented. Thus, 2-furonitrile oxide and its 5-substituted derivatives give isoxazoline adducts, for example, 90, with 2,3- and 2,5-dihydro-furan, 2,3-dihydropyran, l,3-dioxep-5-ene, its 2-methyl- and 2-phenyl-substituted derivatives, 5,6-bis(methoxycarbonyl)-7-oxabicyclo[2.2.1]hept-2-ene, and 1,4-epoxy-l,4-dihydronaphthalene. Regio- and endo-exo stereoselectivities have also been determined (259). 

Few structures have been solved for this kind of compound. A crystal structure of (2-R,5R,2 R,5 R)-bi(2,2 - / -butyl-1,1 -aza-3,3 -oxabicyclo[3.3.0] octan-4,4 -one prepared from the diastereoselective dimerization of the pivaloyl oxa-zolidin-5-one derivative of proline has been obtained for the determination of the absolute stereochemistry of the C-a atoms of compound 265. 

This latter compound, 36, and the isomeric 9-oxabicyclo[4.2.1]nonane, 37, were obtained as the sole products, in ca 13 87 ratio, by reaction of 3 with A-chlorosuccinimide (NCS) in protic solvents (methanol, dioxane-water mixtures)72. It is noteworthy that similar ratios of the two disubstituted bicyclononane derivatives were obtained, independently of the solvent, also by using A-bromosuccinimide (NBS) as electrophile, whereas a strongly solvent-dependent ratio was observed when A-iodosuccinimide (NIS) was used. Since these reactions should proceed through hydroxy- or alkoxyhalogenation of one of the double bonds, followed by transannular attack of the oxygen function on the cationic center which is formed on the other side of the ring by the reaction of another electrophile with the second double bond, the isomer ratio has been rationalized in terms of a different nature of the intermediates. 

A structure proposed for the lycopodium alkaloid, annotinine, was a derivative of 7-azabicyclo[2.2.1]heptane, but this is incorrect, and no naturally occurring compound is known to contain this ring system. On the other hand, the 7-oxabicyclo[2.2.1]heptane ring system is present... 

Oxabicyclo[2.2.1]hepta-2,5-dienes are usually obtainable in good yield by addition of acetylenic dienophiles to furans, although 1 2 adducts, e.g., 24, result in some cases since furans also add readily to derivatives of maleic acid. The parent compounds, 7-aza- and 7-oxa-bicyclo[2.2.1]hepta-2,5-diene, are still unknown. 

The annulation reaction of bis(trimethylsilyloxy)enol ether 26 with 1,4-pentanedione in the presence of a catalytic quantity of tiimethylsilyltriflate at -50 "C in dry dichloromethane furnishes oxabicyclo[3,2.1]heptanone 27 in 92% yield. Compound 27 is used as starting material for (+)-davanone, a major component of the South Indian plant Artemisia pattens <99T617>. 

The 3,6-hexanooxepin rat-10-oxabicyclo[fi.T2]trideca-1 (11),8,12-triene-12-mcthanol (R = ch2oh) containing a helical axis was resolved via the diastereomeric esters with (15,4/ )-camphanic acid (see p 404). X-ray analysis of one of the esters demonstrated this compound to have the P configuration as indicated (see also p 447)83. 

In another process, 13-oxabicyclo[10.4.0]hexadec-l(12)-ene is reacted with isopropyl nitrite to give 12-oxo-15-pentadecanolide, which is hydrogenated to the corresponding hydroxy compound. The hydroxy group is derivatized and the reaction product py roly zed to the unsaturated lactone. Hydrogenation of the latter yields 15-pentadecanolide [204]. 

A clever application of this reaction has recently been carried out to achieve a high yield synthesis of arene oxides and other dihydroaromatic, as well as aromatic, compounds. Fused-ring /3-lactones, such as 1-substituted 5-bromo-7-oxabicyclo[4.2.0]oct-2-en-8-ones (32) can be readily prepared by bromolactonization of 1,4-dihydrobenzoic acids (obtainable by Birch reduction of benzoic acids) (75JOC2843). After suitable transformation of substituents, mild heating of the lactone results in decarboxylation and formation of aromatic derivatives which would often be difficult to make otherwise. An example is the synthesis of the arene oxide (33) shown (78JA352, 78JA353). 

Nearly all examples of epoxidation of alkylidenecyclobutanes involve 3-chloroperoxybenzoic acid.15 58-70 This is because the conditions are mild, the workup is easy and few byproducts are formed. Generally, dichloromethane or chloroform is used as solvent. Solid sodium hydrogen carbonate is occasionally added to avoid acid-catalyzed rearrangement of the spiro compound. For example, 6-isopropylidene-l,4,4-trimethylbicyclo[3.2.0]heptan-3-one reacted with 3-chloroperoxybenzoic acid and sodium hydrogen carbonate to give 2,2,3, 3, 6-pentamethyl-spiro[3-oxabicyclo[4.2.0]octane-8,2 -oxirane]-4-one (4) in quantitative yield. However, without the use of sodium hydrogen carbonate, substantial amounts of 2,2,6,9,9-pentamethyl-3-oxa-bicyclo[4.3.0]nonane-4,8-dione (5) and 2,2,6,8,8-pentamethyl-3-oxabicyclo[4.3.0]nonane-4,9-dione (6) were also formed.15-64... 

Oxabicyclo[3.2.0]hepta-l,4,6-triene (289), a planar Sn-electron analog of 4, has been prepared by flow pyrolysis of 288 (both cis and trans) in approximately 10% yield (>95% purity) 289 is an extremely sensitive compound, polymerizing instantaneously on exposure to oxygen. In solution, where it is stable for several days, it slowly dimerizes to give the known compound 291 the pentacyclic intermediate 290 is possibly involved. In Diels-Alder reactions, 289 behaves like an olefin with cyclopentadiene it reacts immediately to give 292. Hydrogenation occurs at the same site. ... 

Antipyrine (18) a lipophilic compound that has been shown to have a high uptake by the brain is also fluorinated and consequently dehydrofluorinated.75 The cxv-addition mode is exploited for the preparation of the adducts 19 and 20 of 7-oxabicyclo[2.2.1]hept-5-ene and 2-azabicyclo[2.2.1]hept-5-en-3-ones with fluorine which arc used in the preparation of di-fluorodeoxyhexofuranosides and fluoronucleosides.76 Fluorine also undergoes addition to oxazolones 21 for the eventual synthesis of /i-fluorinated a-amino acids.77... 

Likewise, unprotected polyhydroxy compounds can be successfully fluorinated to give the products resulting from substitution of the hydroxy groups by fluorine, wn-o-lnositol reacts with sulfur tetrafluoride and anhydrous hydrogen fluoride at ambient temperature to give a moderate yield of the cyclic sulfite ester of tw/o. cfo-5,6-difluoro-7-oxabicyclo[2.2.1 heptane-e.w,e.vo-2,3-diol (6) and, alter hydrolysis, the free difluoro diol 7.61... 

A synthesis of the well-known natural products, the inositols, begins with a Diels-Alder reaction between furan and vinylene carbonate (73JOC117). Both the exo and endo oxabicyclo[2.2.1]hept-5-ene-2,3-diol carbonate adducts were obtained. fraus-Hydroxyla-tion of the endo adduct via the epoxide (33) afforded D-l,4-anhydroinositol (34). Hydrolysis of this compound with acetic acid and a small amount of sulfuric acid yielded alio- (35) and myo-inositol (36 Scheme 7). 

A new stereoselective synthesis of 1,2,3-trisubstituted cyclopentanes based on the Wag-ner-Meerwein rearrangement of a 7-oxabicyclo[2.2.1]heptyl 2-cation starts with the Diels-Alder product of maleic anhydride and a furan (78TL2165, 79TL1691). The cycloadduct was hydrogenated and subjected to methanolysis. The half acid ester (47) was then electrolyzed at 0 °C to generate a cationic intermediate via the abnormal Kolbe reaction (Hofer-Moest reaction). Work-up under the usual conditions provided the 2-oxabicyclo[2.2.1]heptane (48) in 83% yield. Treatment of this compound in turn with perchloric acid effected hydrolysis of the ketal with formation of the trisubstituted cyclopentane (49) in nearly quantitative yield (Scheme 11). Cyclopentanes available from this route constitute useful... 

Treatment of K[Pt(0,O-MeCOCHCOMe)(C-MeCOCHCOMe)X] with mineral acids affords a material, formulated as Pt(0, -MeCOCHCOMe)Cl(MeCOCH2COMe) in which neutral, enolic acetylacetone is rc-bonded to platinum via the C=C bond. On standing, solutions of this material in chloroform yield red [Pt( -Cl)(MeCOCHCOMe)] . Similar acidification of K[Pt(MeCOCHC-OMe)3] with HX (X = Cl, Br) yields Pt(l,3,5,7-tetramethyl-2,6,9-oxabicyclo[3.3.1]nona-3,7-diene)2X2,248 whereas sulfuric, phosphoric or nitric acid leads to polymeric [Pt(MeCOCHCOMe)2]. This compound, which is isomeric with the familiar Pt(0,O-MeC0CHCOMe)2, may aggregate by means of tridentate C,0,0-MeCOCHCOMe bridging ligands.244... 

Methylenesilacyclobutane 61 reacts with aldehydes thermally to give the cyclic siloxy adduct 62105. In the presence of BI Y)Lb. treatment of 61 with 1,4-dicarbonyl compounds yields the corresponding 8-oxabicyclo[3.2.1]octane skeleton 63 (equation 43)106. 

Decaisopropyl-7-oxabicyclo[2.2.1]heptasilane exhibits unique spectral properties. In the UV absorption spectrum two bands between 270-340 nm with a fairly large extinction coefficient of 5100 appear. The compound also shows considerably stronger fluorescence, with a maximum at 373 nm and a quantum yield of C> = 0.014, than the second oxidation... 

Rhodium- and copper-catalysed cyclopropanation of 8-oxabicyclo[3.2.1]octane by diazocarbonyl compounds was achieved in poor to moderate yields. Ring opening of the cyclopropane (40) upon treatment with Sml2 offered a desymmetrization of the original bicycle. 

Horse liver alcohol dehydrogenase (HLADH) catalyzes the oxidoreduction of a variety of compounds [56,57], It has been demonstrated that HLADH catalyzes the stereospecihc oxidation of only one of the enantiotopic hydroxyl groups of acyclic and monocyclic meso-diols [58,59], The authors demonstrated the oxidation of meso exo- and endo-7-oxabicyclo [2.2. l]heptane-2,3-dimethanol to the corresponding enantiomerically pure y-lactones by HLADH. NAD+ and flavin adenine dinucleotide (FAD) at concentrations of 1 and 20 mmol, respectively,... 

Some other natural compounds have been transformed for their use in the synthesis of polymers via olefin metathesis processes. As mentioned in the introduction, furans, which are obtained from carbohydrates, are perfect precursors of monomers for ROMP via simple Diels-Alder cycloadditions (n) (Scheme 25) [26]. In this regard, the first example of the ROMP of 7-oxabicyclo[2.2.1]hept-5-ene derivatives was reported by Novak and Grubbs in 1988 using ruthenium- and osmium-based catalysts [186]. The number of examples of ROMP with monomers with this generic structure is vast, and it is out of the scope of this chapter to cover all of them. However, it is worth mentioning here the great potential of a renewable platform chemical like furan (and derived compounds), which gives access to such a variety of monomers. 

The resulting 5-methylene-2-oxa-l-silacyclohexanes are insufficiently Lewis acidic to react with a second equivalent of the carbonyl compound. However, the incipient allylsilane does react with dimethyl acetals in decent yields in the presence of external Lewis acids including BF3-Et20 or AICI3. Based on these results, double allylation of dicarbonyl compounds with 3-methylene-l,l-diphenyl-l-silacyclobutane was examined, leading to the formation of 3-methylene-oxabicyclo[3.2.1]octanes. This transformation proceeded in one pot and in the presence of BF3-Et20 (Scheme 42). 

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