Bicyclo octanes rearrangement

The rearrangement of isopent-3-enyl epoxy esters with Cp2ZrCl2/AgC104 yields ABO esters (2,7,8-trioxabicyclo[3.2.1]octane Asymmetric Bicyclo-Octane esters), which are base-stable protecting groups for carboxylic acids [57,79,80] (Scheme 8.40). 

Base-induced rearrangement of bicyclo[2.2.2]octane oxide 67 gives predominantly bicyclo[2.2.2]octanone 68 (Scheme 5.15), which once again indicates that close proximity between the carbenoid center and the C-H bond into which it may insert is important if such an insertion is to occur [30]. In comparison, the sense of product distribution is reversed for the related substrate bicyclo[2.2.2]octadiene oxide 70 on treatment with LDA [15, 22], alcohol 72 being the favored product. 

Scheme 13.17 depicts a synthesis based on enantioselective reduction of bicyclo[2.2.2]octane-2,6-dione by Baker s yeast.21 This is an example of desym-metrization (see Part A, Topic 2.2). The unreduced carbonyl group was converted to an alkene by the Shapiro reaction. The alcohol was then reoxidized to a ketone. The enantiomerically pure intermediate was converted to the lactone by Baeyer-Villiger oxidation and an allylic rearrangement. The methyl group was introduced stereoselec-tively from the exo face of the bicyclic lactone by an enolate alkylation in Step C-l. 

The results obtained in combination with the data on the transformations of cations 9-11, led to the conclusion that 1,2-shifts of methyl groups occur readily in carbocations having a pentalene fragment. On the basis of the data obtained for rearrangements of such carbocations, an alternative mechanism has been proposed (52) for the rearrangement of structurally related carbocation 16 having a bicyclo[3.3.0]octane skeleton described in (33) (Scheme 12). 

Under Ritter reaction conditions the cycloocta-1,5-diene 392 is prone to undergo trans-annular cyclization into cA-bicyclo[3.3.0]octane derivatives (equation 141)194. Norbor-nadiene 393 and 5-ethylidenenorbomene 394 rearrange under the same conditions to... 

It has been shown" that isomerization of the exocyclic allylic system of the five-membered ring D of kaurenols depends on the orientation of the C(15) hydroxyl group. The total synthesis of methyl atis-16-en-19-oate, a tetracyclic diterpenoid possessing a bicyclo[2.2.2]octane skeleton, has been accomplished" using a homoallyl-homoallyl radical rearrangement process of methyl 12-hydroxykaur-16-en-19-oate monothioimid-azolide (280) as the pivotal step. Two plausible mechanisms have been presented" ... 

The last synthesis to evolve which is due to Ito and his coworkers is interesting in that it relies on a stereospecific skeletal rearrangement of a bicyclo[2.2.2]octane system which in turn was prepared by Diels-Alder methodology (Scheme XLVIII) Heating of a toluene solution of cyclopentene 1,2-dicarboxylic anhydride and 4-methylcyclohexa-l,4-dienyl methyl ether in the presence of a catalytic quantity of p-toluenesulfonic acid afforded 589. Demethylation was followed by reduction and cyclization to sulfide 590. Desulfurization set the stage for peracid oxidation and arrival at 591. Chromatography of this intermediate on alumina induced isomerization to keto alcohol 592. Jones oxidation afforded diketone 593 which had earlier been transformed into gymnomitrol. 

The full paper on the synthesis of onikulactone and mitsugashiwalactone (Vol. 7, p. 24) has been published.Whitesell reports two further useful sequences (cf. Vol. 7, p. 26) from accessible bicyclo[3,3,0]octanes which may lead to iridoids (123 X=H2, Y = H) may be converted into (124) via (123 X = H2, Y = C02Me), the product of ester enolate Claisen rearrangement of the derived allylic alcohol and oxidative decarboxylation/ whereas (123 X = 0, Y = H) readily leads to (125), a known derivative of antirride (126) via an alkylation-dehydration-epoxi-dation-rearrangement sequence. Aucubigenin (121 X = OH, R = H), which is stable at —20°C and readily obtained by enzymic hydrolysis of aucubin (121 X = OH, R = j8-Glu), is converted by mild acid into (127) ° with no dialdehyde detected sodium borohydride reduction of aucubigenin yields the non-naturally occurring isoeucommiol (128 X=H,OH) probably via the aldehyde (128 X = O). ... 

Table 4. Bicyclo[3.2.0]heptan-6-ones and a Bicyclo[4.2.0]octan-7-one by Base-Catalyzed 1234-1243 Rearrangement of y-Oxo />-ToluenesuIfonates...

Bicyclo[4.2.0]octan-7-ones 7, substituted at C8, resulted from addition of 7-lithio-7-methoxy-bicyclo[4.1.0]heptane to saturated and unsaturated aldehydes and subsequent rearrangement.146148... 

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... 

Solvolytic rearrangement of formic acid gave quantitatively the most stable product of the homoallyl rearrangement, e.vu-bicyclo[3.2.1]oct-2-en-7-yl formate (10). In 70% aqueous dioxane buffered with triethyl-amine at 80°C, the same tricyclic dinitrobenzoate 9 furnished a mixture of 78% tricy-clo[3.2.1.02 7]octan-3-ol (11) and 22% c.w-bicyclo[3.2.1]oct-2-en-7-ol (12).21... 

Interestingly, Lewis acid catalyzed rearrangement of 6-methyltricyclo[8.2.0.0, 6]dodecan-9-one gave the spiroannulated triquinane ketone (l/ , 5/ )-l-methylspiro[bicyclo[3.3.0]octane-2,lf-cyclopentane]-6-one as the major product (70%).85... 

In the presence of proton and/or Lewis acids and strong nucleophiles bicyclo[4.2.0]octan-7-ones were converted to 3-substituted cyclooctanones (see table overleaf). 3-Iodocyclooctanones were formed on treatment with iodotrimethylsilane and catalytic amounts of zinc(II) iodide.31 If l,8-diazabicyclo[5.4.0]undecene was added after the rearrangement a cyclooctenone33 was isolated. Similarly, benzenethiol underwent addition to the central bond of bicyclo[4.2.0]octan-6-ones in the presence of zinc(ll) chloride and hydrochloric acid under anhydrous conditions to form 3-(phenylsulfanyl)cyclooctanones.34... 

Perfluorinations of cyclooctane, -decane, -dodecane and -octadecane with cobalt(III) fluoride at 130-300°C give mainly rearranged products.47 For example, cyclooctane at 200°C gives perfluoro(bicyclo[3.3.0]octane)(2%), perfluoro bicyclo[3.3.0]oct-1(5)-ene (8 %), perfluo-ro(ethylcyclohexane) (26%), perfluoro(methylcycloheptane) (33%), and perfluorocyclooctane (31 %). A small amount of 177-pentadecafluorocyclooctane is also isolated. 

Retro-Claisen rearrangement The formyl bicyclo[2.2.2]octane 1 when heated with a catalytic amount of HO Ac at 110° rearranges to the vinyl ether 2, probably because of relief of the strain associated with the vic-quatemary carbon centers. This retro-Claisen rearrangement occurs rapidly at 0° in the presence of BF3 0(C2H5)2 (0.1 equiv.).10... 

The novel arenium ion 95 was synthesized266 by one-electron oxidation of the triphenylene-based starting compound to form a radical cation which abstracted a chlorine atom with a concomitant rearrangement to yield the hexachloroantimonate salt. The arenium ion character is apparent from the 13C spectrum (three signals at 813C 212.9, 187.6, and 173.6) and from the bond distances, which are very close to those shown for ion 91. Cation 95 can be stored at room temperature for months. This exceptional stability was attributed to the annelation to the two bicyclo[2.2.2]octane units and the spiroconjugation effect of the fluorenyl moiety.267... 

Conformational analysis explains why the relatively strained 2,6-dioxa-bicyclo[3.2.1]octane skeleton 98 of 3,6-anhydro-D-gluco- and -D-manno-pyranose tends to recyclize rapidly in the presence of methanolic hydrogen chloride into the less-strained 2,6-dioxabicyclo[3.3.0]octane skeleton 99 of the 3,6-anhydrohexofuranose. Obviously, such rearrangement cannot take place with the galacto or talo configurations, and consequently, acyclic acetals are formed.390,391... 

Suitably constructed bridged carbenes exhibit a tendency for structural rearrange ment and undergo the so-called foiled methylene reaction 141 142) with formation of bicyclo[3.3.0]octane derivatives. The behavior of P6143) and 97144) exemplifies such conversions. Carbonium ion analogies to such reactions are known. ... 

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