Tricyclo octane synthesis

The photoisomerization of cyclobutanones to transient car-benes has been used as part of an interesting synthesis of muscarine (Pirrung and DeAmicis). Intramolecular oxetan formation has been used as part of novel syntheses of medium-ring ethers (1) and the tricyclo-octane (2) (Carless et al. Gleiter and Kissler). Cossy et al. have employed the photoreductive cycliza-... 

Cory and Renneboog53 have devised an efficient bicycloannulation for the synthesis of tricyclo[3.2.1.02,7]octane-6-one (66) as shown in equation 63. The method involves three steps (1) the enolate undergoes an initial conjugate addition to phenyl vinyl sulfone, (2) the resulting sulfone-stabilized carbanion undergoes an intramolecular Michael addition to the enone, and (3) the resulting enolate displaces phenylsulfinyl moiety from the tricyclooctanone. The amount of HMPA (3 mol equivalents) is critical for effective cyclization of the enolate. 

Another option is the twofold Michael addition/SN-type sequence of which manifold versions have been published. Thus, Padwa s group reported on the di-astereoselective synthesis of bicydo[3.3.0]octenes [199], while in another approach by Hagiwara and coworkers various tricyclo[3.2.1.0]octane derivatives and similar bridged compounds have been constructed [200]. The group of Spitzner has also been engaged intensively in Michael/Michael/SN-type processes [201]. One such ex-... 

In cycloadditions of enones to alkenes novel strategies have been adopted for ring expansion of the cycloadducts, either by the choice of appropriate alkenes, e.g. 2-(trimethylsiloxy)buta-1,3-diene,70 vmv-2-trimethylsiloxybuten-2-oales71 or 3,3-dimethylcyclopropene,72 or by using 3-oxo-l-cyeloalkene-l-carboxylates as enones.73 Asymmetric [2 + 2] photocycloaddition of cyclopent-2-enone to a (+ )-dihydrofuran acetonide constitutes the cornerstone of the synthetic strategy in the first total synthesis of the novel antitumor metabolite ( )-echinosporin.74 The cycloaddition product 25 from treatment of 2-(2-carbomethoxyethyl)-2-cyclopentenone (24) with ethene has been used as a precursor for the preparation of tricyclo[4.2.0.01,4]octane.75... 

The Wolff rearrangement has been very successfully used in the synthesis of propellanes.40 The highly strained 3-diazo[3,2.2]propellan-2-one was photolyzed in dichloromethane at — 70 °C in the presence of dimethylamine to give A W-dimethyl tricyclo[2.2.2.0 u4]octane-2-carboxamide (5), a very highly strained interesting compound with inverted geometry at the bridgehead carbons,42 in 40% yield.41... 

There are few examples of the [3+1] two-fragment cyclization reactions and of transformations from four-membered rings to seven-membered ones. These methods are rather limited in scope, because they are only for the synthesis of particular compounds, for example, 2,8-dihalo-4-thia-tricyclo[3.2.1.03,6]octanes. 

Musso has reported the synthesis of diasterane (tricyclo-[3.1.1.I2 4]octane) 15. For this first member of the series of asteranes, the decarboxylation of 16b -> 16c was best achieved via the photolysis of the Barton ester of 16a in the presence of BuSH, as shown in Scheme 5.14 Fukumoto has accomplished asymmetric total synthesis of atisine 17, where the bridged pentacyclic intermediate 18, a precursor for atisine, was synthesized via an intramolecular double Michael reaction starting with 19, Scheme 6.15 Barton protocol was favored during the late stages of the synthesis and the presence of various functionalities was easily accommodated. 

Homoconjugate additions of secondary amines to cyclopropyl ketones catalysed by acid have been reported as well as formation of certain 5,6-dihydro-4H-l,2-oxazines with hydroxylamine hydrochloride. Demuth and Mikhail have recently demonstrated that cyclopropanes of the tricyclo[3.3.0.0 ] octan-3-one type can be selectively converted to functionalized bicyclic compounds with different kinds of electrophilic/nucleophilic reagents (equation 41) the products have extensively been exploited for natural product synthesis ". ... 

Bicycloannelation.2 The a -enolate of an a,/J-cyclohexenone reacts with this phosphonium salt to form a tricyclo[3.2.1.02 7]octane in low to moderate yield. This reaction was used in a short synthesis of the pentacyclic diterpene trachyloban-19-oic acid (4). Reaction of the lithium enolate of 2, prepared from podocarpic acid, with I provided the pentacyclic ketone 3, which was reduced by the Wolff-Kishner reaction to 4. 

Cyclization. In achieving the synthesis of the interesting tricyclo[3.2.1.0 - ]-octane system (1), Sauers et aV used as starting material the readily available... 

Bicyclo[2.2.2]octen-2-ones 25 afford tricyclo[3.3.0.0 ]octan-3-ones 26 in very good to excellent yields. Quantum yields for these conversions are in the range 0.5-1.0. The products have been used as building blocks in the synthesis of polycyclopentanoid terpenes and prostacyclin ana-logues. 2" - "... 

Gandolfi, C., Pellegata, R., Ceserani. R.. and Usardi, M.M., co-iVor-cycloalkyl-13,14-dehydroprostaglan-dins, Farmitalia Carlo Erba, German Patent Appl. DE 2539116, 1976 Chem. Abstr, 85, 77748, 1976. Braun, N.A., Klein, I., Spitzner. D.. Vogler, B., Braun, S., Borrmann, H., and Simon, A., Cascade reactions with chiral Michael acceptors. Synthesis of enantiomerically pure tricyclo[3.2.1.0 - ]- and bicyclo[3.2.1]octanes, Liebigs Ann. Org. Bioorg. Chem., 2165, 1995. 

Bisannelation. Tricyclo[3.2.1.0 ]octanes (3) can be obtained by reaction of enolates of cyclohexenones (2) with (1). The reaction is successful with substituents at C2, C3, and C5 in (2). This synthesis is comparable to one reported... 

The use of isotopically labeled proton donors affords a useful synthesis of labeled compounds. For example, abstraction of a proton from the methyl group of exo-3-acetyl-e do-tricyclo[3.2.1.0 ]octane (5) gave an enolate ion that could abstract a deuterium ion from solvent to produce the monodeuterated compound. Repeated exchange of the methyl protons led to a nearly quantitative yield of trideutero product 6 (Scheme 3.21). 

Haywood-Farmer, J. S., Pincock, R. E. (1969). Synthesis and solvolytic reactivity of 8-tricyclo[3.2.1.0]octane derivatives. Journal of the American Chemical Society, 9/(11), 3020-3028. 

Numerous new examples of cyclopentenone synthesis from acetylenehexacarbonyl-dicobalt complexes and norbornene derivatives have been disclosed there is evidence of steric control, and the bulky trimethylsilyl group can be employed as a removable direction-determining group to allow synthesis of 3- instead of 2-sub-stituted cyclopentenones. Reaction of (731) with sodamide in toluene gave the new octahydro-2,5-methanoazulene system (732 R = CONHj) successive hydrolysis, reduction, and esterification converted (732 R = CONHj) into (732 R = CHjOTs) which, on solvolysis, gave the homoprotoadamantane derivative (733 X = H, R R = CH2) in high yield.The carboxylic acid (732 R = COjH) underwent spontaneous Friedel-Crafts intramolecular acylation on conversion into its acid chloride to give (733 XX = O R R = CHj) and (733 XX = O, R = Cl, R = Me). Reaction of methyl a-bromocrotonate (mixture of E- and Z-isomers) with the enolates of cyclohex-2-enone affords a mixture of stereoisomeric tricyclo-[3,2,l,0 ]octan-6-ones (734 R —R are variously H or alkyl) in moderate yield. The reaction involves double Michael addition and subsequent substitution. 

A high-yield synthesis of the norsemibullvalene derivative (724) has been reported reaction of (724) with methanolic potassium cyanide produces anti-7-cya.no-endo-5-bromonorbornan-2-one in high yield which indicates synthetic scope for stereoselective introduction of nucleophiles at C-7 of the norboman-2-one system. A one-pot synthesis of tricyclo[3,2,l,0 ]octan-6-ones of the type (725), by a bicyclo-annulation procedure from cyclohex-2-enones, has been achieved. " ... 

Variations on the theme of [2 + 2]cycloaddition reactions as a route to cyclobutanes continue to be developed. 1,2-Diynylcyclobutanes (29) can be prepared by triplet-sensitized photochemical dimerization of the corresponding enynes in general, this method cannot be used for the efficient synthesis of more highly substituted cyclobutanes. Similar photochemical methods have also been used to prepare a range of substituted ci5-l,2-diaminocyclobutanes (30), and the tricyclic compounds (31), which can serve as precursors to the tricyclo[4.2.0.0 ]octanes (32) via the Wolff rearrangement. ... 

General Methods.—The use of tricyclo[3.3.0.0 ]octan-3-ones for the synthesis of cyclopentanoid antibiotics has been reviewed,as has Trost s work on the synthesis of cyclopentanoids. ... 

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