Bicyclo octane, preparation

C. W. Tullock, U.S.P. 3 714 273/1973 (Chem. Abs., 1973, 78, 110 713c). These products, and l,4-bis(trifluoromethyl)bicyclo[2,2,2]octane prepared similarly, are claimed to be good working fluids for an air-cooled turbine operating in a closed Rankine cycle. 

Bkycloheptane and Bicyclo-octane Derivatives.—Room temperature addition of diphenyldiazomethane to 7-t-butoxynorbornadiene yielded all of the possible 1,3-dipolar cycloaddition products (exo rule not obeyed). Pyrolysis of these adducts effects entry to the 3,3-diphenyltricyclo[3,2,l,0 ]octane system e.g. (852) is thus obtained. Procedures for the preparation of tricyclo[3,2,l,0 ]oct-6-ene-3-carboxylic acids, e.g. (853), essentially isomer-free have been described. Reductive dechlorination of (854), the Diels-Alder product of addition of 3,3-dimethylcyclo-propene to tetrachlorocyclopentadienone dimethyl acetal, followed by acetal hydrolysis and cheletropic loss of CO has been used to prepare 7,7-dimethylcyclohepta-triene. °... 

The intra-intermolecular polymerization of c/5-l,3-divinylcyclopentane and cyclohexane has been effected by a Ziegler catalyst prepared from titanium tetrachloride and triisobutylaluminum (38). A 38 % conversion to the bicyclo-octane polymer was obtained in 72 hours (11-42). Under similar conditions,... 

This two step procedure appears to be by far the most convenient one for preparing exo-ch-bicyclo[3 3 0]octane-2-car-boxylic acid from the readily available starting materials The first step of the procedure is also illustrative of the method of obtaining 2-substituted bicyclo[3 3 Ojoctanes4,6 from cis cn-1,5-cyclooctadiene. 

Finally, by a diastereoselective intramolecular double Michael reaction of a lithium dieno-late to an a,j6-unsaturated ester moiety, a spiro-fused bicyclo[2.2.2]octane may be prepared. These MIMIRC form the key step in the synthesis of ( )-atisine361 and (-t-)-alisirene362-365. 

A bicyclo[3.3.0]octane ring system 164 can be conveniently prepared by refluxing an acetonitrile solution of the azo compound 163 in the presence of excess of phenyl vinyl... 

Twofold Michael additions have been utilized by the groups of Spitzner [2] and Hagiwara [3] to construct substituted bicyclo[2.2.2]octane frameworks. In Hagiwara s approach towards valeriananoid A (2-6) [4], treatment of trimethylsily-enol ether 2-2, prepared from the corresponding oxophorone 2-1, and methyl acrylate (2-3) with diethylaluminum chloride at room temperature (r.t.) afforded the bicyclic compound 2-4 (Scheme 2.2). Its subsequent acetalization allowed the selective protection of the less-hindered ketone moiety to provide 2-5, which could be further transformed into valeriananoid A (2-6). 

Likewise, a number of terthiophenes have been prepared and studied. For example, radical cations of the system 69 end-capped by bicyclo[2.2.2]octane units have been found to form centrally attracted bent 7t-dimers <06JA14470>. The trimer 70 has been included in a... 

Ley SV, Baxendale IR (2002b) New tools and concepts for modern organic synthesis. Nat Rev Drug Disc 1 573-586 Ley S V, Massi A (2000) J Comb Chem Polymer supported reagents in synthesis preparation of bicyclo[2.2.2]octane derivatives via tandem michael addition reactions and subsequent combinatorial decoration. 2 104—107 Ley SV, Schucht O, Thomas AW, Murray PJ (1999) Synthesis of the alkaloids ( )-oxomaritidine and ( )-epimaritidine using an orchestrated multi-step sequence of polymer supported reagents. J Chem Soc Perkin Trans 1 1251— 1252... 

The present procedure is simpler than others previously described and gives equally good yields. It is easily adapted to the preparation of large quantities of either the diester or the diketone. It can be extended to the preparation of various alkylated 1,4-cyclohexanediones and bicyclic diketbdicarboxylic esters such as diethyl bicyclo[2.2.2]octane-2,5-dione-l,4-dicar-boxylate. 1,4-Cyclohexanedione is a useful intermediate for... 

Tetranitro-2,4,6,8-tetraazabicyclo[3.3.0]octane (bicyclo-HMX) (69) has seen considerable research efforts focused into its preparation. " Interest in bicyclo-HMX arises from its increased rigidity compared to HMX, a property which should result in higher density and... 

The preparation of bicyclo[3.3.0]octane-2,6-dione has been accomplished by intermolecular reactionsintramolecular reactions,and degradation... 

Studies by the submitters have indicated that the procedure reported here is the preferred method for the preparation of bicyclo[3.2.1]octan-3-one. It employs readily available, inexpensive reagents, and the overall yield is good. In addition, the method can be used for the synthesis of the difficultly accessible next higher homologues of bicyclo[2.2.2]oct-2-ene as well as for derivatives of norbornene. Bicyclo[3.2.2]nonan-3-one and l-methylbicyclo[3.2.1]octan-3-one have been prepared by a similar route6 in 60% and 47% yields, respectively (based on adduct). However, the preferred procedure for the formation of the dichlorocarbene adduct of bicyclo[2.2.2]oct-2-ene is that of Seyferth using phenyltrichloromethylmercury. Even in this case the overall yield is moderate (37%). 

The bicyclo[2.2.2]octane-l,4-diyl dication, 61, and its tricyclopropane derivative, 62, could not be prepared under stable ion conditions even though they were attempted under various reaction conditions. The possible existence of these carbodications was supported by Modified Neglect of Differential Overlap (MNDO) calculations. 

The Cj - and 54-symmetric tetraesters of tricyclo[3.3.0.0 ]octane (430 and 431) have been prepared by oxidation of diene 429 To access the parent hydrocarbon (435), acid chloride 432 was transformed to the derived ketene which undergoes intramolecular [2+2] cycloaddition The resulting cyclobutanone (433) serves as precursor to perester 434 whose thermal decomposition proceeds with chain transfer in competition with cleavage The unique arrangement of the carbon atoms in 435 is such that the smallest rings are all five-membered. The highly symmetric structure may be viewed as a constrained cisoid bicyclo[3.3.0]octane (as well as the symbol of NATO). 

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. 

PREPARATION OF l,3-DIMETHYL-5-OXOBrCYCLO[2.2.2]OCTANE-2-CARBOXYLIC ACID (Bicyclo[2.2.2Joctane-2-carboxyIic acid, 1,3-Oimethyl-5-oxo-)... 

Bicycloi3.3.0 octane-3,l-dione derivatives. The condensation of this reagent with 1,2-dicarbonyl compounds in an alkaline medium to give this ring system was reported some time ago1 and has since been explored in detail, mainly by Cook and Weiss.2 Detailed directions are now available for preparation of bicyclo[3.3.0]octane-3, 7-dione from glyoxal and that of the 1,5-dimethyl derivative from biacetyl (equation I).3 The condensation is applicable to a variety of diketones and yields are generally > 60%. It has been used for preparation of several natural products such as isocomene (2).4... 

Interestingly, zirconacyclopentane 246 formed by the reaction of 1,6-heptadiene with the Zr complex has the firms ring junction mainly [108]. It should be noted that the preparation of the trans ring junction in the bicyclo[3.3.0]octane system by other means is difficult. Carbonylation of 246 affords trans-fuzed bicyclo[3.3.0]octanone 247 [109,111]. The diacetoxy compound 248 is obtained by oxidative cleavage of 246. Protonation affords the frans-dimethylcyclopentane skeleton. Similar reactions occur with 1,6-enynes, and Pauson Khand-type cyclopentenone synthesis is possible by carbonylation. 

In the preparative application of [2 + 2]-photocycloadditions of cyclic enones to (substituted) alkenes, two factors concerning product formation are of decisive relevance, namely the regioselectivity and the (overall) rate of conversion. Regarding the regioselectivity in the addition to mono- and 1,1-disubstituted alkenes, Corey had shown that the preferred addition mode of cyclohex-2-enone to isobutene or 1,1-dimethoxyethylene was the one leading to—both cis- and trans-fused—bicyclo[4.2.0]octan-2-ones with the substituents on C(7) [8]. In contrast, in the reaction with acrylonitrile, the alternate orientation was observed to occur preferentially. Similar results were also reported by Cantrell for the photocycloaddition of 3-methyl-cyclohex-2-enone to differently substituted alkenes [14]. No significant differences in the overall rates of product formation for the different alkenes were observed in these studies. In order to explain these observed... 

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