Bicyclo octane framework

In a recent total synthesis of the novel neurotrophic agent merrilactone A (22, Scheme 4) by Inoue and Hirama [24], key intermediate 21 with the cis-bicyclo[3.3.0] octane framework embedded within the caged pentacycle 22 was elaborated from cyclobutane 18 by a sequence of RCM and immediate cleavage of the resulting bicyclic vicinal diol 19 to raeso-diketone 20. Cyclooctenedione 20 then underwent regioselective transannular aldol reaction at low temperature (LHMDS, THF, -100 °C) to produce a 3 1 mixture of isomers in 85% combined yield. The major isomer 21 with the required stereochemistry was then converted into the racemic natural compound ( )-22 in 19 steps. 

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). 

In this chapter, we document the many transformations to which compounds having the bicyclo[3.3.0]octane framework have been subjected. Since many of these reactions can now be regarded as classical", we have not attempted to be completely exhaustive in our coverage. Rather, the interconversions discussed have been selected because they are exemplary. To our knowledge, however, the reference citations made in this and earlier sections constitute a complete listing. Any search for information on these compounds in thereby simplified to this extent. 

There are also several reports on the enantioselective hydrolysis of bicyclic secondary alcohols possessing the bicy-clo[2.2.1]heptane and bicyclo[2.2.2] octane framework. Again, with this type of substrate the lipases appear to exhibit strong preference for the endo isomers with the (/ )-configured esters preferentially hydrolyzed. 

Besides the obvious D3 twisted bicyclo[2.2.2]octane framework, another characteristic of pentacyclic [m.n.o] triblattanes is the presence of a strained bicyclo [2.2.0] hexane moiety whose facile reductive cleavage of the central single bond correlates this class of triblattanes to the corresponding tetracyclic [m.n] triblattanes. Figure 21 illustrates the configurational correlation between these two classes of triblattanes the key liaison compound is the (+) <, 0-unsaturated ketone 172, whose absolute configuration had been related to that of the levorotatory carboxylic acid (-)-151 via (+)-methyl 3-(enrfo-2-norbornyl) propionate (179) (146). 

Follow-up studies indicated one could reduce the number of equivalents of the oxazaborolidine species to make the process catalytic. With the establishment of this mechanistic foundation, it became possible to rationalize the outcome of this reaction knowing the structure of the catalyst. nB NMR confirmed the formation of a 1 1 complex between 10 and BH3-THF for R = H (11), while for the species R = Me (11) a single crystal X-ray structure was obtained.8 The cw-fused nature of this complex is a result of the concave shape of this bicyclo[3.3.0]octane framework. 

Formation of allylketones 567 from allyl -ksto esters 563 and allyl enol carbonates 566 is the Pd-catalyzed Carroll rearrangement. As a related reaction, Pd-catalyzed regioselective intramolecular allyladon of the allyl enol ether of 6-keto ester 574 occurred as shown by 575 in DMSO, and afforded a mixture of the endo- and eJco-bicyclo[3.2.1]octane frameworks 576 and 577 using DPPE as a ligand. PPh3 is not suitable [207]. 

The photochemical [2 + 2] addition of olefins to cyclohexenes remains the principal method of preparing bicyclo[4,2,0] octane frameworks. The kinetics of the addition of 3-phenylcyclohexenone to tetramethylethylene have been investigated. Direct or sensitized irradiation gives the [2 + 2] adduct. The enone state is the reactive species in either case. The additions with norbornene and cyclopentene have also been discussed. 

Kohnz H, Diill B, Mullen K (1989) From the Bicyclo[3.3.0]octane framework to multiply bridged [12] annulenes and semibullvalenes. Angew Chem Int Ed Engl 28 1343-1345... 

AAS = atomic absorption spectroscopy ATOF-MS = aerosol time-of-flight mass spectrometry 2,6-ndc = 2,6-naphthalenedicarboxylate bdc = 1,4-benzenedicar-boxylate bpdc = 1,3,5-benzenetricarboxylate bpydc = 2,2 -bipyridine-5,5 -dicarboxylate btb = 4,4, 4"-benzene-1,3,5-triylbenzoate btc = 1,3,5-benzenetricarboxylate 3D = three-dimensional dabco = l,4-diaza[2.2.2]bicyclo-octane EDX = energy-dispersive X-ray spectroscopy EXAFS = extended X-ray fine structure Fc = ferrocenyl ICP-AES = inductively coupled plasma atomic emission spectroscopy MOF = metal-organic framework PSD = postsynthetic deprotection PSM = Postsynthetic modification PXRD = Powder X-ray diffraction 1,4-ndc = 1,4-naphthalenedicarboxylate SALE = solvent-assisted linker exchange SBU = secondary building unit ... 

A variety of compounds containing a P,y-enone chromophore in a complex molecular framework have been synthesized and their photochemical reactions have been examined. In the majority of the chromophoric systems, the P,y-enone group is part of a bicyclo[2.2.2] octane framework in which the oxa-di-ji-methane reaction is most general and efficient. Mehta and Srikrishna reported an oxa-di-Jt-methane reaction in the tricychc compound 131 and its halo analogue that, upon sensitized irradiation, gave 132. It is interesting to note that [jt -l-Jt ]-cycloaddition was not observed. Similarly, the P,y-enone 133 underwent the ODPM reaction to give the compound 134 with a cyclopropane annulated bicyclo [3.3.0] octane framework, in excellent yield (Scheme 25). ... 

Before the explanation of ladder poly silanes is started, ladder compounds of other Group 14 elements are briefly mentioned. Hydrocarbons with a ladder-shaped carbon framework are known as ladderanes. The study on ladderanes goes back to 1927, when bicyclo[2.2.0]hexane ([2]ladderane) was synthesized by the reduction of dy-l,4-dibromocyclohexane with sodium.19 Ladderanes so far reported are tricyclo[4.2.0.02,5]octane ([3]ladderane),20 tetracyclo[4.4.0.02,507,1°]decane21 ([4]ladderane), and a number of their derivatives (Fig. 3). 

The cyclohexasilane ring of trans-lfl has a chair form and both chlorine atoms occupy axial positions. The cyclotetrasilane ring has a folded structure with the fold angles of 33.0 and 33.6°. The structure of the silicon framework of trans-lfl resembles that of bicyclo[4.2.0]octane, in which the cyclohexane ring has a chair form and the cyclobutane ring has a folded structure.67... 

The PK reaction allows access to complex molecular frameworks. In 2007, Mukai and co-worker reported the synthesis of three related alkaloids by using the PK reaction twice in the same molecule - initially to construct a bicyclo[4.3.0]nonane carbon framework (57 — 58) and then a second time to fuse a bicyclo[3.3.0]octane skeleton onto the initial framework (59—>60 -Scheme 22).70... 

A novel titanium containing zeolite mordenite has been synthesized hydrothermally using 1,4 diaza bicyclo 2,2,2 octane (DABCO) as a templating agent for the first time. Physicochemical characterization of the sample showed that Ti atoms are part of the framework, probably in tetrahedral co-ordination. These zeolites have been found to be active catalysts in phenol hydroxylation with hydrogen peroxide as an oxidant. 

A somewhat more complex case is rqvesented by the two, stereoisomeric bicyclo[3.3.0]octanes shown below. The AS values for each of the monosubstituted compounds (endo- or exo-2-methyl, endo- or exo-3-hydroxy, and exo-6-methyl) can be added to find a predicted total effect. These values can then be added to the shift values of the parent to arrive at a predicted absorption for each of the framework carbons. In this case the predictions are generally close to the observed spectrum so long as the substituents do not interact with each other either sterically or electronically. 

Frejd and co-workers used a ring-closing metathesis strategy as the key transformation in their synthesis of several novel spiro-cyclohexene bicyclo[2.2.2]octane derivatives. Spiro-cyclohexene bicyclo[2.2.2]octane derivatives are rare molecular frameworks, with only a few examples reported to date. Olefin metathesis of diastereomeric homoallylic alcohols 200 and 202 using 10 mol % of 3 in refluxing dichloromethane provided the corresponding spirocyclic carbocycles 201 and 203 in 84 and 85% yields, respectively. 

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