Bicyclo octane derivs

Bicycloheptane and Bicyclo-octane Derivatives.—Relative positional reactivities in nitration of benzonorbornene, benzonorbornadiene, (727), and the endo-isomer of (727) have been determined for the ipso-, a-, and /S-positions. The lower a-reactivity of (727) as compared to its endo-isomer is explained by the buttressed fused ortho effect , arising in (727) because steric hindrance between bridge and cyclopropane methylene hydrogens is sufficient to cause bridge bending, thus moving the sy -H... 

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. °... 

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... 

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... 

Me. A third possibility would be that the a-chloroenolate intermediate, which is a carbenoid, would a-eliminate a chloride ion to yield carbene 229, which would subsequently intramolecularly cycloadd onto the double bond of the enone moiety. When = H, Me as in 231 a, b, reductive cleavage of the C - bond (e.g. with lithium in liquid NH3) can produce bicyclo[2.2.2]octane derivatives 230. The... 

Despite the Tbt stabilization, the silabenzene and germabenzene are highly reactive towards water or alcohols (the RO residue adds to the heteroatom, and a hydrogen adds to a 2- or 4-carbon atom, destroying the aromaticity) benzophenone, styrene, and phenylacetylene afford bicyclo[2.2.2]octane-derivatives. In all these products, the heteroatom (Y = Si or Ge) has. sp3-hybridization. 

Diethyl malonate or ethyl cyanoacetate 187 afforded bicyclo[3.3.0]octane derivatives 188 in a tandem radical addition/transannular 5-exo cyclization sequence with cyclooctadiene 131 in 76 and 78% yield, respectively [275]. (4-Pentenyl)arenes were employed in a similar tandem radical addition/radical... 

Ley SV, Mynett DM, Koot WJ, Solid phase synthesis of bicyclo[2,2,2]octane derivatives via tandem Michael addition reactions and subsequent reductive amination, Synlett., 1017-1020, 1995. 

Aza-bicyclo[2.2.2]octane derivatives prepared by Gong (1) were effective as CCR3 receptor antagonists and used as a means of combating eosinophil-induced diseases including asthma. 

As part of a study of ring construction through transposition of activated cyclo-propanes, Danishefsky s group has scrutinized the feasibility of intramolecular homoconjugate nucleophilic additon.64 Two of the substrates examined were 34 and 35 and these were found to undergo rather efficient closure to bicyclo[3.3.0]octane derivatives when treated with strong base. The somewhat elevated temperatures allow both the cyclopropane fission and subsequent Dieckmann condensation to proceed at respectable rates. 

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. ... 

Examples are known of photoextrusion reactions which occur with ring contraction and provide bicyclo[3.3.0]octane derivatives. 1,2-Quinone diazides (e. g., 225)189 190) and bicyclo[3.3.1]nonan-9-ones (e. g., 126)191,192) are particularly... 

Oxidative fission of carbon-carbon bonds has played a pivotal role in the preparation of functionalized bicyclo[3.3.0]octane derivatives. More specifically, aqueous permanganate has been used extensively to prepare both di-207-209 and tetracarbo-xylic acids.173, 210) As shown in the case of 136 and 137, the advantage of the method resides in the ability to build stereochemistry into the precursor molecule. 

Morpholinocyclopentene has been used to elaborate bicyclo[3.3.0]octane derivatives through cycloaddition to cyanoallene220- and the reagent produced from 2,4-dibromo-3-pentanone and diiron ennacarbonyl.221 ... 

Although various bicyclo[3.3.0]octane derivatives have been known for several decades, the chemistry of this ring system and the higher polyquinanes has developed... 

Three new chirality centers are formed with high enantio- and complete diastereoselectivity in the course of the reaction of the enol triflate 37 to the bicyclo [3.3.0]octane derivative 38 (Scheme 11) [15]. In this transformation, the intermediate 39, formed by oxidative addition, leads to the cationic palladium-7r-allyl complex 40, which is finally converted to the isolated product 38 by regio- and diastereoselective nucleophilic addition of an acetate anion. The bicyclic product 38 is of interest as a building block for the synthesis of capnellene sesquiterpenes. 

The Simmons-Smith reagent undergoes a transannular reaction with cyclooctyne to give bicyclo[3.3.0]octane derivatives (547a). The reaction... 

The rearrangement of isopent-3-enyl epoxy esters with Cp2ZrCl2/AgC104 yields asymmetric bicyclo octane esters which are base-stable protecting groups for carboxylic acids (Scheme 48). However, the orthoesters are only the kinetic products and can rearrange under reaction conditions to more stable THF derivatives. 

In an asymmetric approach to the bicyclo[2.2.2]octane ring system, a double Michael addition has been employed using phenylmenthyl acrylate as the initial Michael acceptor. The condensation of the dienolate, generated with Lithium Diisopropylamide, reacts with the acrylate to afford the bicyclo[2.2.2]octane derivative (eq 6). The de for the reaction is only 50% however, it is highly endo selective (>95%). ... 

De Meijere and coworkers have also studied a number of other mono- and dicyclopropyl-substituted bicyclo[2.2.2]octane derivatives to compare with the results of their trihomobarrelene data. The relative rates below are for solvolysis in 80 % aqueous ethanol at 25°C. It is interesting to note here that the rate increases for substituting the... 

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