Bicyclic cyclooctenes

Alkylation of 28 with acrolein gives the bicyclic ketone (65), which can be converted to 4-cyclooctene-l-carboxylic acid by the action of base on its methiodide (55a). 

In determining whether a bicyclic system is large enough to accommodate a bridgehead double bond, the most reliable criterion is the size of the ring in which the double bond is located. Bicyclo[3.3.1]non-l-ene" (112) and bicyclo[4.2.1 ] non-l(8)ene (113) are stable compounds. Both can be looked upon as derivatives of tra 5-cyclooctene, which is of course a known compound. Compound 112 has been shown to have a strain energy of the same order of magnitude as that of... 

The reductive demercuration was marred by the loss of about half of the peroxide due to competing deoxymercuration which afforded 4-cycloocten-l-ol. An additional complication was the formation of a small amount of trans-1,2-epoxy-cw-cyclooct-5-ene. The bicyclic peroxide 50 was readily separated from the unsaturated alcohol by silica chromatography, but complete removal of the epoxide was more difficult. Preservation of the peroxide linkage was markedly higher in the bromodemercuration. The diastereoisomeric dibromoperoxides 51 were separated by HPLC, although only one isomer was fully characterised. 

These studies paved the way for numerous synthetic applications, in particular total syntheses. Thus, the low-tech PtCl2, PtCl4, or PtBr4 systems, as named by Fiirstner, proved superior and more reliable compared to Trost s TCPCtfe system288 for the reactions of the cyclooctene substrate as shown in Scheme 81.300 These reactions, which could be run in a multi-gram scale, proved useful, for instance, for the formal total synthesis of streptorubine B. Similarly, a formal total synthesis of roseophilin was devised, based on a nearly quantitative transformation of an enyne moiety into a bicyclic diene system (Scheme 81).301... 

On the contrary, a-lithiated epoxides have found wide application in syntheses . The existence of this type of intermediate as well as its carbenoid character became obvious from a transannular reaction of cyclooctene oxide 89 observed by Cope and coworkers. Thus, deuterium-labeling studies revealed that the lithiated epoxide 90 is formed upon treatment of the oxirane 89 with bases like lithium diethylamide. Then, a transannular C—H insertion occurs and the bicyclic carbinol 92 forms after protonation (equation 51). This result can be interpreted as a C—H insertion reaction of the lithium carbenoid 90 itself. On the other hand, this transformation could proceed via the a-alkoxy carbene 91. In both cases, the release of strain due to the opening of the oxirane ring is a significant driving force of the reaction. 

Another group of compounds that have a twisted double bond are the bicyclic compounds with bridgehead double bonds such as 1,2-norbomene (9) and 1,7-norbornene (10). " It has been found that many compounds, such as 11, which is based on trawi-cyclooctene, may be isolated whereas those based on smaller trauj -cycloalkenes are usually quite unstable. Some evidence for the formation of 9 has been obtained by trapping the product of the dehalogenation of 1,2-diha-lonorbornanes." Here, the simplest view is that the two p orbitals that form the double bond in 9 and 10 are roughly perpendicular to each other. However, pyr-amidalization and rehybridization also are involved. One indication is the reduced localized 7i-orbital population found in the NBO analysis. Whereas normal alkenes have 71 populations of 1.96 e, for 9 with OS = 57 kcal/mol, it is 1.921, and for 10 with OS = 86 kcal/mol, it is 1.896. With 9, the deviations of the a and n orbitals from the line of centers are 24° and 19°, respectively, and with 10, the deviations are 34° and 29°. 

The prochiral aziridine 1 is easily prepared from cyclooctene. Paul Muller of the University of Geneva has shown (Helv. Chim. Acta 2004,87,227) that metalation of 1 in the presence of the chiral amine sparteine leads to the bicyclic amine 3 in 15% , by way of intramolecular C-H insertion by the intermediate chiral carbene 2. The sparteine can be recovered and recycled. 

Alkenes participate readily in oxymercuration with increasing alkyl-substitution resulting in decreasing reactivity.489,491,492 The oxymercuration of alkenes is usually an anti process.493 195 Exceptions are strained bicyclic olefins, such as norbomene495,496 [Eq. (6.83)],497 and frans-cyclooctene and frans-cyclononene.494... 

This subject has recently been reviewed.647 Several additional papers have appeared on the catalytic oxidation of alkenes by 02 in the presence of PdCl(MeCN)2N02(148).64S Terminal alkenes and trans- cyclooctene yield the corresponding ketones, cyclopentene and cyclohexene the corresponding allyl alcohol, and bicyclic alkenes the corresponding epoxide. Heterometallacy-clopentanes such as (152) have been isolated from the reaction of (148) with norbornene (dicy-clopentadiene), and characterized by X-ray crystallography.6486 Glycol monoacetates were obtained from the reaction of (148) with terminal alkenes in acetic acid.649... 

The highly strained bicyclic frans-cyclooctenes, both twist (12) and chair (13) forms, are exceptions and are reported to react with phenyl azide to yield a single regioselective addition product (14 and 15, respectively) (Scheme 9).133... 

In the following years, a number of other monocyclic, bicyclic and polycyclic olefins including cyclobutene, [4] cyclopentene [3 a, 5] and cyclooctene [6] were found to undergo ring-opening polymerization. 

The pyrrolidine enamine of cyclohexanone (IX/1) treated with acrylaldehyde yields the bicyclic compound, IX/2, in 72 % yield in which the pyrrolidine ring has moved. On heating with aqueous base, the methiodide IX/3 was transformed to 4-cyclooctene-carboxylic acid (IX/4) [1], In a similar reaction, but without reorganisation of the substituents, 2-nitrocyclohexanone (IX/5) was... 

One of the most popular methods for creating the anatoxin-a skeleton is by transannular cyclization of a suitably substituted cyclooctene. This approach was used in the first synthesis of racemic anatoxin-a (Campbell et al. 1979). They carried out two different methodologies in order to reach the 9-azabicyclo[4.2.1]nonane structure (Scheme 7.3). The 1,5-cyclooctadiene (10) starting compound was transformed into the methyl amine 11 which was treated with hypobromous acid to produce the desired bicycle 12 as a mixture of diastereoisomers in 29% overall yield, with some amount of the azabicyclo[3.2.1] analogue (Bastable etal. 1972). 

The syn addition of iodine azide has been observed with a strained cyclobutene derivative29. Anomalous products were obtained from (i )-cyclooctenes and bicyclic (-E -cyclooctenes30,3I, e.g., 5-7. From 1,5-cyclononadiene and 1,5- and 1,6-cyclodecadiene, stereoselective transannu-lar cyclization occurred, involving acetonitrile (solvent) as the nucleophile to give 8--1032. From 1,3-dienes, benzofuran and A-acylindoles were obtained 1,2- or 1,4-diazides via the corresponding iodo azides (Section 7.2.2.4.). 

The highly strained twist" and chair bicyclic trans-cyclooctenes 17 and 18 underwent an exceptionally regioselective and diastereoselective cycloaddition with phenyl azide, the stereochemistry of the dihydrotriazoles was fully retained in the thermal decomposition to aziridi-nes107. Furthermore no imine is produced. 

Isomerization of cyclooctene oxide. Isomerization of cyclooctene oxide (1) with lithium diethylamide gives the bicyclic alcohol (2) and 3-hydroxycyclooctene (3) in the approximate ratio of 4 1 (2, 247). The abnormal product (2) is obtained only with medium-ring epoxides large-ring epoxides give exclusively allylic alcohols. Sheng1 finds that cyclooctene oxide can be isomerized exclusively to 3-hydroxycyclooctene (3) if... 

Transannular participation of n-bonds takes place in the solvolysis of esters of (Z)-cyclooct-3-enol to give bicyclic derivatives containing three-membered rings. Thus, acetolysis of 4-(4-bromophenylsulfonyloxy)cyclooctene followed by hydrolysis of the product mixture gave endo-and exo-bicyclo[5.1.0]octan-2-ol (1), in 39 and 13% yield, respectively. The predominant formation of the cntfo-bicyclooctanol is consistent with a concerted process. ... 

Group Migration Reactions.- Direct irradiation of cyclooctene (la) in pentane brings about CIS -trans isomerization as well as the formation of the bicyclic products (2a) and (3). These are formed via the carbene intermediates (4) and (5). The latter carbene (5) also affords methylenecycloheptene. cis -trans -Isomerization also arises with the cycloalkenes (lb) and (Ic). Product (2b) is formed from cyclodecene (lb) and... 

The trons-cycloalkenes 37a, 67, and trans-cyclononene 227 react with diironnonacarbonyl 228 to form the tetracarbonyliron(O) complexes 229-231 with the frans-cyclooctene complex 229 being significantly more stable than that of trons-cyclodecene 231 (177). The bicyclic triene 232 reacts with 228 preferentially at one of the trans double bonds of the trans, trans- cy-clodecadiene substructure. In line with the expected stability, the trans, cis-cycloocta-1,5-diene 234 and trans, ris-cycloocta-1,3-diene 236 react with 228 exclusively at the trans double bond to give the complexes 235 and 237. In the complex 238, tetracarbonyliron(O) is bonded to the bridgehead double bond of bicyclo[4.3.2]deca-7,9-diene (184b) (177). 

Reaction with epoxides [1, 611, after line 2]. The reaction of epoxides of medium-size rings with lithium diethylamide is complicated. Thus m-cyclooctene oxide (I) gives mainly the bicyclic alcohol (2), and tra/i.s-cyclooctene oxide (5) gives mainly the epimeric bicyclic alcohol (6).38 Using deuterium tracer studies, Cope showed that the bicyclic alcohols (2) and (6) arise by loss of a hydrogen atom from an a-... 

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