Cyclooctene racemization

Molecules that are chiral as a result of barriers to conformational interconversion can be racemized if the enantiomeric conformers are interconverted. The rate of racemization will depend upon the conformational barrier. For example, -cyclooctene is chiral. E-Cycloalkenes can be racemized by a conformational process involving reorienting of the... 

Introduction of the allene structure into cycloalkanes such as in 1,2-cyclononadiene (727) provides another approach to chiral cycloalkenes of sufficient enantiomeric stability. Although 127 has to be classified as an axial chiral compound like other C2-allenes it is included in this survey because of its obvious relation to ( )-cyclooctene as also can be seen from chemical correlations vide infra). Racemic 127 was resolved either through diastereomeric platinum complexes 143) or by ring enlargement via the dibromocarbene adduct 128 of optically active (J3)-cyclooctene (see 4.2) with methyllithium 143) — a method already used for the preparation of racemic 127. The first method afforded a product of 44 % enantiomeric purity whereas 127 obtained from ( )-cyclooctene had a rotation [a]D of 170-175°. The chirality of 127 was established by correlation with (+)(S)-( )-cyclooctene which in a stereoselective reaction with dibromocarbene afforded (—)-dibromo-trans-bicyclo[6.1 0]nonane 128) 144). Its absolute stereochemistry was determined by the Thyvoet-method as (1R, 87 ) and served as a key intermediate for the correlation with 727 ring expansion induced... 

F-Cyclooctene is chiral, and it was resolved into enantiomers by Cope and coworkers100 by separation of diasteromeric platinum complexes containing 20 and (+)-phenyl-2-aminopropane as ligands. Thermal racemization occurred around 150 °C with a rate... 

The photoisomerization of (Z)-cyclooctene (30) (Scheme 12) to the (E)-isomer (31) was sensitized by enantiopure alkyl benzenecarboxylates immobilized in zeolite to give modest ees. The use of an antipodal sensitizer pair of (R)-and (S)-1 -methyIheptyl benzoates, 32d and 32e, yielded enantiomeric 31 in — 5% and +5% ee, respectively, while the same sensitizers gave practically racemic 31 upon irradiation in homogeneous solutions. This small, but apparent, enhancement of the product ee observed upon irradiation in modified zeolite supercages is likely to arise from the decreased conformational freedom of the adsorbed sensitizer, the hindered approach of 30 to the sensitizer, and/or the different exciplex structure in confined media. In this context, it is interesting to examine the effect of temperature on the supramolecular photochirogenesis in modified zeolites and to compare the results with those obtained in the homogeneous phase. Such an examination will reveal the distinctly different role of entropy in confined media, which should be clarified in a future study. 

Hammond and Cole reported the first asymmetric photosensitized geometri-r cal isomerization with 1,2-diphenylcyclopropane (Scheme 2) [29]. The irradiation of racemic trans-1,2-diphenylcylcopropane 2 in the presence of the chiral sensitizer (R)-N-acetyl-1 -naphthylethylamine 4 led to the induction of optical activity in the irradiated solution, along with the simultaneous formation of the cis isomer 3. The enantiomeric excess of the trans-cyclopropane was about 1% in this reaction. Since then, several reports have appeared on this enantiodifferentiating photosensitization using several optically active aromatic ketones as shown in Scheme 2 [30-36]. The enantiomeric excesses obtained in all these reactions have been low. Another example of a photosensitized geometrical isomerization is the Z-E photoisomerization of cyclooctene 5, sensitized by optically active (poly)alkyl-benzene(poly)carboxylates (Scheme 3) [37-52]. Further examples and more detailed discussion are to be found in Chap. 4. 

Racemic (1 / A,3RiS )-3-methyl-1-phenyl-3,4,5,6-tetrahydro-l//-2,5-benzoxazocine-5-carbonitrile (35) crystallized as a racemic compound in an achiral space group.1 X-ray structure analysis showed that one of the enantiomers in the crystal was bent into the (retro,S)-TBC conformation (for torsion angles of the X-ray structure, see Fig. 18).1 TBC is a relatively rare d.v-cyclooctene conformation, and is the fourth and highest energy conformation for d.v-cyclooctene within an energy window of 33.4 kJ from the ground state.1 Selected FI and 13C solution-state and 13C cp/mas... 

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). 

Platinum complexes incorporating an optically active amine have been employed for resolution of racemic mixtures of optically active olefins by reaction of the olefin with dichloro-platinum(II). The differing solubility of the diastereoisomers permits separation by fractional crystallization and the olefin can be recovered by reaction of the complex with aqueous alkali cyanide. Using either (-f)-l-phenyl-2-aminopropane (Dexedrine) or (-f)- or (—)-a-phenyl-ethylamine. Cope and co-workers have resolved the optical isomers of trans double bond coordinated and, with (—)-phenylethyl-amine)dichloroplatinum(II), a bridged complex with each double bond coordinated to a different platinum atom. 

E -cyclooctene is subject to thermal racemization. The molecular motion allows the double bond to slip through the ring, giving the enantiomer. The larger and more flexible the ring, the easier the process. The rates of racemization have been measured for E-cyclooctene, Zf-cyclononene, and Zi-cyclodecene. For E-cyclooctene the half-life is Ih at 183.9° C. The activation energy is 35.6 kcal/mol. E-cyclononene, racemizes much more rapidly. The half-life is 4 min at 0° C, with an activation energy of about 20 kcal/mol. F-cyclodecene racemizes immediately on release from the chiral platinum complex used for its preparation. ... 

Certain planar and axially dissymmetric molecules can be racemized by processes that involve rotation about carbon-carbon single bonds. The lowest energy path for racemization of frans-cycloalkenes is a rotation of the plane of the double bond through an angle of 180 . This rotation is most easily seen by working with molecular models. It is represented below for the case of frans-cyclooctene, in which the... 

The ease of rotation will depend on the ring size. It is observed that trans-cyclooctene is quite stable to thermal racemization, and can be recovered with no loss in rotation after 7 days at 61°C. When the ring size is larger, it becomes easier for rotation of the plane of the double bond through the belt of the ring atoms to occur, and racemization takes place more readily. The half-life for racemization of trans-cyclononene is 5 min at 0°C. The resolution of /rans-cyclodecene has been accomplished using the techniques developed for irons-cyclooctene and trans-cyclononene, but it racemizes immediately on its release from the chiral platinum complex employed for its resolution. ... 

Traws-cyclooctene has been resolved, and its enantiomers are stable at room temperature. Traws-cyclononene has also been resolved, but it racemizes with a half-life of 4 min at 0°C. How can racemization of this cycloalkene take place without breaking any bonds Why does traws-cyclononene racemize under these conditions but fra s-cyclooctene does not You will find it especially helpful to examine the molecular models of these cycloalkenes. 

Ashworth IW, Miles JAL, Nelson DJ, Percy JM, Singh K. Trisubstituted cyclooctene synthesis at the limits of relay ring-closing metathesis a racemic difluorinated analogue of fucose. Tetrahedron. 2009 65(46) 9637—9646. 

Achiral ds-cyclooctene upon singlet sensitization yields chiral frcms-cyclooctene. While achiral sensitizers yield a racemic tra s-cyclooctene, chiral sensitizers yield enantiomerically enriched trans-cyclooctene (Scheme 23). ° The highest ee reported (73%) thus far is with optically active (-) tetramen-thyl-l,2,4,5-benezene tetracarboxylate at -110°C in diethyl ether. The extent of ee depends on temperature, pressure, and solvent. 

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