Resolution of trans-cyclooctene

Cope s classical papers (45, 46) on the successful optical resolution of trans-cyclooctene (21) (Figure 9) demonstrate a way to desymmetrize the Djh symmetry of ethylene by trans bridging. In this molecule, the -(CH2)6- bridge is short enough to prevent interconversion between the enantiomeric C2 con-formers 21 23 through the loop-jumping mechanism. 

Use for resolution of cycloalkenes. W s-Cycloalkenes of intermediate size (Cg-Cjo) should be capable of existing in enantiomeric forms because of the inability of the trans double bond to rotate with respect to the remainder of the molecule. But in the absence of salt-forming groups, resolution cannot be accomplished by the usual methods of forming derivatives. However, Cope et al.s found that the strong tendency of an alkene to complex with a platinum compound provides an effective method of resolution. The complex of ethylene with platinous chloride and (+) or (-)-a-methylbenzylamine exists in only one form since ethylene is symmetrical. But addition of the base to a solution of the platinum complex of trans-cyclooctene opens the way for formation of the diastereoisomeric complexes derived from the R- and S-forms of the base. Fractional crystallization at —20° (liquid at 25°) effected separation. Liberation of the (—)-hydrocarbon from the complex with potassium cyanide gave a product of aD — 411°. 

The enantiodifferentiating protonation by aminoalcohols was further utilized in the partial kinetic resolution of rrarcs-l-acetylcyclooctene (26), which is formed by irradiation of the cis cyclooctene 25 (Scheme 10) [43,44]. The trans alkene is stable in carefully dried acetonitrile. Protic species catalyze the isomerization back to the cis alkene. When the irradiation was carried out in the presence of (+ )-ephedrine, a new CD signal appeared that was assigned to the trans alkene... 

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. 

As already indicated, trans-cycloalkenes such as trans-cyclooctene are so strained that the complete lack of conformational equilibrium induces the existence of two enantiomeric structures at room temperature. Tl ans-acetyl-cyclooctene (t-ACO) can be produced from the cis isomer in a photostation-ary equilibrium. In the presence of chiral catalysis, we will describe one interesting example of kinetic resolution of unstable t-ACO. 

Strained trans-cycloalkene derivatives such as t-cyclooctene are chiral molecules which can be isolated in pure enantiomeric form. Owing to its high reactivity, resolved t-24 should not normally be isolable. However, an interesting example of a kinetic resolution of t-24 was reported recently [63]. 

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. ... 

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