Cycloalkenes optically active

As mentioned earlier, preparation of (Z),( )-l, 5-cyclooctadiene (31) in an optically active modification 2) first demonstrated the chiral nature of ( )-cycloalkenes. In this classical experiment, Cope and coworkers obtained ( + )-31 by the Hofmann elimination of the (-l-)-ammonium salt 30. They were also successful in obtaining (+)-31 by optical resolution of racemic 31 through complexing with a chiral Pt(II)... 

As was the case with chiral ( )-cycloalkenes, Cope and coworkers 62) were the first to prepare single-bridged allene in an optically active modification 63). 

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... 

Even a simple strained molecule can show conformational enantiomerism. trans-Cyclooctene is the smallest stable trans-cycloalkene, and it is strained. If trans-cyclooctene existed as a planar ring, even for an instant, it could not be chiral. Make a molecular model of trans-cyclooctene, however, and you will see that it cannot exist as a planar ring. Its ring is folded into the three-dimensional structure pictured in Figure 5-18. The mirror image of this structure is different, and trans-cyclooctene is a chiral molecule. In fact, the enantiomers of iran.v-cyclooclcnc have been separated and characterized, and they are optically active. 

The intramolecular Wittig reaction is very useful for the synthesis of cycloalkenes and heterocyclic rings. Thus, optically active phosphorane 4.24 on heating in toluene gave p-nitrobenzyl 2-methyl-(5J )-penem-3-carboxylate (4.25) in 89% yield . 

Chirality may exist in many molecules that do not possess a chiral center. Such compounds may possess a chiral plane or a chiral axis, and are said to be dissymetric with respect to either that plane or that axis. Certain optically active allenes, biaryls, alkylidenecyclohexanes, and spiranes provide examples of axially dissymmetric molecules (chiral axis), irons-Cycloalkenes exemplify planar dissymmetry in molecules. The configurations of these classes may be specified by the Cahn-Ingold-Prelog convention using the usual R and 5 descriptors. Special subrules, which we will not describe here, are applied to this purpose. The interested reader is referred to references 8 (see p. 43) and 9 for details. Scheme 2.1 presents some molecules that are optically active because of planar or axial dissymmetry, and for which the absolute configurations have been determined. 

The intramolecular enantioselective Rauhut-Currier reaction [295] generates optically active cycloalkenes from acyclic precursors bearing two tethered Michael acceptors. In 2(X)7, Miller et al. reported the first organocatalyzed intramolecular cyclization of symmetrical bis(a,P-unsaturated ketones) to afford in good yields... 

As was illustrated in Scheme 2.1, there are many molecules which are chiral but which do not contain chiral carbon atoms. The optical activity of such substances frequently depends upon the barrier to conformation changes which effect racemization. For example, the lowest energy path for racemization of fran -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 trans-cyclooctene, in which the rotation of the plane is about the C(8)-C(l) and the C(2)-C(3) bonds. 

It is known that although trans-cyclo-octene can be resolved and is optically stable, frans-cyclononene rapidly racemizes at room temperature. Marshall and his co-workers have now shown that optically active trans-ten- and eleven-membered 1,2-dimethylcycloalkenes (18) can be prepared, and are optically stable, proving that, as expected, substituents on the double bond increase the rotational ( jump rope ) energy barrier. However, the analogous twelve-membered cycloalkene racemizes at or below room temperature. In related studies, Fava, Lunazzi, and their co-workers have prepared 2-substituted nine-, ten-, and eleven-membered trans-thiacycloalk-4-enes (19) dynamic n.m.r. 

In spite of the thermal instability of the (E)-isomers, the enantiodifferentiating photoisomerization of smaller-sized cycloalkenes has been investigated to some extent. Photosensitization of (Z)-cyclohexene (13Z) with chiral benzene(poly)carboxylates affords trans-anti-trans-, cis-trans-, and cis-anti-cis-[2 + 21-cyclodimers (16). Interestingly, only the trans-anti-trans product is optically active, and the ee reaches up to 68% ee, for which the enantiodifferentiating photoisomerization of 13Z to optically active (El-isomer 13E and the subsequent stereospecific concerted addition to 13Z are responsible. In contrast, the cis-trans photoadduct is formed through the stepwise cyclization via a biradical intermediate, losing the original chiral information in 13E. ... 

Recent studies on enantiodifferentiating photoisomerization reveal that the photosensitization of C Cg (Z)-cycloalkenes with optically active aromatic esters affords chiral ( )-cycloalkenes in good to excellent ees. The mechanism involves enantiodifferentiating rotational relaxation within the exciplex intermediate formed from the excited singlet state of chiral sensitizer and prochiral substrate. The exciplex structure and hence the stereochemical outcome are very sensitive not only to the internal factors, such as sensitizer energy and structure, but also to the external entropy-related factors such as temperature, pressure, and solvent. This leads to a novel idea of multidimensional control of product chirality by several environmental factors. The asymmetric photosensitization can be applied to the photochemical asymmetric synthesis and also be used as a powerful tool for exploiting the reaction mechanisms in the excited-state chemistry. 

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