Cyclohexane derivatives conformation

Incorporation of stereogenic centers into cyclic structures produces special stereochemical circumstances. Except in the case of cyclopropane, the lowest-eneigy conformation of the tings is not planar. Most cyclohexane derivatives adopt a chair conformation. For example, the two conformers of cis-l,2-dimethylcyclohexane are both chiral. However, the two conformers are enantiomeric so the conformational change leads to racemization. Because the barrier to this conformational change is low (lOkcal/mol), the two enantiomers arc rapidly interconverted. 

According to this concept, the aldol condensation normally occurs through a chairlike transition state. It is further assumed that the stmcture of this transition state is sufficiently similar to that of chair cyclohexane to allow the conformational concepts developed for cyclohexane derivatives to be applied. Thus, in the example above, the reacting aldehyde is shown with R rather than H in the equatorial-like position. The differences in stability of the various transition states, and therefore the product ratios, are governed by the steric interactions between substituents. 

Thiourea canal inclusion compounds 19 26) have a wider diameter than those formed by urea, such that n-alkanes are not included but that molecules of cross-section approximately 5.8-6.8 A are trapped 64). Thus many inclusion compounds have been reported between thiourea and branched alkanes or cyclic molecules. Of special interest are the inclusion compounds with cyclohexane derivatives and the recent studies carried out on the preferred conformation(s) of the ring in the restricted environment of the thiourea canal. 

In cyclic systems, the usual simple requirements of Saytzev or Hofmann rules may be overridden by other special requirements of the system, e.g. the preference for elimination from the truns-diaxial conformation in cyclohexane derivatives (cf. p. 255). Another such limitation is that it is not normally possible to effect an elimination so as to introduce a double bond on a bridgehead carbon atom in a fused ring system (Bredt s rule), e.g. (47) (48) ... 

In cyclohexane derivatives at least six different salient orientations of 8-carbons with respect to a perturbing substituent X are conceivable (Scheme 7). Of these, the one shown last is quite different from all the others, in that the substituent X is very close in space to the syn-axial carbon under observation. The symbol (sa for syn-axial) is used for the 8-interaction in this conformation. 

Other examples of the formation of six-membered rings by means of an intramolecular alkylation of an ester enolate are given in Table 7. Entry 6, i.e., stereoselective transformation of the epoxy ester into the cyclohexane derivative, should be discussed briefly as a representative for the other cases. The probable reason for the unexpectedly high selectivity i.e., the nonappearance of the diastereomer 8, can be demonstrated by the two transition-state-like conformations 9 and 10. 9 displays a very severe 1,3-diaxial interaction in comparison to 10, thus, formation of the diastereomer 7 from conformation 10 is highly favored113. 

D Cis-Trans Isomerism and Conformational Equilibria for Cyclohexane Derivatives... 

The cis-trans isomerism of cyclohexane derivatives (Section 5-1 A) is complicated by conformational isomerism. For example, 4-tert-butylcyclohexyl chloride theoretically could exist in four stereoisomeric chair forms, 1, 2, 3, and 4. 

For cyclohexane derivatives to react in this way, the transition-state conformation must have both leaving groups axial ... 

Exercise 12-20 a. Consider that all of the following cyclohexane derivatives have R as a very large group so the conformations shown are the most stable ones. Which member of each pair would you expect to react more rapidly under the given conditions and why Draw the structure and configuration of the major product. (Review Section 8-8.)... 

Recently, Crabb, Turner, and Newton (68) have observed that perhydropyrido-[1.3]oxazine exists as a =9 1 mixture of the trans and the cis forms 97 and 98. The cis form 98 has two anomeric effects (-2.8 kcal/mol), two gauche forms of butane (1.8 kcal/mol) and one gauche form of -propyl ether (0.4 kcal/mol) whereas the trans form 97 has only one anomeric effect (-1.4 kcal/ mol). On that basis, the trans form 97 should be more stable than the cis form 98 by about 0.8 kcal/mol, in agreement with the experimental result. Katritzky and co-workers (69) have also shown that 1-oxa-3,5-diaza and 1,3-dioxa-5-aza cyclohexane derivatives exist respectively in the conformations 99 and 100. With an alkyl group in the axial orientation, both conformations gain two anomeric effects. 

For rings larger than the six-membered rings the problem is more complex, since it may be difficult to distinguish between large amplitude motion like the situation in many five-membered rings and a mixture of two or more conformers as in cyclohexane derivatives. 

When comparing two stereoisomeric cyclohexane derivatives, the more stable stereoisomer is the one with the greater number of its substituents in equatorial orientations. Rewrite the structures as chair conformations to see which substituents are axial and which are equatorial. 

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