Cyclohexanes trans- ,2-diaxial

It has generally been assumed that phosphorous oxychloride-pyridine dehydrations, the elimination of sulfonates, and other base catalyzed eliminations (see below) proceed by an E2 mechanism (see e.g. ref. 214, 215, 216). Concerted base catalyzed eliminations in acyclic systems follow the Saytzelf orientation rule i.e., proceed toward the most substituted carbon), as do eliminations (see ref 214). However, the best geometrical arrangement of the four centers involved in 2 eliminations is anti-coplanar and in the cyclohexane system only the tran -diaxial situation provides this. 

The anti periplanar requirement for E2 reactions overrides Zaitsev s rule and can be met in cyclohexanes only if the hydrogen and the leaving group are trans diaxial (Figure 11.19). If either the leaving group or the hydrogen is equatorial, E2 elimination can t occur. 

It is believed that equatorial substituents such as chlorine or bromine would increase the guest diameter beyond the allowed values (assuming that the guest molecules stack roughly parallel to the canal68)). Support for this comes from the study of fluorocyclohexane where the population of the axial conformer is not enhanced to any major extent70. Nitro-71) and cyano-cyclohexane, trans-l,2-dichloro-, trans-1,2-dibromo-, tram-1,4-dichloro-, trans-1,4-dibromo-, and trans-l-bromo-4-chloro-cyclohexane all pack most efficiently in the thiourea canals as the axial or diaxial conformer 68,72. Tram-2,3-dichloro-1,4-dioxane behaves similarly73. In contrast isocyanato-, tram-1,4-diiodo-, trans-1 -bromo-4-iodo-, and tram-1 -chloro-4-iodo-cyclohexane are present as mixtures of the axial/equatorial or diaxial/diequatorial conformations as appropriate 68,72). The reason for this anomalous behaviour of the iodosubstituted cyclohexanes is not clear. 

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 trans-diaxial conformation in cyclohexane derivatives (c/. 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) ... 

Almost all cyclohexane systems are most stable in the chair conformations. In a chair, adjacent axial positions are in an anfi-coplanar arrangement, ideal for E2 eliminations. Adjacent axial positions are said to be in a tran -diaxial arrangement. E2 reactions only proceed in chair conformations from... 

Stereochemistry No preferred conformation Anti-periplanar elimination (trans-diaxial in cyclohexanes)... 

Trans-diaxial elimination (Section 9.3) Elimination of axial groups on adjacent atoms on a cyclohexane ring. This is the preferred geometry for the E2 reaction with cyclohexane derivatives. 

Nearly all cyclohexanes are most stable in chair conformations. In the chair, all the carbon-carbon bonds are staggered, and any two adjacent carbon atoms have axial bonds in an anti-coplanar conformation, ideally oriented for the E2 reaction. (As drawn in the following figure, the axial bonds are vertical.) On any two adjacent carbon atoms, one has its axial bond pointing up and the other has its axial bond pointing down. These two bonds are trans to each other, and we refer to their geometry as trans-diaxial. 

In a chair conformation of a cyclohexane ring, a trans-diaxial arrangement places the two groups anti and coplanar. 

In conclusion, with substituted cyclohexanes, E2 elimination must occur with a trans diaxial arrangement of H and X, and as a result of this requirement, the more substituted alkene is not necessarily the major product. 

Trans diaxial (Section 8.8B) In an elimination reaction of a cyclohexane, a geometry in which the P hydrogen and the leaving group are trans with both in the axial position. 

Acid-catalyzed hydrolysis of a 1,2-epoxycyclobexane produces a trans-diaxial 1,2-diol. What product would you expect to obtain from acidic hydrolysis of cis-S-iert-butyl-1,2-epoxycyclohexane (Recall that the bulky teri-butyl group locks the cyclohexane ring into a specific conformation.)... 

The most potent members of all of these series of decalin-derived molecules have anti-planar Tg stereochemistry. In the series of cyclohexane-derived compounds (231), the XRy2Ii)-trans compound was an extremely weak muscarinic and the ( )-cis-isomer was completely inert (275). Casy (256) suggested that an energetically unfavored trans-diaxial conformer (antiplanar Tg) for structure (231) may be the pharmacologically active form of the molecule. However, introduction of at-bu-tyl group into the cyclohexane system to sta-... 

E2 elimination requires that the H and the leaving group be anti-coplanar in a chair cyclohexane, this requires that the two groups be trans diaxial. However, when the bromine atom is in an axial position, there are no hydrogens in axial positions on adjacent carbons, so no elimination can occur. 

The stereochemical requirement of E2 elimination is anti-coplanar in cyclohexanes, this translates to trans-diaxial. Both dibromides are trans, but because the r-butyl group must be in an equatorial position, only the left molecule can have the bromines diaxial. The one on the right has both bromines locked into equatorial positions, from which they cannot undergo E2 elimination. 

When E2 eliminations occur in cyclohexanes, the leaving group and the (3-H to be removed must have a 1,2-trans diaxial relationship. So. first, draw the two possible chair conformations for each starting compound, and analyze the one in which the Cl leaving group is axial. 

Coupling is a through-bond phenomenon, as we know from the couplings in cis and trans alkenes, where trans alkenes have much larger coupling constants as their orbitals are perfectly parallel. Another case of perfectly parallel orbitals occurs with trans-diaxial protons in cyclohexanes. Typical coupling constants are 10-12 Hz for trans-diaxial protons, but much smaller (2-5 Hz) for axial/equatorial and equatorial/equatorial protons. 

The mechanism of dehydrohalogenation under basic conditions of trons-fused bicyclo[4,n,0]alkane halohydrins (563)—(565) has been studied. Three reaction types are noted (i) epoxide formation, (ii) ketone formation, and (iii) ring contraction. trans-Diaxial chlorohydrins corresponding to (563)—(565) gave epoxides (566)—(568) with relative rates (derived from bimolecular rate constants) of 1 3 17. This rate sequence was rationalized in terms of deformation of the cyclohexane ring brought about by the nature of the fused ring. In particular, deformation is probably towards the half-chair conformation favoured by the cyclohexane epoxide which is formed in the slow step. trans-Diequatorial chlorohydrins represented by (563)—(565)... 

If this principle is taken to its ultimate conclusion, there should be halo-cyclohexanes for which an E2 reaction is impossible. 2,6-Dimethyl-l-bromocy-clohexane (34) is such a case. To satisfy the relative stereochemistry of the two methyl groups (cis to each other) and the bromine anti to the two methyl groups), the bromine atom must be axial in one chair conformation with two axial methyl groups (34A), but equatorial in the other chair conformation that has two equatorial methyl groups (34B). Only conformation 34A has an axial bromine atom required for an E2 reaction, but both P-hydrogen atoms (Hg and Hb) are equatorial. No P-hydrogen atoms are trans, diaxial to an axial bromine, so there is no E2 reaction. When 34 is heated with ethanol KOH, there is no E2 reaction. The carbon bearing the bromide in 34 is very sterically hindered, so an Sn2 reaction is very unlikely certainly the substitution will be very slow. 

In E2 elimination reactions involving cyclohexane rings, why is it critical that the p-hydrogen and the leaving group be trans diaxial to one another ... 

Addition of chlorine or bromine to cyclohexene and its derivatives gives a trans diaxial product because only axial positions on adjacent atoms of a cyclohexane ring are anti and coplanar. The initial trans diaxial conformation of the product is in equilibrium with the trans diequatorial conformation, and in simple derivatives of cyclohexane, the trans diequatorial conformation is more stable and predominates. Because the original bromonium ion can form on either face of the double bond with equal probability, both trans enantiomers are formed as a racemic mixture. 

Let us consider the bromination of (i )-4-f rf-butylcyclohexene. Recall that in derivatives of cyclohexane in which interconversion between one chair conformation and the other is not possible or is severely restricted, the trans diaxial product is isolated. If a cyclohexane ring contains a bully alkyl group, such as fert-butyl (Section 2.6B), then the molecule exists overwhelmingly in a conformation in which the fert-butyl group is equatorial. Reaction of bromine with enantiomerically pure (R)-4-fert-butylcyclohexene occurs at both faces of the six-membered ring. Because bromine atoms must add in an axial manner, each bromonium ion intermediate reacts with bromide ion to give the same product. In the favored chair conformation of this product, fert-butyl is equatorial, the bromine atoms remain axial, and only a single diastereomer is formed. 

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