Cyclohexane derivatives, % axial

In the case of the cyclohexane derivative 7 however, that bears an equatorial acetate group, two axial cis-/3-hydrogens are available, and elimination in both directions is possible. The pyrolysis of 7 yields the two elimination products 8 and 6. Formation of product 8 is strongly favored, because the new double bond is in conjugation to the ester carbonyl group. ... 

Comparative Fequatorial groups in cyclohexane derivatives (and steroids) are more strongly retained than axial derivatives... 

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. 

A more subtle example of identical functional groups with different steric enviroment is found in the intermediate H which Corey [8] uses in the synthesis of fumagillin (13). The two identical secondary hydroxyl groups in the cyclohexane derivative H can be differentiated by using a bulky reagent since the axially disposed hydroxyl group is less accesible than the one which is equatorially disposed and can be chemoselectively methylated (12) in the presence of sodium rert-amylate (Scheme 12.2). 

This technique was used to synthesize some cyclohexane derivatives by substitution with electrophiles specifically in the axial or equatorial position. Whereas alkylation with dimethyl sulfate occurred smoothly, alkylation with haloalkanes failed completely. Rather nonstereoselective protonation of the lithium compound, as well as dehydrogenation to enol ethers, occurred. Operation of single electron transfer processes are believed to account for these results27. 

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

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. 

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. 

The equilibrium constants derived from the 31P NMR spectra at temperatures below coalescence show that there is a considerable predominance of the axial conformer of 2-diphenylphosphinoyltetrahydrothiopyran (Table 26) which contrasts with the equatorial preference in the corresponding cyclohexane derivative. This result indicates a strong anomeric effect, estimated at 2.40 kcal mol-1. The corresponding data for the anancomeric cis and trans 4-/-butyl derivative at chemical equilibration are presented in Table 26. The large difference in AG° at 173 and 323 K is compatible with a significant entropy effect, calculated AS° = +4.8 0.7 cal K.mol-1, with... 

As was the case for cyclohexane derivatives, the chair conformer that has the larger groups equatorial is usually more stable. Therefore, the chair conformers shown in Figure 25.2, which have most or all of the larger substituents equatorial, are more stable than the conformers obtained by ring-flips. The a- and /3-anomers differ only in the stereochemistry of the groups at the hemiacetal carbon. In the a-anomer the hydroxy group on this carbon is axial, and in the /3-anomer it is equatorial. 

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. 

Fig. 2-10. Ring inversion of a monosubstituted cyclohexane derivative equatorial substituents become axial and vice versa.

What do you think would happen if a cyclohexane derivative underwent an Sn2 reaction If the conformation of the molecule is fixed by a locking group, the inversion mechanism of the S j2 reaction, means that, if the leaving group is axial, then the incoming nucleophile will end up equatorial and vice versa. 

Standard free energy change for the axial-equatorial equilibrium in monosubstituted cyclohexane derivatives (from [103])... 

Figure 4.1-12 Characteristic frequencies of C-X bonds (X = Cl, Br, I) in hydrocarbons P primary, S secondary, T tertiary C atom, the subscripts denote the atoms in trans (antiperiplanar) position to the C-X bond. For cyclohexane derivatives Sh h stands for an axial, Sqc for equatorial C-X bond (Schrader and Meier, 1975).

Corey and coworkers have outlined the wide usefulness of N.N-dimethvl hydrazones (DMH) in synthesis.25-9 The parent carbonyl compounds can be regenerated by oxidative hydrolysis via periodate at pH 7 or with the very mild cupric acetate in water-THF. Metallation of these hydrazones selectively occurs at the less alkylated carbon. Alkylation occurred axially in the cyclohexane derivatives studied. Quenching of the metallated DMH s... 

On the laboratory scale, the tendency of elemental fluorine to initiate radical chain reactions resulting in tar formation can be controlled by appropriate choice of solvent. The solvent system CFCI3/CHCI3, sometimes with additional 10% ethanol, serves as an effective radical scavenger. The reaction enthalpy is controlled by dilution of the substrate in this solvent, by dilution of the fluorine gas with nitrogen or helium, and by use of a low reaction temperature. Under these conditions, the selective fluorination of cyclohexane derivatives in the tertiary axial position is possible in reasonable yields [16] (Scheme 2.4), supposedly by an electrophilic mechanism. 

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