Substituents axial

The greater stability of an equatorial methyl group compared with an axial one IS another example of a steric effect (Section 3 2) An axial substituent is said to be crowded because of 1,3 diaxial repulsions between itself and the other two axial sub stituents located on the same side of the ring... 

Diaxial repulsion (Section 3 10) Repulsive forces between axial substituents on the same side of a cyclohexane nng... 

Strong 1 3 interactions between the axial substituent at C-6 with 8j5- and 2ji (5a-series) hydrogens and 10 -substituents decrease the reactivity of the 6-ketone as compared to saturated 3-ketones. The 6-ketone does not react with methanol to give a dimethyl ketal, even in the absence of the C-19 methyl group. Thus the 19-nor-5a-3,6-dione (75) gives selectively the 3,3-dimethyl-ketal (76). ... 

The rotation of an axial CHjI group [cf. (3)] in a polycyclic saturated system is severely hindered by axial substituents on the same face therefore preferred orientations for both an 18- (Figure 12-1) and I9-CH2I (Figure 12-2) in steroids can be written ... 

Draw the possible conformations, and calculate the strain energy in each.. Remember that equatorial substituents cause less strain than axial substituents. 

Chair cyclohexanes are conformationally mobile and can undergo a ring-flip, which interconverts axial and equatorial positions. Substituents on the ring are more stable in the equatorial position because axial substituents cause 1,3-diaxial interactions. The amount of 1,3-diaxial steric strain caused by an axial substituent depends on its hulk. 

Ring-flip (Section 4.6) A molecular motion that converts one chair conformation of cyclohexane into another chair conformation. The effect of a ring-flip is to convert an axial substituent into an equatorial substituent. 

Intramolecular hydrogen-bonds can increase the stability of certain conformations. For example, dianhydrides that contain fJ-L-Sorp or ct-D-Frup in the 5C2 conformation have the C-4 hydroxyl group in a 1,3-diaxial relationship with 0-2, which permits the formation of an intramolecular hydrogen bond. This might, in part, offset the destabilizing influence of three or two axial substituents, respectively. This effect is decreased in hydrogen-bonding solvents. 

TABLE 4.3 Free-Enei Differences between Equatorial and Axial Substituents on j Cyclohexane Ring (A Values)... 

Co within all compounds of the so-called cobalamin (or B12) family. The biological functions of cobalamin cofactors are defined by their axial substituents either a methyl or an adenosyl group. Both cofactors participate in biosynthesis the former in methyl transfer reactions while the latter is a free radical initiator, abstracting H atoms from substrates. Decades after their initial characterization, the fascination with the biological chemistry of cobalamins remains.1109... 

A number of these dyes were applied, mixed with a polymer for the control of the aggregation state, to CD-R and DVD-R recording systems. The aggregation state in the recording layer was controlled by choosing the set of axial substituents (Scheme 8 R1, R2, and R3). The interaction between the phthalocyanine dyes and the polymers was dependent on the length of the axial substituents or, more carbon atoms in the alkyl group were found to be necessary for the axial substituents to mix with the polymers.218... 

Structural studies of the initial diazaphosphorinanes and their complexes revealed a close connection between the structure of the former and the number of coordinating borane molecules. When substituents of a diazaphosphorinane with R = Ph are equatorial, addition of three molecules of borane in the axial position is not energetically favorable. In the case of R = CH2Ph there is a form with one axial substituent hence the third molecule of borane may approach the equatorial nitrogen lone electron pair (89IZV1375). 

A comparison of the structures of products and initial 1,3,5-diazapho-sphorinane reactants reveals a correlation between the number of added borane molecules and the predominant conformation of the initial compounds. l,3-Dibenzyl-5-phenyl-l,3,5-diazaphosphorinane (45) adopts a chair conformation. The substituents at the phosphorus atom and at one of the nitrogen atoms are equatorial, and another nitrogen possesses an axial substituent. In other 1,3,5-diazaphosphorinanes, all the substituents are equatorial. The number of borane molecules added is likely to be determined by the same factors as their conformational stability. There is steric hindrance when the three BH3 groups are axial. 

In this scheme, a highly puckered metallocycle was envisioned, possessing pseudoaxial and equatorial substituents, and reaction pathways were said to be favored which minimized the following effects (a) 1,3-diaxial interactions of substituents on the two a-carbons (b) axial substituent interactions with juxtaposed ring carbons and (c) 1,2-diequatorial interactions. This scheme predicts relatively nonstereospecific metathesis of rra/j.v-olefins but highly stereospecific metathesis of ra-olefins. For example, the following pathways for reactions of m-olefins were proposed ... 

We shall consider here in more detail two models first a dynamic coupling approach, due to Weigang33, who considered optical activity deriving from the coupling of electric dipoles (the diene chromophore and the polarizable bonds around it) and second, a localized orbital investigation, which permits one to separate the contributions from the intrinsic diene optical activity and from the axial substituents. 

It is apparent that on increasing the polarizability of the allylic axial substituent, the Cotton effect becomes stronger. If we refer to the nearest double bond, however, the chirality defined by the C—X bond is negative, thus we should expect a decrease of Ae. Only by considering the diene as a whole (diene-picture), as depicted in the lower part of Figure 7(b), can one justify the reported trend. 

Another, very notable, case where the two definitions are in conflict is that of het-eroannular cisoid dienes. As we have mentioned, this was just the class of molecules that stimulated the introduction of the AAR. Here, in order to have the correct results one should refer the chirality of the axial substituent to the individual double bonds (olefin-picture), as depicted in Figure 6 and in the upper parts of Figure 7(b) and (c). The case of heteroannular dienes is anyway peculiar, because in these compounds the chromophore is unusually distorted. This case is treated in the following section. 

Dienes in quasi-s-fraws conformation are found only in cyclic structures where perfect planarity is hindered. The DR also holds valid for this kind of conformation, as demonstrated by the considerations of Section II.D.l.a and also confirmed by all the reported calculations. Indeed, contrary to what is sometimes found for cisoid systems, the rotational strength evaluated by many types of calculation is invariably found to follow the diene rule for transoid systems. However, very small skew angles are usually found in real molecules and this implies that the main contribution to the observed optical activity cannot come from the weak intrinsic distortion, but is more likely to stem from the dissymmetric perturbations, notably of the allylic axial substituents. 

The intrinsic contribution, accounted for by the diene rule, seems to be easily outweighed by the perturbations arising from the allylic axial substituents, which in turn define the allylic axial chirality rule. This latter can be formulated in two ways The olefin-picture , where chirality is referred to the nearest double bond, and the diene-picture ,... 

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