1,3-diaxial interaction/repulsion

Conformations in which there is a 1,3-diaxial interaction between substituent groups larger than Iqidrogen are destabilized by van der Waals repulsion. Equilibration of mixtures of cis- and /ran5-l,l,3,5-tetramethylcyclohexane reveals that the cis isomer is favored by 3.7 kcal/mol. This provides a value for a 1,3-diaxial methyl interaction that is 1.9 kcal/mol higher than that for the l,3-methyl-4iydrogen interaction. 

Closer examination of tetrahydropyrans 173 clearly reveals that two molecules of aldehyde 174 have been appended onto allylsilane 171 via a novel three-component coupling reaction. Marko et al. proposed the mechanism depicted in Scheme 13.61 [65], Formation of heterocycles 173 is described as a sequence of two processes an initial ene-type reaction [80] which leads to alcohol 177 via the chair-like transition state 176, in which both the aldehydic R-group and the OTMS substituent assume an equatorial position. The high regio- and stereoselectivity observed in this ene-reaction can be nicely explained by considering the stabilizing /(-silicon effect and the repulsive 1,3-diaxial interactions. Transition state 176 contains no 1,3-diaxial interactions and benefits fully from the stabilizing /(-silicon effect [81, 82] (for more detailed transition-state discussion see ref. [63]). 

F. Cortes-Guzman, J. Hernandez-Trujillo, G. Cuevas. The non-existence of repulsive 1,3-diaxial interactions in monosubstituted cyclohexanes. J. Phys. Chem. A 107, 9253-9256... 

Considering the factors favoring the CB conformation, it should be taken into account that the introduction of an endo-3 substituent (11) causes one of the CB forms (11a) to be destabilized by the resulting extra 1,3-diaxial interactions. Indeed, for each six-membered ring in the bicyclo[3.3.1]nonane skeleton, the second ring is equivalent to two axial substituents, the introduction of an endo-3 substituent being equivalent in this case to a third axial one. It leads not only to the absence in the equilibrium of the chair-chair conformation lib (which is mostly destabilized by the 3 - 7 repulsion) but also to the minor content of the chair-boat form 11a. The alternative boat-chair conformation 11c with the substituent in the bowsprit position dominates in this case (24,25). 

A methyl group at C-6 or C-ll favors the axial position as this minimizes interactions with the vinylic methyl group (for C-6) and steric repulsion with C-l (for C-ll). Methyl groups at C-7 and C-12 prefer an equatorial configuration since it is well known that 1.3 diaxial interactions are minimized. 

Figure 4.2.6 Two effects determine the configurations of open-chain carbohydrate derivatives (a) gauche confirmations are favored in 1,2-diols over anti conformations, and (b) 1,3-syn diaxial interactions between hydroxyl substituents are repulsive and often lead to distortions of the all-anti chain.

In (i) there are four 1,3-diaxial interactions between Br s and H s but there is relief of dipole-dipole repulsion. In (ii) there are no 1,3-diaxial interactions between Br s and H s, but there is increased dipole-dipole repulsion. Dipole-dipole repulsion and 1,3-diaxial interactions just about balance each other thus (i) and (ii) are of about equal stability. 

In each, there are both considerable 1,3-diaxial interactions and unrelieved dipole-dipole repulsion. Hence they are relatively unstable and do not occur in appreciable amounts in the equilibrium mixture. 

As is evident from the figure, the dominant van der Waals repulsion in the axial methyl conformer is between the methyl group and the axial hydrogens at C(3) and C(5). Interactions of this type are called 1,3-diaxial interactions. Substituents that are in a 1,3-diaxial orientation with respect to each other are said to be syn-axial. The... 

For an explanation of the stereoselectivity, the chair-like transition structures (52A and 52B) in which the mercury is chelated by the enolate o tygen and the aldehydic o tygen have been proposed by Machado et al. and Perrier and Middleton fScheme 12.141. This transition model would account for the observed stereoselectivity concerning the newly formed hydroxy group at C-5. In the transformation of 14 15a, while the transition structure 52A giving 15a has no severe steric repulsion, that of 52B giving the 5-epimer of 15a suffers 1,3-diaxial interactions. In the reaction of 53 45b, the favored transition structure would be 54B, giving 3,5-trans-isomer 45b as the major product... 

Conformations in which there is a 1,3-diaxial interaction between substituent groups larger than hydrogen are destabilized by van der Waals repulsion. Equilibra-... 

An important feature associated with heterocyclic rings is the reduction in steric repulsions for axial substituents that results from replacement of a methylene group in cyclohexane by oxygen, nitrogen, or sulfur. This effect is readily apparent in d5-2-methyl-5-r-butyl-l,3-dioxane, in which the preferred conformation has the r-butyl group axial and the methyl group equatorial. Divalent oxygen has no exocyclic substituents so the 1,3-diaxial interaction, which is the main unfavorable interaction for axial substituents in cyclohexanes, is not present. 

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