Dioxane diaxial interaction

Also, 2,2,3,6-tetra-Me-5-Cl-l,3-dioxan, due to 1,3-diaxial interactions, prefers the 2,5-twist-boat form (76BSF563) the same conformation was reported for the stereoisomeric 2-Ph-4-(2 -furyl)-5-N02-6-Me-l,3-dioxanes and 2,2,6-tri-Me-4-(2 -furyl)-5-N02-l,3-dioxanes (75MI2), for 2-Alk-2,4,4-tri-Me-l,3-dioxane derivatives (78KGS1172) and for the cis isomers of 2-OR-4-Me-l,3-dioxane (R = Et, nPr, /Pr, nBu, n-CsHn) (81DOK116). The corresponding trans isomers adopt the chair conformation with di-eq substitution. The isomeric 2-OR-4,4-di-Me-l,3-dioxanes also prefer the 1,4-twisted-boat conformer (81DOK116). 

The presence of twist-boat forms in the conformational equilibria of 1,3-dioxane derivatives due to the presence of 1,3-diaxial interactions was corroborated by force field calculations [77T2237 79T691, 79T1945]. 

Haworth formulas) to form the dioxane derivative (65), rather than (64), which would have a 1,3-diaxial interaction between the aldehyde and methoxyl groups. The conformational changes involved in typical reactions of periodate-oxidized methyl a-D-glucoside are detailed in Fig. 1. 

This expression of the anomeric effect is based on the assumption that the steric influence of the substituent on the tetrahydropyran ring is the same as that on cyclohexane. However, the assumption may not be generally true, because the C-O bond is shorter than the C-C bond, and this leads to a larger s n-diaxial interaction in the heterocycle, as has been demonstrated experimentally in 1,3-dioxane systems. ... 

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. 

These differences are reflected in the A values for groups attached to cyclohexane analogues. Table 2.16 shows a number of A values for groups attached to various positions on heterocycles relative to cyclohexane. Note the dramatic difference between the 2- and 5-positions on 1,3-dioxane. This difference reflects the shorter C-Obond lengths, making the 1,3-diaxial interactions more repulsive. 

It has now become clear that in the 1,3-dioxane series 17 certain compounds in which a chair conformation would require 1,3-syw-diaxial methyl groups, prefer a twist conformation n ). Unfortunately the 1,3-interactions which favour the twist conformation also lower barriers to interconversion, so that no direct nmr evidence or barriers have been obtained. 

The initially proposed explanation for the anomeric effect as a simple dipole-dipole interaction [12] therefore accounts for only a part of the effect, but it does not represent the whole story. If one calculates the electrostatic interaction energy in frans-2,5-dichloro-l,4-dioxane (Fig. 2.9) (the molecular geometry is known from X-ray analysis) using the values of ji = 2.2 and 1.4 D for the dipole moments of C-Cl and C-0 bonds and e = 2.3 for the dielectric constant, one arrives at the energy difference of about 1 kcal/mol in favor of the diaxial form [36]. This difference is clearly too small to account for a strong preference for the diaxial conformation [37]. 

---