Past exam of the chemistry B course of the University of Cambridge / 2024 / Paper 1 / B3 / c / ii

The axial penalties depend on the ring position. An axial methyl at C2 encounters the axial hydrogens on C4 and C6. The short C–O links and dioxane geometry make these 1,3-Diaxial interactions particularly unfavorable. In contrast, an axial substituent at C5 points toward ring oxygens O1 and O3 rather than toward axial C–H groups at those positions. Those oxygen sites present much less steric obstruction than axial hydrogens on carbon.

Avoiding the expensive axial C2 methyl outweighs the cost of axial tert-butyl at C5. Transferring cyclohexane tert-butyl preferences unchanged would therefore give the wrong answer. This is primarily a position-dependent steric comparison, not the usual anomeric preference for an axial electronegative substituent at an acetal carbon. Primary NMR work on substituted dioxanes documents this axial C5 tert-butyl conformer.^[ref]