= Solution
\b[E, with the axial anomeric <acetate>, hydrolyses faster.] The tert-butyl <substituent> strongly favours the chair in which it is equatorial, so the two <substrate (chemistry)>s cannot freely interchange axial and equatorial <acetate> simply by an inexpensive <ring inversion>. <protonation> activates the anomeric acetoxy leaving group. As its C–O bond cleaves to release <acetic acid>, a <lone pair> on the endocyclic <oxygen> donates into the developing anomeric orbital, producing an <oxocarbenium ion>. <water> attacks that <carbon>, and <deprotonation> gives the cyclic <hemiacetal>. Attack from either face accounts for the unspecified anomeric configuration of OH in the <product (chemistry)>.
The axial C–OAc bond in E can adopt <antiperiplanar geometry> relative to an endocyclic <oxygen> <lone pair>. This favourable $n_O\rightarrow\sigma^*_{C-O}$ interaction assists departure in the ionization <transition state>. The corresponding bond in F is poorly aligned in its preferred chair; achieving comparable overlap requires an unfavourable chair change, placing tert-butyl axial, or substantial ring distortion. The distinction is <stereoelectronic control of acetal hydrolysis>, rather than merely counting steric crowding in the <product (chemistry)>s.
An axial <acetal> can itself receive ground-state stabilization from the anomeric effect, so “axial means unstable” is not an adequate rate argument. What matters is the relative <Gibbs energy of activation> for the departing bond and the geometry of lone-pair assistance. Conformationally locked model <acetals> experimentally demonstrate faster <acid (chemistry)>-catalysed cleavage of the axially oriented <isomer>, although their numerical rate ratios should not be transferred to these different <substrate (chemistry)>s.<Stereoelectronic control of the hydrolysis of a conformationally locked acetal by Anthony J. Kirby and Robert J. Martin>[1983, abstract and pp. 1627–1632, acid-catalysed axial/equatorial comparison]{ref}
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