Size-dependent rate acceleration in the silylation of secondary alcohols: the bigger the faster

Abstract

Relative rates for the reaction of secondary alcohols carrying large aromatic moieties with silyl chlorides carrying equally large substituents have been determined in organic solvents.

The Size‐Accelerated Kinetic Resolution of Secondary Alcohols

“…In an appropriate model system for measuring the size‐dependence of reaction rates aromatic side chains should be increased systematically without adding unfavourable interactions (e.g. 1,5‐interactions) [21, 26] . That alcohols 1 a – d represent a suitable series for such a purpose is supported by the following characteristics: a) The calculated reaction free energies for the acylation with anhydride 2 were found to be almost identical for all four alcohols 1 a – d .…”

“…The first result is in agreement with the above‐mentioned mechanism for size selection. The comparatively low selectivity for the 9‐anthracenyl substituent is likely due to unfavourable 1,5‐interactions that have already burdened other systematic studies of size effects [21] . We therefore synthesized 1‐pyrenyl‐substituted DMAP derivative 7 as a possibly even more size‐selective catalyst (see SI).…”

“…1,5-interactions). [21,26] That alcohols 1 a-d represent a suitable series for such a purpose is supported by the following characteristics: a) The calculated reaction free energies for the acylation with anhydride 2 were found to be almost identical for all four alcohols 1 a-d. b) The same calculations indicate that the partial charge on the alcohol oxygen atom and the acidity of the hydroxy group is very similar for all four systems. c) Reaction rates for the acylation of alcohols 1 a-d with anhydride 2 are almost identical when using tri(n-butyl)phosphine (NBP, 6) as the catalyst (Figure 1 b).…”

“…The comparatively low selectivity for the 9-anthracenyl substituent is likely due to unfavourable 1,5-interactions that have already burdened other systematic studies of size effects. [21] We therefore synthesized 1-pyrenyl-substituted DMAP derivative 7 as a possibly even more size-selective catalyst (see SI). Repeating the acylation reactions of alcohols 1 a-d with anhydride 2 and catalyst 7 under otherwise identical conditions we find generally increased selectivities for all substrates, the largest selectivity for alcohol 1 d now amounting to approx.…”

“…Elimination of groups that induce steric hindrance and attraction is, unfortunately, linked to possible changes of electronic, kinetic and thermodynamic properties. Herein we present a different approach where the aromatic side chains of alcohol substrates are increased systematically such that no additional effective degrees of freedom are introduced [21] . It should be added that the term “effective” implies that the conformational space available to all substrates is practically identical and that the term “size” always refers to the dimensions of the aromatic side chains.…”