Leaving Group Effects on the Selectivity of the Silylation of Alcohols: The Reactivity–Selectivity Principle Revisited

TBS protection of primary alcohol naphthalen-1-ylmethanol (<b>4a</b>) and secondary alcohol 1-(naphthalen-1-yl)­ethanol (<b>4b</b>) has been studied under various reaction conditions. The primary/secondary selectivity is largest in the comparatively slow Lewis base catalyzed silylation in apolar solvents and systematically lower in DMF. Lowest selectivities (and fastest reaction rates) are found for TBS triflate <b>1b</b>, where only minor effects of solvent polarity or Lewis base catalysis can be observed

The Lewis Base-Catalyzed Silylation of AlcoholsA Mechanistic Analysis

Reaction rates for the base-catalyzed silylation of primary, secondary, and tertiary alcohols depend strongly on the choice of solvent and catalyst. The reactions are significantly faster in Lewis basic solvents such as dimethylformamide (DMF) compared with those in chloroform or dichloromethane (DCM). In DMF as the solvent, the reaction half-lives for the conversion of structurally similar primary, secondary, and tertiary alcohols vary in the ratio 404345:20232:1. The effects of added Lewis base catalysts such as 4-<i>N</i>,<i>N</i>-dimethylaminopyridine (DMAP) or 4-pyrrolidinopyridine (PPY) are much larger in apolar solvents than in DMF. The presence of an auxiliary base such as triethylamine is required in order to drive the reaction to full conversion