The sugar derivatives used for SHJ reactions should be purified, dried, and powdered before use. Intramolecular Friedel-Crafts reaction of the aromatic ring of a benzoate ester at the 2-position of 1-acetoxy ribose in the presence of a Lewis acid has been observed, and represents a potential side reaction. Heterocycles must not be too basic in order to avoid excessive complexation with the Lewis acid; amino-substituted heterocycles such as cytosine, adenine, and guanine react slowly or not at all under SHJ conditions (although their N-acetylated derivatives react more rapidly).
Silylation is most commonly accomplished using HMDS, which evolves ammonia as the only byproduct of silylation. Catalytic or stoichiometric amounts of acidic additives such as trimethylsilyl chloride accelerate silylation; when such an additive is used, ammonium salts will appear in the reaction as a turbid impurity.
Lewis acids should be distilled immediately before use for best results. More than about 1.2-1.4 equivalents of Lewis acid are rarely needed. Acetonitrile is the most common solvent employed for these reactions, although other polar solvents are also common. Workup of reactions employing TMSOTf involves treatment with an ice-cold solution of sodium bicarbonate and extraction of the resulting sodium salts. When tin(IV) chloride is used in 1,2-dichloroethane, workup involves the addition of pyridine and filtering of the resulting pyridine-tin complex, followed by extraction with aqueous sodium bicarbonate.