Per(6-O-tert-butyldimethylsilyl)-α-, β- and γ-cyclodextrin derivatives are well-known as synthetic intermediates that enable the selective mono-, partial, or perfunctionalization of the secondary face of the macrocycles. Although silylation of the primary rim is readily achieved by treatment with tert-butyldimethylsilyl chloride in the presence of pyridine (either alone or mixed with a co-solvent), the reaction typically results in a mixture containing both under- and oversilylated byproducts that are difficult to remove. To address this challenge in preparing a pure product in high yield, we describe an approach that centers on the addition of a controlled excess of silylating agent to avoid the presence of undersilylated species, followed by the removal of oversilylated species by column chromatography elution with carefully designed solvent mixtures. This methodology works well for 6-, 7-, and 8-member rings (α-, β-, and γ-cyclodextrins, respectively) and has enabled us to repeatedly prepare up to ⁓35 g of ≥98% pure product (as determined by HPLC) in 3 d. We also provide procedures for lower-scale reactions, as well as an example of how the β-cyclodextrin derivative can be used for functionalization of the secondary face of the molecule.

全（6 - O-叔丁基二甲基甲硅烷基）-α-、β- 和 γ-环糊精衍生物是众所周知的合成中间体，能够选择性地单官能化、部分官能化或全官能化大环的次级面。尽管初级边缘的甲硅烷基化很容易通过用tert处理来实现-丁基二甲基甲硅烷基氯在吡啶（单独或与助溶剂混合）的存在下，该反应通常会产生包含难以去除的甲硅烷基化不足和过度甲硅烷基化的副产物的混合物。为了应对以高产率制备纯产品的这一挑战，我们描述了一种方法，该方法的核心是添加可控过量的甲硅烷基化剂以避免存在甲硅烷基化不足的物质，然后通过柱色谱洗脱小心去除甲硅烷基化过度的物质设计的溶剂混合物。这种方法适用于 6、7 和 8 元环（分别为 α-、β- 和 γ-环糊精），并使我们能够重复制备多达 ⁓35 g ≥98% 的纯产品（如通过 HPLC 测定）在 3 d 内。我们还提供小规模反应的程序，