An efficient approach to synthesis of previously unavailable 2-substituted difluorocyclobutane building blocks was developed and applied on a multigram scale. The key step of the synthetic sequence included deoxofluorination of O-protected 2-(hydroxylmethyl)cyclobutanone. Dissociation constants (pK_a) and log P values for 2,2-difluorocyclobutaneamine and 2,2-difluorocyclobutanecarboxylic acid or their derivatives were measured and compared with the values obtained for the corresponding 3,3-difluorocyclobutane derivatives and nonfluorinated counterparts. Three-dimensional structures of 2,2- and 3,3-difluorocyclobutanamines were compared using exit vector plot analysis of X-ray crystallographic data.

中文翻译：

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宝石的最后部分-二氟环烷烃：2,2-二氟环丁基取代的构建基的合成和表征

开发了一种有效的合成先前无法获得的2-取代的二氟环丁烷结构单元的方法，并已应用于多克规模。合成序列的关键步骤包括O保护的2-（羟甲基）环丁酮的脱氧氟化作用。测量了2，2-二氟环丁烷胺和2，2-二氟环丁烷羧酸或其衍生物的解离常数（p K _a）和log  P值，并将其与相应的3，3-二氟环丁烷衍生物和非氟化对应物所获得的值进行比较。使用X射线晶体学数据的出口向量图分析比较了2,2-和3,3-二氟环丁胺的三维结构。