Conformationally Biased Selective Alkylation oftrans-Cyclohexane-1,2-bis(sulfonamide) Assisted by Solvent-Tuned Protecting Groups: Applications to the Synthesis of a Large Optically Active Polyazamacrocycle
作者:Carmen Peña、Ignacio Alfonso、Vicente Gotor
DOI:10.1002/ejoc.200600234
日期:2006.9
The selective alkylation of (R,R)-cyclohexane-1,2-bis(sulfonamide) with trityl bromoalkyl ethers has been studied in detail. The major formation of either mono- or dialkylated compounds clearly depends on the right combination of protecting groups and the reaction solvent. An exhaustive study suggests that this effect can be reasonably explained by the conformational preferences of the monoalkylated
已经详细研究了 (R,R)-环己烷-1,2-双(磺酰胺) 与三苯甲基溴烷基醚的选择性烷基化。单烷基化化合物或二烷基化化合物的主要形成显然取决于保护基团和反应溶剂的正确组合。一项详尽的研究表明,这种影响可以通过单烷基化化合物的构象偏好来合理解释,这也取决于反应介质、疏溶剂效应和弱分子内相互作用。通过 NOE 测量进行的结构分析表明,所有测试实例的溶液中都存在折叠构象。Monte Carlo 构象搜索支持该提议,显示折叠物种的分数与对单烷基化的选择性之间具有非常好的相关性。最后,调整反应条件,导致单烷基化合成中间体的延伸或折叠构象,被用于有效合成大型旋光多氮杂大环。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)