Jo H H, Gao X, You L, Anslyn E V, Krische M J
Department of Chemistry, The University of Texas at Austin, Austin, Texas, 78712.
Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, P.R. China.
Chem Sci. 2015 Dec;6(12):6747-6753. doi: 10.1039/C5SC02416A. Epub 2015 Jul 13.
Asymmetric Ir-catalyzed C-C coupling of primary alcohols with allyl-acetates, as described by Krische, to form chiral secondary homo-allylic alcohols were performed in parallel as a means to optimize the values thereof. Specifically, approximately 400 examples of this reaction were performed by varying the catalyst, added acids and bases, and starting reactants, to form 4-phenyl-1-butene-4-ol (). The values for the transformations were determined in a high-throughput fashion using a 4-component assembly that creates a circular dichroism signal indicative of the extent of asymmetric induction. Further, a parallel and rapid quantitative TLC method measures the yield of each reaction, revealing which reactions give reliable values in the CD-based assay. Overall, the nearly 200 reactions whose values were determined could be quantitated in under two hours. Using a combination of the TLC method to measure yield with the CD-assay to measure values, several trends in reaction conditions were revealed. For example, it was found that the cyclometallated iridium catalyst modified by BINAP and -nitro--cyano-benzoic acid delivered adduct with the highest levels of enantiomeric enrichment (94%), whereas the corresponding SEGPHOS-modified catalyst gave a comparable yield but lower (91%). Most importantly, this study shows that supramolecular assemblies can report hundreds of values in a rapid and reliable fashion to analyze parallel synthesis routines.
如克里施所描述的，伯醇与乙酸烯丙酯的不对称铱催化碳 - 碳偶联反应，用于生成手性仲高烯丙醇，该反应以平行方式进行，作为优化其对映体过量值的一种手段。具体而言，通过改变催化剂、添加的酸和碱以及起始反应物，进行了约400个该反应的实例，以生成4 - 苯基 - 1 - 丁烯 - 4 - 醇。使用一种四组分组件以高通量方式确定转化反应的对映体过量值，该组件会产生一个圆二色性信号，该信号指示不对称诱导的程度。此外，一种平行且快速的定量薄层色谱法可测量每个反应的产率，从而揭示哪些反应在基于圆二色性的分析中能给出可靠的对映体过量值。总体而言，近200个已确定对映体过量值的反应能够在两小时内完成定量分析。通过结合使用薄层色谱法测量产率和圆二色性分析来测量对映体过量值，揭示了反应条件中的几个趋势。例如，发现由联萘二苯基膦（BINAP）和对硝基苯甲腈修饰的环金属化铱催化剂得到的加合物具有最高水平的对映体富集（94%），而相应的由双亚膦配体（SEGPHOS）修饰的催化剂产率相当，但对映体过量值较低（91%）。最重要的是，这项研究表明超分子组件能够以快速且可靠的方式报告数百个对映体过量值，以分析平行合成程序。
