Application of a High-Throughput Enantiomeric Excess Optical Assay Involving a Dynamic Covalent Assembly: Parallel Asymmetric Allylation and Ee Sensing of Homoallylic Alcohols.
Application of a High-Throughput Enantiomeric Excess Optical Assay Involving a Dynamic Covalent Assembly: Parallel Asymmetric Allylation and Ee Sensing of Homoallylic Alcohols.
复制标题
DOI：
10.1039/c5sc02416a
复制
发表时间：
2015-12
期刊：
影响因子：
8.4
通讯作者：
Krische MJ
中科院分区：
文献类型：
--
作者：
Jo HH;Gao X;You L;Anslyn EV;Krische MJ
平行合成和高通量ee筛选。按照Krische的描述，平行进行了ir催化的伯醇与烯丙酸酯的不对称C-C偶联，形成手性仲均烯丙醇，以优化其ee值。具体来说，通过改变催化剂，添加酸和碱以及起始反应物，进行了大约400次反应，以形成4-苯基-1-丁烯-4-醇(1)。转换的ee值以高通量方式确定，使用4组分组件，该组件创建圆形二色信号，指示不对称诱导的程度。此外，平行和快速的定量TLC方法测量每个反应的产率，揭示哪些反应在基于cd的分析中给出可靠的ee值。总的来说，测定了近200个ee值的反应可以在两小时内定量。将薄层色谱法测定产率与CD-assay测定ee值相结合，揭示了反应条件的几个变化趋势。例如，发现由BINAP和间硝基-对氰基苯甲酸修饰的环金属化铱催化剂的加合物1的对映体富集水平最高（94%），而相应的segphos修饰催化剂的产率相当，但ee较低（91%）。最重要的是，这项研究表明，超分子组装可以快速可靠地报告数百个ee值，以分析平行合成程序。
Parallel synthesis and high-throughput ee screening. 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 ee 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 (1). The ee 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 ee values in the CD-based assay. Overall, the nearly 200 reactions whose ee 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 ee values, several trends in reaction conditions were revealed. For example, it was found that the cyclometalated iridium catalyst modified by BINAP and m-nitro-p-cyano-benzoic acid delivered adduct 1 with the highest levels of enantiomeric enrichment (94%), whereas the corresponding SEGPHOS-modified catalyst gave a comparable yield but lower ee (91%). Most importantly, this study shows that supramolecular assemblies can report hundreds of ee values in a rapid and reliable fashion to analyze parallel synthesis routines.