Application of a high-throughput enantiomeric excess optical assay involving a dynamic covalent assembly: parallel asymmetric allylation and ee sensing of homoallylic alcohols
| Autor: | Eric V. Anslyn, Lei You, Hyun Hwa Jo, Xin Gao, Michael J. Krische |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Circular dichroism
010405 organic chemistry Chemistry organic chemicals General Chemistry 010402 general chemistry 01 natural sciences Asymmetric induction Combinatorial chemistry 0104 chemical sciences Adduct Catalysis chemistry.chemical_compound Yield (chemistry) Organic chemistry Enantiomer Enantiomeric excess BINAP |
| Zdroj: | Chemical Science. 6:6747-6753 |
| ISSN: | 2041-6539 2041-6520 |
| DOI: | 10.1039/c5sc02416a |
| Popis: | 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 cyclometallated 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. |
| Databáze: | OpenAIRE |
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