Application of a High-Throughput Enantiomeric Excess Optical Assay Involving a Dynamic Covalent Assembly: Parallel Asymmetric Allylation and Sensing of Homoallylic Alcohols.

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.