Accelerated Asymmetric Reaction Screening with Optical Assays

Abstract

AbstractAsymmetric reaction development often involves optimization of several mutually dependent parameters that affect the product yield and enantiomeric excess. Widely available high-throughput experimentation equipment and optical sensing assays can drastically streamline comprehensive optimization efforts and speed up the discovery process at reduced cost, workload, and waste production. A variety of chiroptical assays that utilize fluorescence, UV, and circular dichroism measurements to determine reaction yields and ee values are now available, enabling the screening of numerous small-scale reaction samples in parallel with multi-well plate technology. Many of these optical methods considerably shorten work-up protocols typically required for traditional asymmetric reaction analysis and some can be directly applied to crude mixtures thus eliminating cumbersome separation and purification steps altogether.1 Introduction2 Fluorescence Assays3 UV Sensing Methods4 Sensing with Circular Dichroism Probes5 Hybrid Approaches6 Optical Analysis with Intrinsically CD-Active Reaction Products7 Conclusion