Accelerated Asymmetric Reaction Screening with Optical Assays

In memory of Rachel Aterrado who is sorely missed in our department.

Abstract

Asymmetric 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 Introduction

2 Fluorescence Assays

3 UV Sensing Methods

4 Sensing with Circular Dichroism Probes

5 Hybrid Approaches

6 Optical Analysis with Intrinsically CD-Active Reaction Products

7 Conclusion

Key words

asymmetric synthesis - reaction development - optical methods - high-throughput screening - chirality sensing

Publication History

Received: 10 January 2022

Accepted after revision: 28 January 2022

Accepted Manuscript online:
28 January 2022

Article published online:
25 February 2022

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