Dynamic covalent kinetic resolution

ABSTRACT

Implemented with the highly efficient concept of Dynamic Kinetic Resolution (DKR), dynamic covalent chemistry can be a useful strategy for the synthesis of enantioenriched compounds. This gives rise to dynamic covalent kinetic resolution (DCKR), a subset of DKR that over the last decades has emerged as increasingly fruitful, with many applications in asymmetric synthesis and catalysis. All DKR protocols are composed of two important parts: substrate racemization and asymmetric transformation, which can lead to yields of >50% with good enantiomeric excesses (ee) of the products. In DCKR systems, by utilizing reversible covalent reactions as the racemization strategy, the substrate enantiomers can be easily interconverted without the presence of any racemase or transition metal catalyst. Enzymes or other chiral catalysts can then be adopted for the resolution step, leading to products with high enantiopurities. This tutorial review focuses on the development of DCKR systems, based on different reversible reactions, and their applications in asymmetric synthesis.

KEYWORDS:

• Dynamic kinetic resolution
• dynamic covalent chemistry
• asymmetric synthesis
• organocatalysis
• enzymatic catalysis

Acknowledgments

We acknowledge financial support from Natural Science Foundation of Jiangsu Province (BK20180625, to YZ), National First-class Discipline Program of Light Industry Technology and Engineering (LITE2018-20, to YZ), and the National Institutes of Health (1R21AI140418, to OR).