Ze Dong, Xianfeng Li, Qiuyi Chen, Qiang Li, Zhongqi Shi, Yangfeng Li, Cai-Guang Yang, Gong Zhang, Yizhou Li

Organic Letters

DOI: 10.1021/acs.orglett.6c03572

Abstract

Arylhydrazones represent a privileged class of scaffolds with diverse biological activities that are widely utilized in medicinal chemistry. Here, we report a mild yet effective strategy for constructing arylhydrazones via the in situ generation of DNA-conjugated aryl diazonium intermediates, followed by subsequent coupling with a variety of active methylene compounds. This method features broad substrate scopes, good to excellent conversions for both DNA-conjugated arylamine and DNA-conjugated active methylene coupling partners, and good compatibility with the DNA-encoded library (DEL) workflow, significantly expanding the accessible chemical space for DEL-based drug discovery.