Ana L. Aguirre, Amanda W. Dombrowski, Noah P. Tu, Shubhendu S. Karandikar, Ying Wang

The Journal of Organic Chemistry 

DOI:  10.1021/acs.joc.6c00134

Abstract

In this work, we present the creation and implementation of a ChemBead-enabled, on-DNA high-throughput experimentation (HTE) platform to identify more general and mild reaction conditions for challenging C–N couplings. The platform was developed by adapting our small-molecule system to address the inherent challenges of on-DNA chemistry. The results generated by the platform were compared to the standard operating procedure for DNA-encoded library (DEL) production to ensure the translation of any promising conditions. The platform was used to discover a condition that has not been previously reported for on-DNA C–N coupling. This condition is best suited for secondary amines and select primary amines on short DNA substrates; primary aliphatic amines on elongated DNA-tagged aryl halide conjugates remain a challenge. This newly identified condition can be applied to DNA-encoded library constructions