Expedited Aminoglutarimide C-N Cross-Coupling Enabled by High-Throughput Experimentation.

A simple protocol for the Buchwald-Hartwig cross-coupling of (hetero)aryl halides with unprotected aminoglutarimide to afford diverse cereblon binding motifs is disclosed. The development of this C-N cross-coupling method was enabled by high-throughput combinatory screening of solvents, bases, temperatures, and ligands. Scope studies revealed generality across various heteroaryl and aryl halides with the reaction proceeding under mild conditions.