Micellar compartmentalization enables 1,2-diamination of aryl dihalides and access to novel NHC/anionic scaffolds via in situ base generation in water

Abstract: Achieving selective and general 1,2-diamination of aryl dihalides remains a major unsolved challenge in cross-coupling chemistry due to catalyst deactivation by ligand-like diamine products, competitive mono-amination, and hydrodehalogenation. We report a novel micellar strategy that overcomes these limitations and enables efficient palladium-catalyzed 1,2-diamination under sustainable, low-energy conditions. Our key innovation is the in situ generation of NaOtBu from inexpensive NaOH and t-BuOH within micellar nanoreactors, eliminating the need for costly, moisture-sensitive alkoxide bases. The lipophilic NaOtBu forms selectively inside the hydrophobic PS-750-M micelle core, where catalysis occurs—preventing the resulting 1,2-diamine products from occupying catalytic sites and suppressing de-ligandation events. This compartmentalization also minimizes unproductive hydrodehalogenation and enables low catalyst loadings, reduced temperatures, with water as the reaction medium. The method delivers a broad range of 1,2-diamines, including heteroaryl substrates and diverse amines, providing otherwise difficult-to-access scaffolds for NHC and anionic ligand development. Overall, this work introduces a combination of micellar catalysis and in situ base activation that directly addresses long-standing mechanistic barriers in diamination chemistry and establishes a greener, scalable, and resource-efficient platform for C–N bond formation. This work will also shed light on how traces of organic solvents can adversely impact this transformation.