Scalable Transition-Metal-Free Synthesis of Aryl Amines from Aryl Chlorides through X@RONa-Catalyzed Benzyne Formation.

Aryl amines are highly useful organic chemicals, but large-scale, transition-metal-free syntheses of aryl amines are surprisingly underdeveloped. A mild and scalable (up to 500 mmol) aryl amine synthesis from benzyne chemistry was invented using easily accessible aryl chlorides as precursors, NaH as a stoichiometric base, and a new type of sodium alkoxide cluster, , as a catalyst. The cluster catalyst featured an externally hydrophobic dodecameric sodium alkoxide shell housing an encapsulated center anion. The cluster made from methoxy--butanol was found to be the most effective. The intramolecular version of this reaction allowed the synthesis of indolines and indoles. Experimental and computational mechanistic studies revealed that the rate-determining step was likely the transport of solid NaH into the cluster in the organic phase.