Palladium/Norbornene-Cocatalyzed Ortho-Amination of Aryl Iodides: A Systematic Elucidation of the Mechanisms and Roles of Cs₂CO₃ Base via Computational and Mass Spectrometric Approaches

The Catellani-type palladium/norbornene-cocatalyzed ortho-amination of aryl halides has been widely applied.Although a Pd(0)/Pd(II)/Pd(IV)mechanism is generally adopted, some key issues remain to be addressed.Combined mass spectrometry (MS) and theoretical study have been carriedout, and the following observations and conclusions are obtained:(1) MS studies detected a Cs-containing Pd-IV complex (m/z = 752.0947) to confirm the existenceof Pd-IV intermediate; (2) density functional theory (DFT)calculations indicate that 2-iodotoluene is more reactive than morpholine-OBzin Pd-0(PPh3)(2) oxidative additionto form Pd-II intermediate; (3) for the Pd-II aryl-NBE-palladacycle(ANP) species, Cs2CO3 as a ligand coordinatesbetter than PPh3 by computation; (4) with the involvementof Cs2CO3, Pd-II oxidative additioninto morpholine-OBz to form a Pd-IV intermediatebecomes favored over Pd-II oxidative addition into 2-iodotolueneand C(sp(2))-C(sp(3)) reductive elimination;and (5) the base effects of Cs2CO3 and K2CO3 are also compared, which are in agreement withthe experimental findings that the latter results in a much loweryield.