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Palladium/Norbornene-Cocatalyzed <i>Ortho</i>-Amination of Aryl Iodides: A Systematic Elucidation of the Mechanisms and Roles of Cs<sub>2</sub>CO<sub>3</sub> Base via Computational and Mass Spectrometric Approaches

Linxing Zhang, Ping Chen, Xuepeng Zhang, Xuepeng Zhang, Chengxi Yang, Tian‐Yu Sun, Xinhao Zhang, Xinhao Zhang, Yun‐Dong Wu

2023ACS Catalysis13 citationsDOI

Abstract

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 carried out, 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 existence of Pd IV intermediate; (2) density functional theory (DFT) calculations indicate that 2-iodotoluene is more reactive than morpholine–OBz in Pd 0 (PPh 3 ) 2 oxidative addition to form Pd II intermediate; (3) for the Pd II aryl-NBE-palladacycle (ANP) species, Cs 2 CO 3 as a ligand coordinates better than PPh 3 by computation; (4) with the involvement of Cs 2 CO 3, Pd II oxidative addition into morpholine–OBz to form a Pd IV intermediate becomes favored over Pd II oxidative addition into 2-iodotoluene and C(sp 2 )–C(sp 3 ) reductive elimination; and (5) the base effects of Cs 2 CO 3 and K 2 CO 3 are also compared, which are in agreement with the experimental findings that the latter results in a much lower yield.

Topics & Concepts

MorpholineChemistryArylPalladiumAminationReductive eliminationOxidative additionDensity functional theoryMedicinal chemistryLigand (biochemistry)Computational chemistryCatalysisNorborneneCombinatorial chemistryStereochemistryOrganic chemistryPolymerizationAlkylBiochemistryPolymerReceptorCatalytic C–H Functionalization MethodsCatalytic Cross-Coupling ReactionsAsymmetric Hydrogenation and Catalysis