Reevaluation of the Mechanism of the Amination of Aryl Halides Catalyzed by BINAP-Ligated Palladium Complexes

Abstract

Two previous mechanistic studies of the amination of aryl halides catalyzed by palladium complexes of 1,1'-binaphthalene-2,2'-diylbis(diphenylphosphine) (BINAP) are reexamined by the authors of both studies. This current work includes a detailed study of the identity of the BINAP-ligated palladium complexes present in reactions of amines with aryl halides and rate measurements of these catalytic reactions initiated with pure precatalysts and precatalysts generated in situ from [Pd2(dba)3] and BINAP. This work reveals errors in both previous studies, and we describe our current state of understanding of the mechanism of this synthetically important transformation. 31P NMR spectroscopy shows that several palladium(0) species are present in the catalytic system when the catalyst is generated in situ from [Pd2(dba)3] and BINAP, and that at least two of these complexes generate catalytic intermediates. Further, these spectroscopic studies and accompanying kinetic data demonstrate that an apparent positive order in the concentration of amine during reactions of secondary amines is best attributed to catalyst decomposition. Kinetic studies with isolated precatalysts show that the rates of the catalytic reactions are independent of the identity and the concentration of amine, and studies with catalysts generated in situ show that the rates of these reactions are independent of the concentration of amine. Further, reactions catalyzed by [Pd(BINAP)2] with added BINAP are found to be first-order in bromoarene and inverse first-order in ligand, in contrast to previous work indicating zero-order kinetics in both. These data, as well as a correlation between the decay of bromobenzene in the catalytic reaction and the predicted decay of bromobenzene from rate constants of studies on stoichiometric oxidative addition, are consistent with a catalytic process in which oxidative addition of the bromoarene occurs to [Pd(BINAP)] prior to coordination of amine and in which [Pd(BINAP)2], which generates [Pd(BINAP)] by dissociation of BINAP, lies off the cycle. By this mechanism, the amine and base react with [Pd(BINAP)(Ar)(Br)] to form an arylpalladium amido complex, and reductive elimination from this amido complex forms the arylamine.

Pd‐Catalyzed Aryl Amination Mediated by Well Defined, N‐Heterocyclic Carbene (NHC)–Pd Precatalysts, PEPPSI

“…Reactions carried out at room temperature were equally effective (entries 14 and 15). These results, in addition to earlier reports, [7] suggest that for effective amination a sterically demanding yet flexible environment in the vicinity of the metal center is essential.…”

“…Finally, reductive elimination yields the product concomitant with the regeneration of Pd 0 . [5,7] Keywords: amination · anilines · asymmetric catalysis · carbenes · palladium Abstract: Pd-N-heterocyclic carbene (NHC)-catalyzed Buchwald-Hartwig amination protocols mediated by Pd-PEPPSI precatalysts is described. These protocols provide access to a range of hindered and functionalized drug-like aryl amines in high yield with both electron-deficient and electron-rich aryl-and heteroaryl chlorides and bromides.…”

Amination with PdNHC Complexes: Rate and Computational Studies Involving Substituted Aniline Substrates

“…The deprotonation step (12 ! 13, as shown in Scheme 1 [13] ) is endothermic, with electron-withdrawing groups in both rings facilitating the reaction. Effects are calculated to be much more pronounced for substituents in the aniline (e.g., for the IPr derivative: CN 3.3, H 8.1, OMe 9.0 kcal mol…”

Biarylphosphanliganden in der palladiumkatalysierten Aminierung

“…Der Mechanismus der palladiumkatalysierten Aminierung war Gegenstand intensiver Untersuchungen mit zahlreichen Ligandensystemen (Schema 2). [109][110][111][112][113][114][115][116] [119] Dieser Effekt würde die Katalysatoraktivierung verzögern, da derartige Palladacyclen nur langsam in den aktiven Katalysator umgewandelt werden. [120] Dialkylbiarylphosphanliganden erhöhen die Katalysatorstabilität und die Elektronendichte am Metallzentrum ver-mutlich auch durch eine Wechselwirkung zwischen dem Palladiumatom und dem unteren Arenring des Liganden (siehe I).…”