Effects of Bases and Halides on the Amination of Chloroarenes Catalyzed by Pd(PtBu₃)₂

Abstract

We report a detailed study of the effects of anions on the rates of the amination of aryl halides catalyzed by palladium complexes of the hindered alkylmonophosphine PBu. These reactions occur by turnover-limiting oxidative addition. The extent of the dependence of the rates on the concentration and identity of bases was found to depend on the electronic properties of the haloarenes. The rates of reactions of electron-rich and electron-neutral chloroarenes were independent of the concentration of the bulky alkoxide base OCEt, but they were dependent on the concentrations of the less hindered OBu and the softer 2,4,6-tri--butylphenoxide bases. The reactions were fastest when 2,4,6-tri--butylphenoxide was used as base and slowest when NaOCEt was used as base. A concurrent reaction pathway involving simultaneous oxidative addition of chloroarenes to [Pd(PBu)] and [(PBu)Pd(OR)] may explain the dependence of the rates of reactions of electron-rich and electron-neutral chloroarenes on the identity and concentration of bases. The rates of reactions of electron-poor chloroarenes and the reactions of bromoarenes were of the concentration of OCEt, OBu, or 2,4,6-tri--butylphenoxide bases but were on the identity of bases, even though an adduct of the base did not accumulate in any observable amounts. Further, long induction periods were observed for the reactions of electron-poor chloroarenes. These long induction periods suggest that the complex kinetic behavior could result from the generation of several catalytically active species.

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

“…For example, Hartwig has shown that the presence of nucleophilic alkoxides [25] and amines, which form complexes with various intermediates of the catalytic cycle (Scheme 1), leads to alternative catalytic cycle pathways. The nature of the spectator ligand (NHC vs phosphine) additionally complicates the picture.…”

“…In our study, the difference of yields observed upon change of base points to the deprotonation of the Pd-bound amine being the most likely rate-determining step of the process. Compared to the extensive mechanistic and computational studies [25,26] with phosphine ligands conducted by the groups of Buchwald and Hartwig, there is a single DFT computational paper on the Buchwald-Hartwig arylation with carbene ligands. [27] Significantly, this work does not include calculations of the crucial deprotonation of the Pd-bound amine step.…”

Dialkylbiaryl phosphines in Pd-catalyzed amination: a user's guide

“…140 Unfortunately, it is not possible to select the base purely on the grounds of the p K a of the free N nucleophile as the p K a is changed significantly by binding to Pd, which typically occurs before deprotonation (Scheme 1). Furthermore, inorganic bases such as Cs 2 CO 3 can act heterogeneously in non-polar solvents where they can behave as much stronger bases than might be predicted from their solution phase p K a value.…”

Amination with Pd–NHC Complexes: Rate and Computational Studies on the Effects of the Oxidative Addition Partner

“…Further, KOtBu, a relatively strong base, promoted good levels of amination seemingly irrespective of the electronic structure of the aryl halide. [6] This illustrates that amine coordination and deprotonation are not unrelated events. Under mildly basic conditions, strong amine coordination to the metal is necessary to lower the pK a of the metal ammonium salt enough to allow deprotonation to take place.…”