Palladium-Catalyzed C–N Cross-Coupling of NH-Heteroarenes and Quaternary Ammonium Salts via C–N Bond Cleavage

Abstract

In this paper, we extend the substrate class of Buchwald−Hartwig amination to quaternary ammonium salts. In the presence of Pd(OAc) 2 and t-BuXPhos, the coupling of aryl-or arylmethyltrimethylammonium triflates with NH-heteroarenes via C−N bond cleavage affords the desired N-aryl or N-arylmethyl heteroarenes in moderate to excellent yields.

Recent Progress Concerning the N-Arylation of Indoles

“…In some cases, the palladium-catalyzed reaction of quaternary ammonium salts with indoles in the presence of potassium tert -butoxide can be used to prepare N -arylated indoles, although the reported scope of the reaction is limited to the preparation of four simple N -arylindoles, S15-4 . However, the synthesis of N -alkylated indoles by means of this approach is convenient [ 70 ]. Additionally, tosylates are sufficiently reactive for the preparation of N -arylindoles.…”

Trialkylammonium salt degradation: implications for methylation and cross-coupling

“…19, see Experimental ESI Section 20 † for optimisation). A range of substituents and structural complexities around the phenol ring were tolerated in these methylation reactions, and most with good to excellent isolated yields (17,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)34). Additionally, thiophenol and benzoic acid could be methylated under the applied conditions to give thioether 32 and ester 33 with good 77% and 80% yields, respectively.…”

“…Applications and divergent reactivity of trialkylammonium salts Trialkylammonium (specically N,N,N-trimethylanilinium) salts have found wide-ranging applications in synthesis, spanning phase-transfer catalysis, 1 supramolecular ion-pairing catalysis, 2,3 host-guest binding studies, 4 O-methylation, 5 O-arylation, 6 heteroatom arylations, 7 C-H methylation, 8 C-arylation, [9][10][11] uorine radiolabeling, [12][13][14][15] organometallic ligand design, [16][17][18][19][20][21] antimicrobial polymer design, 22 arene reduction, 23 pH sensing, 24 and a range of metal-catalysed cross-coupling methodologies. [25][26][27][28][29][30][31][32] The dichotomy of arylation versus methylation reactivity, while important for optimising the above-listed applications, is rarely studied in detail. Understanding the dual reactivity of N,N,N-trimethylanilinium salts thus serves as the focus of our study.…”

A Mechanistic Analysis of Trimethylanilinium Salt Degradation: Implications for Methylation and Cross-coupling Applications

“…We next investigated the ability of 11a to methylate a range of phenols and related nucleophiles under our applied reaction conditions (Figure 19, see Experimental Supporting Information Section 20 for optimisation). A range of substituents and structural complexities around the phenol ring were tolerated in these methylation reactions, and most with good to excellent yields (17,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)34). Additionally, thiophenol and benzoic acid could be methylated under the applied conditions to give thioether 32 and ester 33 with good 77% and 80% yields, respectively.…”