Sonogashira Cross-Coupling of Aryl Ammonium Salts by Selective C–N Activation Catalyzed by Air- and Moisture-Stable, Highly Active [Pd(NHC)(3-CF₃-An)Cl₂] (An = Aniline) Precatalysts

Abstract

We report the Sonogashira cross-coupling of aryl ammonium salts catalyzed by air- and moisture-stable [Pd­(NHC)­(3-CF3-An)­Cl2] (An = aniline). This highly active Pd­(II)–NHC complex features broad scope and excellent C–N activation selectivity in the challenging alkynylative cross-coupling of aryl ammonium salts. Full structural characterization and computational studies demonstrate the effect of pyridine to aniline replacement as highly effective stabilizing ancillary ligand in well-defined Pd­(II)–NHCs. Considering the high reactivity and the recent commercialization of [Pd­(NHC)­(3-CF3-An)­Cl2] (Millipore Sigma, no. 915165), this catalyst represents an attractive approach to the activation of C–N bonds of broad synthetic interest.

Recent Expedition inPd‐CatalyzedSonogashira Coupling and Related Processes†

“…A Sonogashira cross‐coupling involving C–N bond cleavage of aryl ammonium salts as an electrophilic coupling partner is described by Shi/Dang/Cao [ 67 ] and Lei/Ma/Liu/Szostak [ 68 ] using Pd‐NHC catalyst system (Scheme 11).…”

Synthesis and a combined experimental/theoretical structural study of a comprehensive set of Pd/NHC complexes witho-,m-, andp-halogen-substituted aryl groups (X = F, Cl, Br, CF3)

“…[1][2][3][4][5][6][7][8][9][10][11] Their main advantages include a tunable electron-transfer ability to metal centers, as well as the ability to control the electronic and steric effects for each specific task by changing the substituents at nitrogen atoms. [12][13][14][15][16][17] There are a large number of studies devoted to the variation of steric bulk and electronic parameters of M/NHC complexes. [18][19][20] However, despite many years of active application, there are still only a few achievements in the synthesis and study of Pd/NHC complexes with NHC cores bearing electron-withdrawing groups.…”

Suzuki–Miyaura Cross-Coupling of 2-Pyridyl Trimethylammonium Salts by N–C Activation Catalyzed by Air- and Moisture-Stable Pd–NHC Precatalysts: Application to the Discovery of Agrochemicals

“…In this context, we became interested to leverage the well-known C–H Chichibabin amination of pyridines with selective N–C bond activation of 2-pyridyl ammonium salts (Figure C). , We recognized that the recent progress in N–C bond activation may allow for unconventional bond disconnection of 2-aminopyridines , while providing an attractive orthogonal strategy to the 2-pyridyl problem. Herein, we report the development of the first Suzuki–Miyaura cross-coupling of 2-pyridyl ammonium salts by highly selective N–C activation.…”

“…Furthermore, the utility of the method to the discovery of potent agrochemicals is presented. In light of the broad application of 2-arylpyridines, − the commercial availability of Pd­(II)–NHC precatalysts, , the operational simplicity of the process, and the versatility of N–C activation methods, − we anticipate that this C–H/N–C bond activation strategy will find wide application in organic synthesis.…”