Mechanistic Aspects of Pincer Nickel(II)-Catalyzed C–H Bond Alkylation of Azoles with Alkyl Halides

Abstract

The quinolinyl-based pincer nickel complex, κN,κN,κN-{C9H6N-(μ-N)-C6H4–NMe2}­NiCl [(QNNNMe2)­NiCl; (1)] has recently been demonstrated to be an efficient and robust catalyst for the alkylation of azoles with alkyl halides under copper-free conditions. Herein, we report the detailed mechanistic investigation for the alkylation of azoles catalyzed by (QNNNMe2)­NiCl (1), which highlights an iodine-atom transfer (IAT) mechanism for the reaction involving a NiII/NiIII process. Deuterium labeling experiments indicate reversible cleavage of the benzothiazole C–H bond, and kinetic studies underline a fractional negative rate order with the substrate benzothiazole. The involvement of an alkyl radical during the alkylation is validated by radical clock and external additive experiments. An active intermediate species (QNNNMe2)­Ni­(benzothiazolyl) (5a) has been isolated and structurally characterized. The complex (QNNNMe2)­Ni­(benzothiazolyl) (5a) is found to be the resting state of catalyst 1. Kinetic analysis of electronically different intermediates suggests that the step involving the reaction of 5a with alkyl iodide is crucial and a rate-influencing step. DFT calculations strongly support the experimental findings and corroborate an IAT process for the alkylation reaction.

Benzothiazole Nickelation: An Obstacle to the Catalytic Arylation of Azoles by Cyclopentadienyl Nickel N-Heterocyclic Carbene Complexes

“…The Cp and IMes protons are found at values that are typical for NiCp(IMes) compounds [27][28][29][30][31][32][33][35][36][37]. Regarding the 13 C{ 1 H} NMR spectrum, the C(2) carbon of the benzothiazolyl moiety is observed at 176.0 ppm, which is significantly downfield compared to the corresponding carbon of free benzothiazole (153.8 ppm) [42], and thus confirms its metallation ( Figure S5) [23]. In addition, it is worth mentioning that the carbene carbon signal of 7 is downfield shifted (177.9 ppm) when compared to that of 3 (165.9 ppm [35]), which suggests a decrease in the Lewis acid character of the metallic center caused by an increase in the σ-donor ability of the ancillary ligand, [43][44][45][46].…”

“…Thus, although it obviously constitutes a potential energy well, complex 7 is an interesting example of azolyl trapping in such (attempted) direct coupling. Furthermore, it is to our knowledge only the second C(2)-benzothiazolyl-nickel species reported to date [23].…”

“…Complex 7 was also observed in the attempted couplings with the cationic complex 6 ( Figure S3), highlighting a general behaviour for these CpNi(NHC) species thereof. Interestingly, although C(2)-benzoxazolyl or benzothiazolyl complexes are often proposed as intermediates in C-H/C-X couplings between heteroarenes and aryl, alkenyl or alkyl electrophiles [5,10,12,14,16,17,19,20,22,23], they remain very rare. We are indeed aware of only four related PCN-Pd [39][40][41] and NNN-Ni [23] pincer species, which have been isolated with a benzothiazolyl ligand and demonstrated to be intermediates in similar couplings.…”

“…Thus, although it obviously constitutes a potential energy well, complex 7 is an interesting example of azolyl trapping in such (attempted) direct coupling. Furthermore, it is to our knowledge only the second C(2)-benzothiazolyl-nickel species reported to date [23]. Interestingly, although C(2)-benzoxazolyl or benzothiazolyl complexes are often proposed as intermediates in C-H/C-X couplings between heteroarenes and aryl, alkenyl or alkyl electrophiles [5,10,12,14,16,17,19,20,22,23], they remain very rare.…”

“…The recent trend to use 3d transition metal catalysts, that is driven by economic and environmental concerns, has led to a re-assessment of nickel's reactivity [1][2][3][4]. In particular, nickel catalysts have emerged as promising candidates for C-H bond functionalization [5][6][7][8], and nickel-catalyzed reactions between (hetero)arenes and aryl halides [9][10][11][12], phenol derivatives [13][14][15][16][17][18], aryl or alkenyl esters [19][20][21] or even alkyl halides [22,23] have been shown to be reliable atom-economical alternatives to palladium-catalyzed cross-couplings. In this context, we have recently reported that the unsaturated T-shaped nickelacycle 1, that bears a mono-anionic C,C-NHC-cyanoalkyl chelate (NHC = N-heterocyclic carbene), shows moderate activity for the coupling of benzothiazole with aryl iodides (Scheme 1) [24].…”