Mechanistic Insights into Pincer-Ligated Palladium-Catalyzed Arylation of Azoles with Aryl Iodides: Evidence of a Pd^II–Pd^IV–Pd^II Pathway

Abstract

Pincer-based ( R2 POCN R ′ 2 )PdCl complexes along with CuI cocatalyst catalyze the arylation of azoles with aryl iodides to give the 2-arylated azole products. Herein, we report an extensive mechanistic investigation for the direct arylation of azoles involving a well-defined and highly efficient ( iPr2 POCN Et2 )PdCl (2a) catalyst, which emphasizes a rare Pd II −Pd IV −Pd II redox catalytic pathway. Kinetic studies and deuterium labeling experiments indicate that the C−H bond cleavage on azoles occurs via two distinct routes in a reversible manner. Controlled reactivity of the catalyst 2a underlines the iodo derivative ( iPr2 POCN Et2 )PdI (3a) to be the resting state of the catalyst. The intermediate species ( iPr2 POCN Et2 )Pd-benzothiazolyl (4a) has been isolated and structurally characterized. A determination of reaction rates of compound 4a with electronically different aryl iodides has revealed the kinetic significance of the oxidative addition of the C(sp 2 )−X electrophile, aryl iodide, to complex 4a. Furthermore, the reactivity behavior of 4a suggests that the arylation of benzothiazole proceeds via an oxidative addition/ reductive elimination pathway involving a ( iPr2 POCN Et2 )Pd IV (benzothiazolyl)(Ar)I species, which is strongly supported by DFT calculations.

Improved Synthesis of Symmetrical 2,5-Diarylimidazoles by One-Pot Palladium-Catalyzed Direct Arylation Tailored on the Electronic Features of the Aryl Halide

“…Our results are in fact similar, for example, to those very recently reported for the direct arylation of azoles in the presence of a pincer-ligated palladium complex. 16 In that study, the high reactivity observed when electron-rich aryl halides are the coupling partners was attributed to a better stabilization of Pd(IV) intermediates resulting from the oxidative addition of the aryl halide to a Pd(II) species. a Method A: 1) 2 (1.0 mmol), 3 (3.0 equiv), Pd(OAc) 2 (5 mol%), CsOAc (2.0 equiv), DMA (5 mL), 110 °C, 24 h; 2) CuI (2.0 equiv), 140 °C, 24 h. Method B: (1.0 mmol), 3 (3.0 equiv), Pd(OAc) 2 (5 mol%), P(2-furyl) 3 (10 mol%), K 2 CO 3 (2.0 equiv), xylene (5 mL), 140 °C, 24 h. b Isolated yield.…”

“…Regarding electron-rich aryl bromides, the results using Method A were not completely satisfactory. The reaction of 4-bromotoluene (3l), 3-bromotoluene (3m), 2-bromotoluene (3n), and 4-bromoanisole (3o) gave the 2,5-diarylimidazoles 4l, 4m, 4n, and 4o, in 49%, 47%, 23%, and 33% isolated yield, respectively (Table 2, entries 12 and [14][15][16].…”

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

“…of iodobenzene in 1,4-dioxane at 140 • C for 16 h. The reaction led to a massive decomposition of the complex together with a small amount of the expected coupling product (<15% of the identified species) as inferred from the 1 H NMR analysis of the crude reaction mixture that shows a very complex mixture. This illustrates the less stable (or more reactive) character of the Cp* derivative 8, when compared to its Cp analogue 7, and suggests the possible involvement of such a benzothiazolyl complex in the coupling reaction [23,[39][40][41], provided that it does not constitute a potential energy well like the Cp derivative 7.…”

“…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.…”

Well‐Defined N‐Heterocyclic Carbene‐Palladium Complexes as Efficient Catalysts for Domino Sonogashira Coupling/Cyclization Reaction and C‐H bond Arylation of Benzothiazole

“…Surprisingly, PEPPSI themed palladium precatalysts for the arylation of benzothiazole unit with aryl halides were not reported till date, whereas the arylation of other heterocyclic compounds like imidazoles, 2‐substituted thiophene derivatives, and 1‐methylpyrrole‐2‐carboxaldehyde with aryl halides have been studied extensively 2n, p, 13. Furthermore, mechanistic details of palladium catalyzed arylation of benzothiazoles by Punji and co‐workers revealed the importance of σ‐donor ligands on palladium center, which will enhance the oxidative addition of aryl halide electrophiles and stabilized the Pd (IV) intermediate . Based on the above findings we have explored the catalytic activity of our palladium complexes (having strong σ‐donor ligands such as N‐heterocyclic carbene) for C‐H bond arylation of benzothiazole at low catalyst loading.…”