Catalyst-Controlled Regiodivergent C–H Arylation Site of Fluorinated 2-Arylpyridine Derivatives: Application to Luminescent Iridium(III) Complexes

Abstract

Regiodivergent C-H bond arylation of fluorinated 2-aryl-pyridines and-quinolines has been developed. The use of Pd catalyst allows to functionalize the C-H bond of the aryl flanked by two fluorine atoms (most acidic position); while using Ru catalyst, the arylation takes place at the ortho heterocycle position. Both reaction conditions exhibit a good functional group tolerance. The synthetically useful selectivity observed with Pd catalyst was applied to design novel C^N ligands for the preparation of luminescent cationic iridium(III) complexes. The influence of the incorporated aryl group onto the fluorinated phenyl unit and the fluorine position patterns on the photophysical properties is described.

Switching the site-selectivity of C–H activation in aryl sulfonamides containing strongly coordinating N-heterocycles

“…1D). [28][29][30][31][32][33][34][35][36][37][38] Both N-heterocycles and sulfonamides are ubiquitous in biologically active molecules owing to their hydrogen bond forming abilities and favorable drug-like properties. [39][40][41][42][43] Considering their dual pharmacological effects, switching the selectivity of the C-H functionalization of aryl sulfonamides containing strongly coordinating N-heterocycles would be invaluable in the late-stage modication of potential drug molecules ( Fig.…”

Palladium−Ruthenium Catalyst Complementarity Strengthens Ortho‐Directed C−H Bond Arylation of 2‐Arylpyrazines

“…When 1 equivalent of ( n ‐Bu) 4 NBr was employed in this reaction, the desired arylated pyrazine 1 was obtained in 62 % yield. Next, we also investigated the reactivity of Ru(II) catalytic system toward the mono‐C−H bond arylation using 1.5 equivalents of 2,3‐diphenylpyrazine with 1 equivalent of 4‐bromobenzonitrile using our previous conditions for C−H bond arylation of 2‐arylpyridine derivatives, [14] namely 5 mol% [RuCl 2 ( p ‐cymene] 2 associated with KOAc as the base in NMP at 150 °C (Scheme 1, middle). These phosphine‐free ruthenium conditions afforded the desired product 1 in 48 % yield without the formation of di‐ or multi‐arylated products.…”

“…2, 152.8, 150.5, 146.4, 142.9, 142.3, 138.0, 137.5, 135.1, 133.3, 131.5, 130.2, 129.6, 129.4, 129.0, 128.8, 128.7, 128.5, 127.8, 127.6, 126.6. MS (EI, 70 eV) m/z (%): 103 (14), 255 43) 359 (100[M] + . -2-yl)-[1,1'-biphenyl]-4-carbonitrile (12): Following general Procedure B using 2-phenylpyrazine (234 mg, 1.5 mmol) and 4bromobenzonitrile (182 mg, 1 mmol), the residue was purified by flash chromatography on aluminium oxide (Heptane-EtOAc, 90-10) to afford the desired compound 12 (182 mg, 71 %) as a pale yellow solid (Mp = 142-144°C): 1 H NMR (400 MHz, CDCl 3 ) δ 8.54 (s, 1H), 8.41 (d, J = 2.3 Hz, 1H), 8.24 (s, 1H), 7.71 (dd, J = 5.6, 3.4 Hz, 1H), 7.60-7.52 (m, 4H), 7.45 (dd, J = 5.6, 3.4 Hz, 1H), 7.24 (d, J = 8.2 Hz, 2H).…”

Effective Tools for the Metal‐Catalyzed Regiodivergent Direct Arylations of (Hetero)arenes

“…In 2019, we reported the regiodivergent C−H bond arylation of polyfluorinated 2‐arylpyridines and 2‐arylquinolines (Scheme 19). [38a] The use of a palladium catalyst promoted the functionalization of the C−H bond of the aryl flanked by two fluorine atoms which is the most acidic position (Scheme 20, a). The best results were obtained with PdCl(C 3 H 5 )(dppb) catalyst.…”