Syntheses of Pyrroles, Pyridines, and Ketonitriles via Catalytic Carbopalladation of Dinitriles

Abstract

The first example of the Pd-catalyzed addition of organoboron reagents to dinitriles, as an efficient means of preparing 2,5-diarylpyrroles and 2,6-diarylpyridines, has been discussed here. Furthermore, the highly selective carbopalladation of dinitriles with organoboron reagents to give long-chain ketonitriles has been developed as well. Based on the broad scope of substrates, excellent functional group tolerance, and use of commercially available substrates, the Pd-catalyzed addition reaction of arylboronic acid and dinitriles is expected to be significant in future synthetic procedures.

Organocatalytic Decarboxylation and Dual C(sp3)−H Bond Functionalization Toward Facile Access to Divergent 2,6‐Diarylpyridines

“…Interestingly, the yield of 3 aa was further increased to 78% with 20 mol% catalyst loading (entry 12). In continuation, we have studied the effect of temperature and reaction time for the conversion of 1 a and 2 a to the desired product 3 aa (entries [14][15][16][17]. To our dismay, unsatisfactory results were obtained on altering reaction parameters in terms of temperature and time.…”

“…2,6‐Bis(4‐bromorophenyl)pyridine ( 3 qa ) [17] : White solid , R f =0.65 (SiO 2 , Hexane/EtOAc=9 : 1); purification system : Column chromatography (SiO 2 , 100–200 mesh) (Hexane/EtOAc=98 : 2); yield : 125 mg (65%); m.p =158–160 °C (Lit [17] 157–160 °C); 1 H NMR (400 MHz, CDCl 3 ): δ=8.07 (dd, J =8.0 Hz, 4H; 8‐H), 7.85 (t, J =8.0 Hz, 1H; 4‐H), 7.70 (d, J =8.0 Hz, 2H; 3‐H and 5‐H), 7.65 (dd, J =8.0 Hz, 4H; 9‐H) ppm; 13 C NMR (100 MHz, CDCl 3 ) δ=155.8 (C‐2 and C‐6), 138.1 (C‐4), 137.7 (C‐7), 131.8 (C‐9), 128.5 (C‐8), 123.5 (C‐10), 118.6 (C‐3 and C‐5) ppm; HRMS (EI‐QTOF , [M+H] + ): calculated for C 17 H 12 Br 2 N: 387.9336; found: 387.9330.…”

“…39-7.31 (m, 4H; 10-H and 11-H) 2,6-Bis(4-chlorophenyl)pyridine (3 na) [12m] : White solid, R f = 0.60 (SiO 2 , Hexane/EtOAc = 9 : 1); purification system: Column chromatography (SiO 2 , 100-200 mesh) (Hexane/EtOAc = 99 : 1); yield: 109 mg (73%); m.p = 159-161 °C (Lit [12m] 158-161 °C); 1 H NMR (600 MHz, CDCl 3 ): δ = 8.07 (dd, J = 8.8 Hz, 4H; 8-H), 7.82 (t, J = 7.8 Hz, 1H; 4-H), 7.67 (d, J = 7.7 Hz, 2H; 3-H and 5-H), 7.46 (d, J = 8.2 Hz, 4H; 9-H) ppm; 13 C NMR (150 MHz, CDCl 3 ) δ = 155.7 (C-2 and C-6), 137.7 (C-4), 137.6 (C-7), 135.2 (C-10), 128.8 (C-8), 128.2 (C-9), 118.6 (C-3 and C-5) ppm; HRMS (EI-QTOF, [M + H] + ): calculated for C 17 H 12 Cl 2 N: 300.0341; found: 300.0335. [12m] : Yellow solid, R f = 0.65 (SiO 2 , Hexane/EtOAc = 9 : 1); purification system: Column chromatography (SiO 2 , 100-200 mesh) (Hexane/EtOAc = 97 : 3); yield: 114 mg (59%); m.p = 132-134 °C (Lit [16] 134-137 °C); [11c] : Yellow oil, R f = 0.70 (SiO 2 , Hexane/EtOAc = 9 : 1); purification system: Column chromatography (SiO 2 , 100-200 mesh) (Hexane/EtOAc = 97 : 3); yield: 116 mg (60%); m.p = 35-37 °C (Lit [11c] 36-37 °C); 1 H NMR (400 MHz, CDCl 3 ): δ = 8.27 (t, J = 3.6 Hz, 2H; 8-H), 8.05 (dt, J = 7.8 Hz, 2H; 12-H), 7.84 (t, J = 6.8 Hz, 1H; 4-H), 7.69 (d, J = 8.0 Hz, 2H; 3-H and 5-H), 7.57 (ddd, J = 8.0 Hz, 2H; 10-H and 10-H), 7.37 (t, J = 6.8 Hz, 2H; 11-H) ppm; 13 2,6-Bis(4-bromorophenyl)pyridine (3 qa) [17] : White solid, R f = 0.65 (SiO 2 , Hexane/EtOAc = 9 : 1); purification system: Column chromatography (SiO 2 , 100-200 mesh) (Hexane/EtOAc = 98 : 2); yield: 125 mg (65%); m.p = 158-160 °C (Lit [17] 157-160 °C); -11), 131.75, 128.55 (q, J = 30.0 Hz, C-8), 128.49 (C-10), 126.4 (q, J = 5.0 Hz, C-9), 124.3 (q, J = 272.0 Hz, C-13), 122.9 (C-12), 120.2 (C-3 and C-5) ppm; HRMS (EI-QTOF, [M + H] + ): calculated for C 19 H 12 F 6 N: 368.0873; found: 368.08710. [12m] : Pale yellow solid, R f = 0.65 (SiO 2 , Hexane/EtOAc = 9 : 1); purification system: Column chromatography (SiO 2 , 100-200 mesh) (Hexane/EtOAc = 99 : 1); yield: 127 mg (69%); m.p = 143-144 °C (Lit [12m] 144-146 °C); Dimethyl 4,4'-(pyridine-2,6-diyl)dibenzoate (3 ua) [18] [19] : Pale white solid, R f = 0.62 (SiO 2 , Hexane/EtOAc = 9 : 1); purification system: Column chromatography (SiO 2 , 100-200 mesh) (Hexane/EtOAc = 100 : 0); yield: 84 mg (54%); m.p = 230-232 °C (Lit [19] 233-235 °C); 1 H NMR (500 MHz, CDCl 3 ): δ = 7.90-7.84 (m, 3H; 3-H, 4-H and 5-H), 7.68 (t, [3,2':6',3'']-Terpyridine (3 xa) [20] : White solid, R f = 0.60 (SiO 2 , Hexane/EtOAc = 2 : 8); purification system: Column chromatography (SiO 2 , 100-200 mesh) (Hexane/EtOAc = 98 : 2); yield: 68 mg (58%); 3,5-Dimethyl-2,6-diphenylpyridine (3 ya) [12m] : Pale yellow solid, R f = 0.70 (SiO 2 , Hexane/EtOAc = 9 : 1); purification system: Column chromatography (SiO 2 , 100-200 mesh) (Hexane/EtOAc = 99 : 1); yield: 83 mg (64%); m.p = 127-129 °C (Lit…”

Palladium(II)-Catalyzed C(sp)–C(sp2) Coupling: A Direct Approach to Multi-Substituted Pyrrolo[1,2-a]pyrazines

“…SYNTHESIS0 0 3 9 -7 8 8 1 1 4 3 7 -2 1 0 X Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart 2021, 53, 2051-2056 Palladium-catalyzed synthesis of arylketones through addition of arylboronic acids to nitriles was initially developed by Lacrock's group, 15,16 and it has been exploited in novel synthetic strategies to provide functionalized heterocycles in recent years. [17][18][19][20][21] Based on our previous work, 22,23 we envisioned that 2-formylpyrroloacetonitriles might afford pyrrolo [1,2-a]pyrazine nucleus through C-C coupling with phenylboronic acid and further intramolecular cyclization. Herein, we report a novel Pd-catalyzed tandem reaction to deliver pyrrolo [1,2-a]pyrazines with easy manipulation.…”

A magnetic porous organic polymer: catalytic application in the synthesis of hybrid pyridines with indole, triazole and sulfonamide moieties

“…Pyridine scaffolds as the privileged heterocyclic nucleus have been found in many natural products, pharmaceutical active molecules, organic synthesis, supramolecular chemistry, functional materials, agricultural applications, coordination chemistry and catalytic systems. [19][20][21][22][23] These special systems have a vital role in biologically active natural substances such as nicotine, vitamin B6 and oxido-reductive NADP-NADPH coenzymes. 24,25 The irreplaceable properties of pyridine families as HIV protease inhibitor, 26 anticancer, 27 acetylcholinesterase inhibitor, 24 anti-inammatory, 28 antihypertensive 29 and antidepressant 30 can be a persuasive reason for the synthesis of a new series of these compounds.…”