Copper‐Catalyzed [2+2+1+1] Annulation for the Regioselective Synthesis of 2,6‐Diarylpyridines via C1‐Insertion and Subsequent Cyclization

Abstract

Copper‐catalyzed [2+2+1+1] annulation strategy has been investigated for the regioselective synthesis of symmetrical and unsymmetrical 2,6‐diarylpyridines using aliphatic amines as nitrogen source and DMSO as C1‐synthon. The developed protocol was successful for the transformation of non‐activated aromatic ketones and non‐activated aliphatic amines into 2,6‐diarylpyridines via an “easy to access” approach. This protocol has been verified on wide range of substrates having various functional groups.

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

“…With this much experimental evidence and literature precedence, [12m–o] we proposed an organocatalytic pathway towards the synthesis of 2,6‐diarylpyridines. To begin with, the reaction of acetophenone ( 1 a ) ([M] + =120.1) and glycine ( 2 a ) resulted in the formation of Schiff base A ([M+H] + =178.1).…”

“…Deuterated 2,6‐diphenylpyridine ( 3 aa‐ d ) [12o] : White solid , R f =0.7 (SiO 2 , Hexane/EtOAc=9 : 1); purification system : Column chromatography (SiO 2 , 100–200 mesh) (Hexane/EtOAc=99 : 1); yield : 76 mg (66%); 1 H NMR (400 MHz, CDCl 3 ): δ=8.08 (d, 4H; 8′‐H), 7.63 (s, 2H; 3′‐H and 5′‐H), 7.46–7.4 (m, 4H; 9′‐H), 7.37–7.34 (m, 2H; 10′‐H) ppm; 13 C NMR (100 MHz, CDCl 3 ) δ=156.8 (C‐2 and C‐6), 139.2 (C‐4), 129.1 (C‐8), 128.7 (C‐9), 127.7 (C‐7), 127.1 (C‐10), 118.7 (C‐3 and C‐5) ppm; HRMS (EI‐QTOF , [M+H] + ): calculated for C 17 H 13 DN: 233.1189; found: 233.1197.…”

“…2‐Phenyl‐6‐( p– tolyl)pyridine ( 3 ad ) [21] : White solid , R f =0.7 (SiO 2 , Hexane/EtOAc=9 : 1); purification system : Column chromatography (SiO 2 , 100–200 mesh) (Hexane/EtOAc=99 : 1); yield : 54 mg (44%); m.p =88–90 °C (Lit [12o] 91–92 °C); 1 H NMR (400 MHz, CDCl 3 ): δ=8.18–8.15 (m, 2H), 8.06 (d, 3 J =8.1 Hz, 2H), 7.85–7.76 (m, 1H), 7.68 (ddd, 3 J =8.0 Hz, 2H), 7.51 (td, 3 J =8.0 Hz, 2H), 7.46–7.42 (m, 1H), 7.31 (dd, 3 J =8.0 Hz, 2H), 2.43 (s, 3H) ppm; 13 C NMR (100 MHz, CDCl 3 ) δ=156.8, 156.7, 139.6, 138.9, 138.8, 137.3, 137.2, 136.8, 129.4, 129.3, 128.9, 128.68, 128.65, 127.0, 126.8, 118.6, 118.3, 118.0, 21.3 ppm; HRMS (EI‐QTOF , [M+H] + ): calculated for C 18 H 16 N: 246.1282; found: 246.1276.…”

“…2‐(4‐Chlorophenyl)‐6‐( p– tolyl)pyridine ( 3 dn ) [21] : White 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 : 74 mg (53%); m.p =112–114 °C (Lit [12o] 113–115 °C); 1 H NMR (400 MHz, CDCl 3 ): δ=8.12–8.04 (m, 4H), 7.80 (t, 3 J =8.0 Hz, 1H; 4‐H), 7.7–7.63 (m, 2H), 7.47 (d, 3 J =8.0 Hz, 2H), 7.32 (d, 3 J =8.0 Hz, 2H) ppm; 13 C NMR (100 MHz, CDCl 3 ) δ=157.0, 156.7, 155.5, 139.1, 138.8, 138.1, 137.5, 137.2, 136.8, 136.5, 135.0, 129.45, 129.38, 128.8, 128.2, 126.8, 118.5, 118.0, 21.3 ppm; HRMS (EI‐QTOF , [M+H] + ): calculated for C 18 H 15 ClN: 280.0893; found: 280.0895.…”

Co(II)‐Catalyzed Oxidation of N,N‐Dimethylaminoethanol: An Efficient Synthesis of Unsymmetrical (2,4‐) and Symmetrical (2,6‐) Diarylpyridines through Annulation of Aromatic Ketones with a Nitrogen Source

“…The synthesis of 2,4‐diaryl unsymmetrical pyridines is usually performed from aryl methyl ketones and an ammonium source using DMSO or DMF as a carbon synthon [13] while α‐C substituted aromatic ketones give 2,6‐aryl symmetrical pyridines (Scheme 2a) [5a,13d,14] . There is only one exception that symmetrical 2.6‐diarylpyridines were achieved from aryl methyl ketones with DMSO employing aliphatic amines as the nitrogen source (Scheme 2b) [15] . Interestingly, when DMEA was employed as the carbon donor, 2,4‐diaryl pyridines were afforded from aryl methyl ketones or para ‐substituted aryl ethyl ketones, while 1,2‐diaryl ethanones, ortho ‐ and meta ‐substituted aryl ethyl ketones, 1,3‐dione, benzoylacetate and benzoylacetonitrile gave 2,6‐diaryl pyridines as the predominant products (Scheme 2c).…”