Efficient Synthesis of Chiral 2,2′-Bis-bipyridines

Abstract

Chiral 2,2′-bis-bipyridines, where the two bipyridine moieties are connected through various bridging groups are obtained by Suzuki cross-coupling reactions. The resulting metal chelators represent a new variety in the class of the CHIRAGEN ligands.

Key words

chiral ligands - cross-coupling - macrocycles - supramolecular chemistry - stereoselectivity

References

• 1 Hayoz P. von Zelewsky A. Tetrahedron Lett.  1992,  33:  5165 
• 2 From CHIRality GENerators: Hayoz P. von Zelewsky A. Stoeckli-Evans H. J. Am. Chem. Soc.  1993,  115:  5111 
• 3 Fletcher NC. Keene FR. Ziegler M. Stoeckli-Evans H. Viebrock H. von Zelewsky A. Helv. Chim. Acta  1996,  79:  1192 
• 4 Mamula O. von Zelewsky A. Bark T. Bernadinelli G. Angew. Chem. Int. Ed.  1998,  37:  289 ; Angew. Chem. 1998, 110, 301
• 5 Muerner H. von Zelewsky A. Hopfgartner G. Inorg. Chim. Acta  1998,  271:  36 
• 6 Mamula O. von Zelewsky A. Bark T. Bernadinelli G. Angew. Chem. Int. Ed.  1999,  38:  2945 ; Angew. Chem. 1999, 111, 3129
• 8 Rapenne G. Dietrich-Buchecker C. Sauvage J.-P. J. Am. Chem. Soc.  1996,  118:  10932 
• 11 Miyaura N. Yanagi T. Suzuki A. Synth. Commun.  1981,  11:  513 
• 16 Coutts IGC. Goldschmid HR. Musgrave OC. J. Chem. Soc. C  1970,  488 
• 17 Ishiyama T. Murata M. Miyaura N. J. Org. Chem.  1995,  60:  7508 

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Düggeli, M.; Goujon-Ginglinger, C.; Richard Ducotterd, S.; Mauron, D.; Bonte, C.; von Zelewsky, A.; Stoeckli-Evans H. in preparation.

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A ligand with [B] = ferrocenyl was also synthesized using a slightly different method [B. Quinodoz and A. von Zelewsky, in preparation].

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Commercially available from the Aldrich Chem. Co.

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Procedure for the Preparation of Bis-5,6-pinene Bi-pyridine-[ p -phenyl](3)
Under argon atmosphere, in a 50 mL two-necked round-bottomed flask equipped with a reflux condenser and a wisp, 400 mg (1.21 mmol) of 6′-bromo-5,6-pinene-bipyridine were dissolved in 10 mL toluene and 100 mg (0.64 mmol) of 1,4 phenylenediboronic acid were dissolved in 5 mL of EtOH. Beside, 3.18 mg of Na₂CO₃ were dissolved in 15 mL H₂O under argon too. The solution of K₂CO₃ was put into the mixture with a syringe and 88 mg (0.76 mmol) of Pd(PPh₃)₄ was added as catalyst. The mixture was heated at 100 °C during 20 h and the reaction was followed by TLC. After addition of 10 drops of H₂O₂ 30%, 10 mL of CH₂Cl₂ and 10 mL of H₂O was added. The aq phase was extracted 3 × with CH₂Cl₂. After drying over MgSO₄ and evaporation of the solvent. 200 mg of a white product were obtained after several purifications by chromatography (SiO₂, hexane:EtOAc:NEt₃, 5:1:0.1, yield: 29%). ^¹ H NMR (300 MHz, CDCl ₃ ): δ 8.38-8.37 (m, 2 H, H₍₃₎, H_{(3 ′ )}), 8.30 (s, 1 H, H _(a)), 7.90 (d × d, 1 H, H_{(4 ′ )}), 7.82 (d, 1 H, H_{(5 ′ )}; ³ J _{5 ′ -4 ′} = 7.8 Hz), 7.41 (d, 1 H, H₍₄₎), 3.20 (d, 2 H, H₍₈₎; ³ J _8-7 = 2.7 Hz), 2.85 (d × d, 1 H, H₍₅₎,), 2.82-2.71 (m, 1 H, H_(9exo)), 2.41-2.43 (m-sept, 1 H, H₍₇₎), 1.44 (s, 3 H, H₍₁₀₎), 1.38 (d, 1 H, H_(9endo); ³ J _9endo-9exo = 9.3 Hz), 0.7 (s, 3 H, H₍₁₁₎). ^¹³ C NMR (300 MHz, CDCl ₃ ): δ = 156.31, 156.28, 154.0, 142.30, 140.0, 137.70, 134.20, 128.9, 127.25, 119.91, 119.46, 118.62, 46.56, 40.26, 39.63, 36.62, 31.98, 26.10, 21.39. HRMS: Calcd 575.3114; found: 575.3163.

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Procedure for the Preparation of Bis-5,6-pinene Bi- pyridine-[2,5-tiophene](4)
Similar to procedure given in ref. [12] . ^¹ H NMR (300 MHz, CDCl ₃ ): δ = 8.34-8.28 (m, 2 H, H₍₃₎, H_{(3 ′ )}), 7.76 (d × d, 1 H, H_{(4 ′ )}), 7.67 (m, 2 H, H_{(5 ′ ),} H _(a)), 7.40 (d, 1 H, H₍₄₎; ³ J _3-4 = 7.8 Hz), 3.20 (d, 2 H, H₍₈₎; ³ J = 2.7 Hz; ³ J _8-7 = 2.7 Hz), 2.85 (d × d, 1 H, H₍₅₎); ³ J _5-9exo = 5.5 Hz, ³ J _5-9endo = 5.8 Hz, 2.82-2.71 (m, 1 H, H_(9exo)), 2.41-2.43 (m-sept, 1 H, H₍₇₎), 1.44 (s, 3 H, H₍₁₀₎), 1.38 (d, 1 H, H_(9endo); ³ J _9endo-9exo = 9.3 Hz), 0.7 (s, 3 H, H₍₁₁₎). ^¹³ C NMR (300 MHz, CDCl₃): δ = 156.35, 153.28, 151.77, 146.77, 142.52, 137.61, 133.98, 128.38, 119.11, 118.45, 118.14, 46.59, 40.29, 39.58, 36.72, 32.01, 26.15, 21.40. HRMS: Calcd 581.2745; found: 581.2725. 23% Yield.

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Procedure for the Preparation of Bis-5,6-pinene Bi- pyridine-[stilbene](5)
Similar to procedure given in ref. [12] . ^¹ H NMR (300 MHz, CDCl ₃ ): δ = 8.33 (d, 1 H, H₍₃₎; ³ J _3-4 = 8.1 Hz), 8.07 (d, 1 H, H_{(3 ′ )}; ³ J _{3 ′ -4’} = 7.8 Hz), 7.62 (d × d, 1 H, H_{(4 ′ )}), 7.41 (d, 1 H, H₍₄₎; ³ J _4-3 = 7.8 Hz), 7.38 (d, 1 H, H_{(5 ′ )}; ³ J _{5 ′ -4"} = 5.1 Hz), 7.24 (s, 2 H, H _(c)H _(b)), 7.12 (s, 1 H, H _(a)), 3.20 (d, 2 H, H₍₈₎; ³ J _8-7 = 2.7 Hz), 2.85 (d × d, 1 H, H₍₅₎), 2.82-2.71 (m, 1 H, H_(9exo)), 2.41-2.43 (m-sept., 1 H, H₍₇₎), 1.44 (s, 3 H, H₍₁₀₎), 1.38 (d, 1 H, H_(9endo); ³ J _9endo-9exo = 9.3 Hz), 0.7 (s, 3 H, H₍₁₁₎). ^¹³ C NMR (300 MHz, CDCl ₃ ): δ = 155.95, 148.50, 142.34, 139.10, 133.83, 131.48, 130.09, 127.75, 127.24, 127.13, 119.40, 119.30, 118.43, 46.54, 40.23, 39.59, 36.71, 31.93, 29.80, 26.10, 21.36. HRMS: Calcd 677.3647; found: 677.3638. 16% Yield.

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Commercially available from the Aldrich Chem. Co.

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Procedure for the Preparation of Bis-5,6-pinene Bi- pyridine-[ m -phenyl](6)
Similar to procedure given in ref. [12] ^¹ H NMR (300 MHz, CDCl ₃ ): δ = 8.90 (s, 1 H, H _{(a)normally triplet}), 8.40-8.36 (m, 2 H, H _(b), H₍₃₎), 8.23 (d, 1 H, H_{(3 ′)}), 7.93-7.83 (m, 2 H, H₍₄₎, H _(c)), 7.65 (d × d, 1 H, H_{(4 ′)}; ³ J _{4 ′-3 ′} = 7.5 Hz, ³ J _{4 ′-5 ′} = 7.5 Hz), 7.38 (d, 1 H, H_{(5 ′)}; ³ J _{5 ′-4"} = 7.8 Hz), 3.20 (d, 2 H, H₍₈₎, ³ J _8-7 = 2.7 Hz), 2.85 (d × d, 1 H, H₍₅₎; ³ J _5-9exo = 5.4 Hz, ³ J _5-9endo = 5.7 Hz), 2.82-2.71 (m, 1 H, H_(9exo)), 2.41-2.43 (m-sept., 1 H, H₍₇₎; ³ J = 3 Hz), 1.44 (s, 3 H, H₍₁₀₎), 1.38 (d, 1 H, H_(9endo); ³ J _9endo-9exo = 9.3 Hz), 0.7 (s, 3 H, H₍₁₁₎). ^¹³ C NMR (300 MHz, CDCl ₃ ): δ = 156.22, 156.17, 153.47, 142.34, 137.67, 133.95, 129.11, 127.65, 127.57, 125.60, 123.13, 119.89, 119.83, 119.28, 46.57, 40.29, 39.63, 32.02, 30.74, 26.12, 21.38. HRMS: Calcd 575.3114; found: 575.3157.30% Yield.