Efficient Synthesis of 2-Pyridylenynes and Application in Cobalt-Catalysed Benzannulation Reactions

Abstract

The cobalt-catalysed benzannulation of 2-pyridine-substituted enynes gave 2,3-bis(2-pyridyl)styrenes in moderate yields. The reaction with dibromomethane as well as diiodomethane generated the corresponding planar-chiral bispyridinium salts in good yields. On the other hand, the transformations with reagents of the type RCHBr₂ to afford diastereomeric products led to the desired conversion. However, these products could not be obtained in pure form.

Key words

benzannulation - cobalt - enynes - pyridines - styrenes

• References and Notes

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• 4 General Procedure for the Stepwise Sonogashira Reaction of 2-Iodo- and 2-Bromopyridines of Type 4 PdCl₂(PPh₃)₂ (42 mg, 2.0 mol%), CuI (11 mg, 2.0 mol%), and Ph₃P (32 mg, 4.0 mol%) were suspended in toluene (10 mL). To the suspension, degassed i-Pr₂NH (1.0 mL, 7.00 mmol, 2.3 equiv), 2-iodo- or 2-bromopyridine 4 (3.00 mmol, 1.0 equiv) and ethynyltrimethylsilane (0.5 mL, 3.60 mmol, 1.2 equiv) were added successively, and the reaction mixture was stirred at r.t. for 2 d. K₂CO₃ (2.90 g, 21.0 mmol, 7.0 equiv) and MeOH (20 mL) were added to the mixture and stirred at r.t. until complete conversion was observed by TLC or GC–MS analysis. The reaction mixture was concentrated under reduced pressure, H₂O was added followed by extraction with CH₂Cl₂, and dried over Na₂SO₄. The crude product was purified by column chromatography to give the desired product 5 [the same procedure was used for the second Sonogashira reaction with vinyl bromide (1 M in THF, 1.2 equiv) instead of ethynyltrimethylsilane].
• 5 Severin R, Reimer J, Doye S. J. Org. Chem. 2010; 75: 3518
• 6 One-Pot Procedure for the Synthesis of 2-Pyridyl enynes of Type 6 PdCl₂(PPh₃)₂ (42 mg, 2.0 mol%), CuI (11 mg, 2.0 mol%), and Ph₃P (32 mg, 4.0 mol%) were suspended in THF (10 mL). To the suspension, degassed i-Pr₂NH (1.0 mL, 7.00 mmol, 2.3 equiv), 2-iodo- or 2-bromopyridine 4 (3.00 mmol, 1.0 equiv), and ethynyltrimethylsilane (0.5 mL, 3.60 mmol, 1.2 equiv) were added successively, and the reaction mixture was stirred at r.t. for 2 d. KOH (1.18 g, 21.0 mmol, 7.0 equiv) in MeOH–H₂O (15 mL, 4:1 v/v) were added to the mixture and stirred at r.t. for 3.5 h. Then vinyl bromide [3.6 mL (1 M in THF), 3.60 mmol, 1.2 equiv] were added and stirred at r.t. for another 16 h. The reaction mixture was concentrated under reduced pressure, H₂O was added followed by extraction with CH₂Cl₂, and dried over Na₂SO₄. The crude product was purified by column chromatography to give the desired product 6.
• 7 General Procedure for the Cobalt-Catalysed Benzannulation Reaction of 2-Pyridyl Enynes of Type 6 CoBr₂(dppp) (126 mg, 20 mol%), Zn powder (26 mg, 40 mol%), and ZnI₂ (128 mg, 40 mol%) were dissolved in DMSO (1.5 mL), and the enynes of type 6 were added (1.00 mmol). The reaction mixture was stirred at r.t. until complete conversion was observed by TLC or GC–MS analysis. A solution of EDTA (584 mg, 2.00 mmol) in aq NH₃ buffer (20 mL, pH 10) was added followed by extraction with CH₂Cl₂. The organic layers were combined, dried over Na₂SO₄, the solvent was evaporated, and the crude product was purified by column chromatography to give the desired styrene derivatives 7.
• 8 Almarzoqi B, George AV, Isaacs NS. Tetrahedron 1986; 42: 601
• 9 The supplementary crystallographic data can be obtained free of charge from The Cambridge Crystallographic Data Centre; CCDC 924471.
• 10 Representative Procedure for the Synthesis of the Bispyridinium Salt 8a CH₂Br₂ (20 μL, 0.29 mmol, 1.45 equiv) was added to a solution of 2,3-bis(2-pyridyl)styrene 7a (52 mg, 0.20 mmol, 1.0 equiv) in MeCN (1.0 mL) and was stirred at 70 °C for 3 d. The solvent was removed, the residue washed successively with 3.0 mL CH₂Cl₂, Et₂O, and pentane and dried under reduced pressure to give the desired product 8a.