Programmed Synthesis of Tetraarylthieno[3,2-b]thiophene by Site-Selective Suzuki Cross-Coupling Reactions of Tetrabromothieno[3,2-b]thiophene

Abstract

Thieno[3,2-b]thiophene is a structural motif that can be found in many important organic materials. A number of mono-, di- and tetraarylthieno[3,2-b]thiophenes are reported herein.

Key words

cross-coupling reactions - palladium - Suzuki–Miyaura reaction - site selectivity - thieno[3,2-b]thiophene

• References and Notes

• 1 Present address: Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France.�
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• 11 General Procedure for the Synthesis of 2-Aryl-3,5,6-tribromothieno[3,2-b]thiophene 2a–j: Toluene was degassed by exchanging between vacuum and a stream of argon (3 ×). 2,3,5,6-Tetrabromothieno[3,2-b]thiophene (1.0 equiv) and Pd(Ph₃P)₄ (0.05–0.10 equiv) were dissolved in this degassed toluene (4 mL) at 60–70 °C. To the obtained solution H₂O (1 mL), K₃PO₄ (2.0 equiv), and arylboronic acid (1.2 equiv) were added. The reaction was vigorously stirred under argon atmosphere at 110 °C until TLC (100% hexane) showed the complete consumption of the starting material. The reaction mixture was filtered to remove insoluble particles. The filtrate was washed several times with H₂O, dried over Na₂SO₄ and concentrated under reduced pressure by rotary evaporation. The residue was purified by SiO₂ column chromatography (100% hexane) to give the product as a white solid. In case of alkoxyphenyl boronic acid, 1,4-dioxane was used instead of toluene (ref. 6b). In fact, toluene–H₂O gave the same result. 2,3,6-Tribromo-5-phenylthieno[3,2-b]thiophene (2a): Starting from 1 (230 mg, 0.5 mmol) and phenylboronic acid (74 mg, 0.6 mmol), 2a was isolated (191 mg, 51%) as white crystals; mp 132–133 °C. ¹H NMR (500 MHz, CDCl₃): δ = 7.68 (m, 2 H, Ar), 7.45 (m, 3 H, Ar). ¹³C NMR (500 MHz, CDCl₃): δ = 99.8, 106.9, 112.5, 128.8, 128.9, 129.0, 132.4, 136.4, 139.8. IR (KBr): 3083 (m), 2929 (s), 2905 (m), 1658 (m), 1610 (m), 1582 (m), 743 (s), 684 (s), 588 (m) cm^–1. HRMS (EI, 70 eV): m/z (M⁺, [⁷⁹Br,⁷⁹Br,⁷⁹Br]) calcd for C₁₂H₅Br₃S₂: 449.7383; found: 449.7392.
• 12 General Procedure for the Synthesis of 2,5-Diaryl-3,6-dibromothieno[3,2-b]thiophenes 4a–c: Toluene was degassed by exchanging between vacuum and a stream of argon (3 ×). 2-Ar¹-3,5,6-tribromothieno[3,2-b]thiophene 2 (1.0 equiv) was dissolved in this degassed toluene (4 mL) at r.t. To the obtained solution were added H₂O (1 mL), K₃PO₄ (2.0 equiv), Pd(Ph₃P)₄ (0.10 equiv) and an Ar²boronic acid (1.2 equiv). The reaction was vigorously stirred under argon atmosphere at 110 °C until TLC (100% hexane) showed the complete consumption of the starting material. The reaction was quenched with H₂O and the mixture was extracted with EtOAc (3 ×). The extracts were collected, dried over Na₂SO₄ and concentrated under reduced pressure by rotary evaporation. The residue was purified by SiO₂ column chromatography (100% hexane → 2% EtOAc in hexane) or by recrystallization from hot toluene to give the product as white crystals. 3,6-Dibromo-2-(3,5-dimethylphenyl)-5-phenylthieno[3,2-b]-thiophene (4b): Starting from 2c (115 mg, 0.25 mmol) and phenylboronic acid (36.6 mg, 0.3 mmol), 4b was isolated (54.7 mg, 46%) as a white solid by SiO₂ column chromatography (100% hexane); mp 185–186 °C. ¹H NMR (500 MHz, CDCl₃): δ = 7.72 (m, 2 H, Ar), 7.48 (m, 2 H, Ar), 7.42 (m, 1 H, Ar), 7.33 (s, 2 H, Ar), 7.06 (s, 1 H, Ar), 2.40 (s, 6 H, 2 × Me). ¹³C NMR (500 MHz, CDCl₃): δ = 21.3 (Me), 99.8, 100.1, 126.8, 128.7, 128.8, 129.1, 130.5, 132.7, 133.0, 138.4, 138.7, 138.8, 139.2, 139.9. IR (KBr): 3027 (w), 2920 (m), 2870 (m), 1653 (m), 1598 (m), 746 (m) cm^–1. HRMS (EI, 70 eV): m/z (M⁺, [⁷⁹Br,⁷⁹Br]) calcd for C₂₀H₁₄Br₂S₂: 475.8904; found: 475.8916.
• 13 Synthesis of 2-(4-Methylstyryl)-3,5,6-tribromothieno[3,2-b]thiophene (6): DMF (4 mL) was saturated with argon by exchanging between vacuum and a stream of argon (3 ×). Pd(OAc)₂ (2.8 mg, 0.0125 mmol, 0.1 equiv) and P(Cy)₃ (7.0 mg, 0.025mmol, 0.2 equiv) were dissolved in this argon-saturated solvent. The brownish yellow solution was stirred at r.t. for further 30 min to produce the catalyst. 2,3,5,6-Tetrabromothieno[3,2-b]thiophene (0.57 mg, 0.125 mmol, 1.0 equiv), Na₂CO₃ (79.5 mg, 0.75 mmol, 6.0 equiv) and 4-methylstyrene (295.5 mg, 12.5 mmol, 10.0 equiv) were added to the solution of the catalyst under a stream of argon. The reaction solution was heated at 90 °C in 5.5 h under argon atmosphere. The progress of the reaction was monitored by TLC (100% hexane). Besides the monoalkenyl substituted derivative, small amounts of di- and trialkenyl-substituted derivatives were also observed. When the starting material was completely consumed as indicated by TLC, the brownish mixture was allowed to cool to r.t., filtered through Celite to remove the brown precipitate. The filtrate was extracted several times with EtOAc, washed with H₂O (3 ×) and dried over anhydrous Na₂SO₄. The solvent was removed under reduced pressure by rotary evaporation and the residue was purified by SiO₂ column chromatography (100% hexane) to give the monoalkenylated 2,3,5,6-tetrabromothieno[3,2-b]thiophene as a yellow solid (76.1 mg, 42%); mp 126–127 °C. ¹H NMR (500 MHz, CDCl₃): δ = 7.40 (d, J = 8.0 Hz, 2 H, Ar), 7.20 (d, J = 16.5 Hz, 1 H), 7.17 (d, J = 8.5 Hz, 2 H, Ar), 6.98 (d, J = 16.0 Hz, 1 H), 2.36 (s, 3 H, Me). ¹³C NMR (500 MHz, CDCl₃): δ = 139.4, 139.1, 138.7, 135.1, 133.4, 131.2, 129.6, 126.7, 118.9, 112.5, 107.2, 102.5, 21.4.
• 14 General Procedure for the Synthesis of 2-Alkynyl-3,5,6-tribromothieno[3,2-b]thiophene 7: A mixture (1:1) of diisopropylamine and THF was saturated with argon by exchanging between vacuum and a stream of argon (3 ×). 2,3,5,6-Tetrabromothieno[3,2-b]thiophene (1.0 equiv), Pd(OAc)₂ (0.1 equiv), Ph₃P (0.2 equiv) and CuI (0.2 equiv) were added to this argon-saturated solution. The suspension was heated to 75 °C while vigorously stirred until it became homogeneous. To the obtained pale yellow mixture, a solution of arylacetylene (1.2 equiv) in argon-saturated THF (1.0 mL) was added dropwise in 30 min. The reaction mixture was heated at 75 °C for 3–6 h. The pale yellow reaction mixture turned reddish brown when the reaction completed as indicated by TLC (100% hexane). The reaction mixture was adsorbed on silica gel, dried under reduced pressure and purified by SiO₂ column chromatography to furnish the monoalkynated derivative. Besides the desired product, a significant amount of the symmetric diynes resulting from the homocoupling reaction of the alkynes was separated. All attempts to reduce this by-product were not successful. 2-(4-Methylphenylethynyl)-3,5,6-tribromothieno[3,2-b]thiophene (7a): Starting from 1 (0.57 mg, 0.125 mmol) and 4-ethynyltoluene (17.4 mg, 0.15 mmol), 7 was isolated (32 mg, yield 52%) as a white solid; mp 193–194 °C. ¹H NMR (500 MHz, CDCl₃): δ = 7.46 (d, J = 8.0 Hz, 2 H, Ar), 7.18 (d, J = 8.0 Hz, 2 H, Ar), 2.38 (s, 3 H, Me). ¹³C NMR (500 MHz, CDCl₃): δ = 139.6, 138.0, 131.7, 131.5, 129.3, 119.0, 114.8, 107.9, 107.1, 99.9, 80.5, 21.6.
• 15 CCDC 971825 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.�