Deprotonative Metalation of Chlorothiophene with Grignard Reagents and Catalytic cis-2,6-Dimethylpiperidine under Mild Conditions

Shunsuke Tamba; Kenji Ide; Keisuke Shono; Atsushi Sugie; Atsunori Mori

doi:10.1055/s-0033-1338385

Synlett, Table of Contents

Synlett 2013; 24(9): 1133-1136
DOI: 10.1055/s-0033-1338385

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Deprotonative Metalation of Chlorothiophene with Grignard Reagents and Catalytic cis-2,6-Dimethylpiperidine under Mild Conditions

Shunsuke Tamba

Department of Chemical Science and Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan Fax: +81(78)8036181 Email: amori@kobe-u.ac.jp

,

Kenji Ide

Department of Chemical Science and Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan Fax: +81(78)8036181 Email: amori@kobe-u.ac.jp

,

Keisuke Shono

Department of Chemical Science and Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan Fax: +81(78)8036181 Email: amori@kobe-u.ac.jp

,

Atsushi Sugie

Department of Chemical Science and Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan Fax: +81(78)8036181 Email: amori@kobe-u.ac.jp

,

Atsunori Mori*

Department of Chemical Science and Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan Fax: +81(78)8036181 Email: amori@kobe-u.ac.jp

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Abstract

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Abstract

Deprotonative metalation of chlorothiophene takes place with a catalytic amount of cis-2,6-dimethylpiperidine (DMP) and an alkyl Grignard reagent at room temperature for three hours to give the corresponding thienyl Grignard reagent. Polymerization leading to head-to-tail-type poly(3-substituted thiophene) with the thus metalated chlorothiophene proceeds in the presence of a nickel catalyst bearing an N-heterocyclic carbene (NHC) ligand. Palladium-catalyzed cross-coupling reaction with aryl bromides also gives arylated thiophenes in good to excellent yields while the C–Cl bond remains intact.

Key words

chlorothiophene - palladium - nickel - cross-coupling - Grignard reagent

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References

References and Notes

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7 General procedure for polymerization of chlorothiophene 1: To a solution of 1.02 M EtMgCl (0.50 mL, 0.5 mmol) in THF were added 2-chloro-3-hexylthiophene (1; 0.5 mmol, 101 mg) and cis-2,6-dimethylpiperidine (0.05 mmol 6.7 μL) dropwise, and the resulting mixture was stirred at room temperature for 3 h. THF (4.5 mL) and NiCl₂(PPh₃)IPr (3.9 mg, 0.005 mmol) were successively added and stirring was continued at 25 °C for 24 h. Hydrochloric acid (1.0 M, 20 mL) and methanol (50 mL) were added to form a precipitate. The mixture was filtered and the residue was washed with methanol repeatedly to leave a dark-purple solid, which was dried under reduced pressure to afford poly(3-hexylthiophene) (3; 50 mg, 59% yield; M _n = 13200, M _w/M _n= 1.39).

PEPPSI™: Pyridine-Enhanced Precatalyst Preparation Stabilization and Initiation. SIPr: 1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene. See:

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10 General procedure for arylation of chlorothiophene: To a solution of 1.02 M EtMgCl (0.75 mL, 0.75 mmol) in THF were added 2-chloro-3-hexylthiophene (1; 0.5 mmol, 101 mg) and cis-2,6-dimethylpiperidine (0.05 mmol 6.7 μL) dropwise at room temperature and the resulting mixture was stirred at room temperature for 3 h. THF (2 mL), 4-bromotoluene (4a; 0.9 mmol, 0.11 mL), and PdCl₂(dppf) (8.2 mg, 0.01 mmol) were successively added and stirring was continued at room temperature for 15.5 h. The reaction mixture was poured into water and the organic materials were extracted with diethyl ether. The organic layer was washed with water twice and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to leave a crude oil, which was purified by column chromatography on silica gel using hexane as an eluent to afford 2-chloro-3-hexyl-5-(4′-methylphenyl)thiophene (5a; 101 mg). ¹H NMR (300 MHz, CDCl₃): δ = 0.89 (t, J = 6.9 Hz, 3 H), 1.25–1.43 (m, 6 H), 1.50–1.68 (m, 2 H), 2.35 (s, 3 H), 2.56 (t, J = 7.7 Hz, 2 H), 6.96 (s, 1 H), 7.16 (d, J = 8.1 Hz, 2 H), 7.39 (d, J = 8.2 Hz, 2 H); ¹³C NMR (75 MHz, CDCl₃): δ = 14.07, 21.13, 22.59, 28.15, 28.93, 29.59, 31.63, 123.02, 123.07, 125.24, 129.56, 131.08, 137.51, 140.21, 140.62; IR (neat): 809, 1041, 1453, 1513, 2856, 2925, 2954; HRMS (DART-ESI+): m/z [M + H]⁺ calcd for C₁₇H₂₂ ³⁵ClS: 293.1131; found: 293.1131.

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13 Dohi, Kita, and co-workers recently reported an efficient three-step synthesis of this structure, see: Dohi T, Yamaoka N, Nakamura S, Sumida K, Morimoto K, Kita Y. Chem. Eur. J. 2013; 19: 2067

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