C−H Arylation of Thiophenes with Aryl Bromides by a Parts-per-Million Loading of a Palladium NNC-Pincer Complex

Anggi Eka Purta; Shun Ichii; Aya Tazawa; Yasuhiro Uozumi

doi:10.1055/s-0040-1707213

Synlett, Table of Contents

Synlett 2020; 31(16): 1634-1638
DOI: 10.1055/s-0040-1707213

letter

C−H Arylation of Thiophenes with Aryl Bromides by a Parts-per-Million Loading of a Palladium NNC-Pincer Complex

Anggi Eka Purta

^aInstitute for Molecular Science (IMS), Myodaiji, Okazaki 444-0864, Japan

,

Shun Ichii

^aInstitute for Molecular Science (IMS), Myodaiji, Okazaki 444-0864, Japan

^bThe Graduate University for Advanced Studies, SOKENDAI, Myodaiji, Okazaki 444-0864, Japan Email: uo@ims.ac.jp

,

Aya Tazawa

^aInstitute for Molecular Science (IMS), Myodaiji, Okazaki 444-0864, Japan

,

Yasuhiro Uozumi ∗

^aInstitute for Molecular Science (IMS), Myodaiji, Okazaki 444-0864, Japan

^bThe Graduate University for Advanced Studies, SOKENDAI, Myodaiji, Okazaki 444-0864, Japan Email: uo@ims.ac.jp

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Abstract

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Abstract

A palladium NNC-pincer complex efficiently catalyzed the direct arylation of thiophene derivatives with extremely low palladium loadings of the order of parts per million. Thus, the reaction of various thiophenes with aryl bromides in the presence of 25–100 mol ppm of chlorido[(2-phenyl-κ-C ²)-9-phenyl-1,10-phenanthroline-κ²-N,N′]palladium(II) NNC-pincer complex, K₂CO₃, and pivalic acid in N,N-dimethylacetamide afforded the corresponding 2- or 5-arylated thiophenes in good to excellent yields. A combination of the present C–H arylation and Hiyama coupling with the same NNC-pincer complex provides an efficient synthesis of unsymmetrical 2,5-thiophenes with catalyst loadings at mol ppm levels.

Key words

C–H functionalization - arylation - palladium catalysis - pincer complexes - thiophenes - Hiyama coupling

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References

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17 C–H Arylation of 1-Benzothiophene (1); General Procedure A Schlenk tube containing a magnetic stirrer bar was charged with 1-benzothiophene (1; 2 mmol), the appropriate aryl bromide 2 (1 mmol), K₂CO₃ (0.5 mmol), pivalic acid (0.3 mmol), a 0.5 mM solution of DPP-NNC in anhyd DMA (100 μL; 5 ×10^–5 mmol Pd), and anhyd DMA (1.9 mL). The resulting mixture was degassed and stirred vigorously at 150 °C under N₂ for 20 h. The mixture was then cooled to r.t., diluted with EtOAc, transferred to a separatory funnel, and washed with water (×3). The organic layer was dried (Na₂SO₄) and concentrated in vacuo, and the resulting residue was purified by chromatography (silica gel, hexane/AcOEt).
18 2-(2,6-Dimethylphenyl)benzo[b]thiophene (3j) White solid; yield: 218 mg (92%). ¹H NMR (396 MHz, CDCl₃): δ = 7.81 (d, J = 8.3 Hz, 1 H), 7.75 (d, J = 7.1 Hz, 1 H), 7.52 (s, 1 H), 7.36–7.24 (m, 4 H), 6.98 (s, 1 H), 2.37 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 144.6, 140.7, 139.4, 138.5, 134.1, 130.1, 124.4, 124.3, 124.1, 123.5, 122.2, 119.2, 21.26. HRMS (FAB): m/z [M⁺] calcd for C₁₆H₁₄S: 238.0816; found: 238.0823. 2-(2-Isopropylphenyl)benzo[b]thiophene (3n) Colorless oil; yield: 152 mg (60%). ¹H NMR (396 MHz, CDCl₃): δ = 7.84 (d, J = 7.9 Hz, 1 H), 7.79 (d, J = 7.1 Hz, 1 H), 7.42–7.31 (m, 5 H), 7.22–7.20 (m, 1 H), 7.18 (s, 1 H), 3.38–3.31 (m, 1 H), 1.22 (d, J = 6.7 Hz, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 147.8, 143.3, 140.3, 140.0, 133.0, 131.0, 129.0, 125.7, 125.4, 124.3, 124.0, 123.4, 123.1, 122.0, 29.7, 24.4. EI-MS: m/z = 252 [M⁺]. HRMS (FAB): m/z [M⁺] calcd for C₁₇H₁₆S: 252.0973; found: 252.0961. 2-(2,6-Difluorophenyl)benzo[b]thiophene (3o) White solid; yield: 152 mg (62%). ¹H NMR (396 MHz, CDCl₃): δ = 7.88–7.83 (m, 2 H), 7.74 (s, 1 H), 7.38–7.35 (m, 2 H), 7.31–7.25 (m, 1 H), 7.10–7.00 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 160.1 (dd, J = 252.9, 6.8 Hz), 140.3 (t, J = 2.9 Hz), 139.2, 129.7 (t, J = 2.8 Hz), 129.2 (t, J = 10.5 Hz), 126.2 (t, J = 5.7 Hz), 124.8, 124.3, 123.9, 121.8, 112.1 (q, J = 17.2 Hz), 111.9 (dd, J = 24.9, 1.9 Hz). EI-MS: m/z = 246 [M⁺]. HRMS (FAB): m/z [M⁺] calcd for C₁₄H₈F₂S: 246.0315; found: 246.0323.
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