Synlett 2021; 32(18): 1826-1832
DOI: 10.1055/s-0040-1719839
letter

Synthesis of 4,7′-Bibenzo[b]thiophenes Bearing Several Different Substituents at 2-, 2′-, 4′-, and 7-Positions; Structurally Featured Molecular Scaffolds for Selective Substitution

Shinichi Mikami
a   Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai, 980-8578, Japan
,
Akihiro Matsuo
a   Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai, 980-8578, Japan
,
Eunsang Kwon
b   Research and Analytical Center for Giant Molecules, Graduate School of Science, Tohoku University, Aoba-ku, Sendai, 980-8578, Japan
,
Kozo Toyota
a   Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai, 980-8578, Japan
› Author Affiliations
A part of this work was supported by the Japan Society for the Promotion of Science (JSPS KAKENHI Grant Number JP21K02877).


Abstract

Four isomers of 4,7′-bibenzothiophene scaffolds bearing two different halogen (Br, Cl) and triisopropylsilyl substituents have been synthesized from the two multihalobenzo[b]thiophenes via iodoselective Miyaura borylation reaction using potassium benzoate as a base. Further investigation into the reactivity of 4,7′-bibenzothiophenes in substitution reaction, Suzuki–Miyaura cross-coupling reaction, and C–H direct arylation reaction revealed that tetrasubstituted 4,7′-bibenzothiophenes can be synthesized site- (chemo-) selectively, which are promising novel components for molecular architecture.

Supporting Information



Publication History

Received: 16 August 2021

Accepted after revision: 13 September 2021

Article published online:
28 September 2021

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  • 10 Typical Experimental Procedure for Iodoselective Miyaura Borylation Reaction: Synthesis of 4-(7-Bromobenzo[b]thiophene)boronic acid pinacol ester (6a) from 7-Bromo-4-iodobenzo[b]thiophene (2a, Table 1, entry 9) A mixture of 2a (30.6 mg, 0.090 mmol), Pd(PPh3)4 (4.1 mg, 3.513 μmol, 99% purity), (Bpin)2 (25.5 mg, 0.098 mmol, 98% purity), and PhCOOK (42.8 mg, 0.264 mmol, >99.0% purity) in dry DMF (3.0 mL) was stirred at 100 °C for 40 h under nitrogen atmosphere. Then, sat. aq. NaHCO3 was added to the reaction mixture, and the mixture was extracted with hexane–EtOAc (4:1). The organic phase was separated, washed twice with sat. aq. NaHCO3, dried over Na2SO4, and the solvent was removed under reduced pressure to give 6a as a crude product. Spectral Data of the Product 6a A colorless solid; mp 120–123 °C. 1H NMR (400 MHz, CDCl3): δ = 1.39 (12 H, s), 7.50 (1 H , d, 3 J = 7.6 Hz), 7.54 (1 H, d, 3 J = 5.6 Hz), 7.74 (1 H, d, 3 J = 7.6 Hz), 8.10 (1 H, d, 3 J = 5.6 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ = 25.13 (CH3), 84.14 (C–O), 119.81 (C–Br), 126.62 (C–H), 127.12 (C–H), 127.55 (C–H), 133.68 (C–H), 141.59, 145.34. HRMS (APCI): m/z calcd for 12C14 1H16 11B79Br16O2 32S [M+]: 338.0142; found: 338.0142
  • 11 Typical Experimental Procedure for Iodoselective Suzuki–Miyaura Cross-Coupling Reaction: Synthesis of 7-Bromo-4′-chloro-2-triisopropylsilyl-4,7′-bibenzo[b]thiophene (3e, Scheme 4) A mixture of 10a (1.0081 g, 2.035 mmol), the crude product of 7f (ca. 2.022 mmol, prepared from 2f), PdCl2(dppf)·CH2Cl2 (51.8 mg, 62.16 μmol, >98.0% purity), and K3PO4 (1.3490 g, 6.037 mmol, >95.0% purity) in 1,4-dioxane (70.0 mL) and water (7.0 mL) was stirred at 50 °C for 40 h under nitrogen atmosphere. Then, the reaction mixture was cooled to room temperature, and CH2Cl2 was added to the mixture. The mixture was dried over Na2SO4, the solvent was removed under reduced pressure, and the residue was treated with silica gel column chromatography (cyclohexane) and recrystallized from hexane to give 823.1 mg of 3e (1.535 mmol, 76% two-step yield based on 2f). Spectral Data of the Product 3e A colorless solid; mp 175–176 °C. 1H NMR (400 MHz, CDCl3): δ = 1.09 (18 H, d, 3 J = 7.2 Hz), 1.34 (3 H, sept, 3 J = 7.2 Hz), 7.34 (1 H, d, 3 J = 7.6 Hz), 7.38 (1 H, s), 7.41 (1 H, d, 3 J = 8.0 Hz), 7.49–7.52 (2 H, m), 7.57–7.60 (2 H, m). 13C{1H} NMR (100 MHz, CDCl3): δ = 11.86 (–CH–), 18.69 (CH3), 115.70 (C–Br), 122.75 (C–H), 124.76 (C–H), 125.98 (2 C, C–H, C–H), 127.04 (C–H), 128.13 (C–H), 128.44 (C–Cl), 132.60 (C–H), 133.77, 134.00, 138.46, 138.81, 139.92, 141.21, 146.03. HRMS (APCI): m/z calcd for 12C25 1H28 79Br35Cl32S2 28Si [M+]: 534.0268; found: 534.0268
  • 12 CCDC 210850 contains the supplementary crystallographic data for compound 3e. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures