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

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.

Key words

bibenzothiophene building block - multihalomolecular scaffold - molecular architecture - orthogonal structure

• References and Notes

• 1 Miyaura N, Suzuki A. Chem. Rev. 1995; 95: 2457
• 2a Pivsa-Art S, Satoh T, Kawamura Y, Miura M, Nomura M. Bull. Chem. Soc. Jpn. 1998; 71: 467
• 2b Liégault B, Lapointe D, Caron L, Vlassova A, Fagnou K. J. Org. Chem. 2009; 74: 1826
• 2c Schipper DJ, Fagnou K. Chem. Mater. 2011; 23: 1594
• 2d Gorelsky SI, Lapointe D, Fagnou K. J. Org. Chem. 2012; 77: 658
• 2e Kuwabara J, Sakai M, Zhang Q, Kanbara T. Org. Chem. Front. 2015; 2: 520
• 2f Luo B, Liu H, Lin Z, Jiang J, Shen D, Liu R, Ke Z, Liu F. Organometallics 2015; 34: 4881
• 3a Dewar JS, Harget AJ, Trinajstic N, Worley SD. Tetrahedron 1970; 26: 4505
• 3b Katritzky AR, Barczynski P, Musumarra G, Pisano D, Szafran M. J. Am. Chem. Soc. 1989; 111: 7
• 4 Bergmann D, Hinze J. Angew. Chem., Int. Ed. Engl. 1996; 35: 150
• 5 Ie Y, Hirose T, Aso Y. J. Mater. Chem. 2009; 19: 8169
• 6a Mikami S, Tanaka H, Kishi H, Yoshida S, Toyota K. Heterocycles 2018; 96: 1529
• 6b Mikami S, Tanaka H, Kishi H, Yoshida S, Toyota K. Phosphorus, Sulfur Silicon Relat. Elem. 2019; 194: 768
• 6c Toyota K, Mutoh H, Kishi H, Mikami S, Tanaka H, Yoshida S, Naganuma D. Heterocycles 2019; 98: 1355
• 7 Yoshida K, Shida H, Takahashi H, Yanagisawa A. Chem. Eur. J. 2011; 17: 344

For example:
• 8a Cariou M, Douadi T, Simonet J. New J. Chem. 1995; 19: 65
• 8b Tahara Y, Matsubara R, Shibata T. Heterocycles 2015; 90: 1094
• 9 Ishiyama T, Murata M, Miyaura N. J. Org. Chem. 1995; 60: 7508
• 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