Site-Selective Suzuki-Miyaura Reactions of 2,3,5-Tribromothiophene

Abstract

The first Suzuki-Miyaura reactions of 2,3,5-tribromothiophene are reported. These reactions provide a convenient and site-selective approach to 5-aryl-2,3-dibromothiophenes, 2,5-diaryl-3-bromothiophenes, and 2,3,5-triarylthiophenes.

Key words

catalysis - palladium - Suzuki-Miyaura reaction - site selectivity - thiophene

References and Notes

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General Procedure for the Synthesis of 2,3-Dibromo-5-arylthiophene 2
To a mixture of 1 (0.159 g, 0.5 mmol), arylboronic acid (0.55 mmol), Pd(PPh₃)₄ (5 mol%) were added a mixture of 1,4-dioxane and toluene (1:1, 5 mL) and an aq solution of K₂CO₃ (2 mL, 2 M) under argon atmosphere. The reaction mixture was stirred at 100 ˚C for 8 h and was subsequently allowed to cool to 20 ˚C. The solution was poured into H₂O and CH₂Cl₂ (25 mL each) and the organic and the aqueous layer were separated. The latter was extracted with CH₂Cl₂ (3 × 25 mL), dried (Na₂SO₄), filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (flash silica gel, n-heptane).
Synthesis of 2,3-Dibromo-5- p -tolylthiophene (2a)
Starting with 1 (0.320 g, 1.0 mmol) and 4-tolylboronic acid (0.149 g, 1.1 mmol), 2a was isolated (0.150 g, 47%) as a colorless solid, mp 83-85 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 2.26 (s, 3 H, CH₃), 6.94 (s, 1 H, Ar), 7.08 (d, ^³ J = 8.0 Hz, 2 H, Ar), 7.26 (d, ^³ J = 8.2 Hz, 2 H, Ar). ^¹³C NMR (62 MHz, CDCl₃): δ = 21.3 (CH₃), 109.4, 114.5 (CBr), 125.0, 125.3, 128.7, 129.4, 129.8 (CH, Ar), 130.0, 138.6, 145.6 (C). IR (KBr): ν = 3091 (w), 3019 (w), 2918 (w), 2852 (w), 1498 (m), 1433 (w), 1118 (w), 997 (w), 821 (w), 801 (m), 550 (w) cm^-¹. GC-MS (EI, 70 eV): m/z (%) = 334 [M⁺, ^8¹Br, ^8¹Br], 332 (100) [M⁺, ^8¹Br, ⁷⁹Br], 331 (16) [M⁺], 330 (49) [M⁺, ⁷⁹Br, ⁷⁹Br], 172 (35), 171 (30), 86 (11). HRMS (EI, 70 eV): m/z calcd for C₁₁H₈Br₂S [M⁺, ^8¹Br, ⁷⁹Br]: 331.86875; found: 331.86882.

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