A Suzuki-Coupling-Based Generalized Route for the Synthesis of 2-(2/3-Thienyl)cycloalk-1-ene-1-carbaldehydes as Precursors for Condensed Thienophenanthraquinones

Aparna Sarkar; Rumpa Das; Gandhi K. Kar

doi:10.1055/s-0036-1591499

Synlett, Table of Contents

Synlett 2018; 29(03): 344-348
DOI: 10.1055/s-0036-1591499

letter

A Suzuki-Coupling-Based Generalized Route for the Synthesis of 2-(2/3-Thienyl)cycloalk-1-ene-1-carbaldehydes as Precursors for Condensed Thienophenanthraquinones

Authors

Aparna Sarkar

Department of Chemistry, Presidency University, 86/1 College Street, Kolkata 700073, India Email: gandhi.chem@presiuniv.ac.in
Rumpa Das

Department of Chemistry, Presidency University, 86/1 College Street, Kolkata 700073, India Email: gandhi.chem@presiuniv.ac.in
Gandhi K. Kar*

Department of Chemistry, Presidency University, 86/1 College Street, Kolkata 700073, India Email: gandhi.chem@presiuniv.ac.in

Abstract

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Abstract

A one-pot, simple, and general method is described for the synthesis of 2-(2/3-thienyl)cycloalk-1-ene-1-carbaldehydes by means of a Pd(0)-catalyzed Suzuki coupling reactions of 2- or 3-thienylboronic acids with 2-bromocycloalk-1-en-1-carbaldehyde derivatives.

Key words

Suzuki reaction - coupling - thienylation - bromocycloalkenecarbaldehydes - thienylboronic acids - thienylcycloalkenecarbaldehydes

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References

References and Notes
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28 2-(2/3-Thienyl)cycloalk-1-ene-1-carbaldehydes 2a–g and 3a–g; General ProcedureA stirred mixture of the appropriate 2-bromocycloalk-1-ene-1-carbaldehyde 1a–g (1.0 mmol), thienylboronic acid A–D (1.2 mmol), and Et₃N (2.5 mmol) in anhyd DMF (2 mL) was degassed by bubbling with N₂ for 25 min. Pd(PPh₃)₄ catalyst (1.0 mol%) was added rapidly and the mixture was degassed for a further 10–12 min, then heated at 110–120 °C for 4–12 h under N₂. When the reaction was complete (TLC), the mixture was poured into ice–water (15–20 mL) and extracted thoroughly with Et₂O (3 × 20 mL). The organic layers were combined, washed with ice–water (15 mL), 5% aq NaHCO₃ (3 × 10 mL), and finally ice–water (15 mL). Removal of the solvent under reduced pressure afforded a crude product that was purified by column chromatography [silica gel (100–200 mesh), PE (60–80 °C)–EtOAc (15:1)] or by crystallization from a suitable solvent.2-(2-Thienyl)cyclopent-1-ene-1-carbaldehyde (2a)Light-yellow viscous oil; yield: 128 mg (72%, 0.72 mmol). IR (KBr): 1652.5 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 2.0 (quintet, J = 7.6 Hz, 2 H), 2.78 (t, J = 7.6 Hz, 2 H), 3.04 (t, J = 7.6 Hz, 2 H), 7.11 (dd, J = 4.0, 5.0 Hz, 1 H), 7.27 (br d, J = 4.5 Hz, 1 H), 7.46 (d, J = 5.0 Hz, 1 H), 10.32 (s, 1 H). HRMS (ESI, 70 eV): m/z [M + H]⁺ calcd for C₁₀H₁₁SO: 179.0531; found: 179.0619.5-tert-Butyl-2-(2-thienyl)cyclohex-1-ene-1-carbaldehyde (2b)Colorless solid; yield: 181 mg (73%, 0.73 mmol); mp 68–70 °C. IR (KBr): 1667.16 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 0.93 (s, 9 H), 1.26–1.33 (m, 2 H), 1.94–1.97 (m, 2 H), 2.61–2.72 (m, 3 H), 6.99–7.05 (m, 2 H), 7.41 (dd, J = 0.9, 4.5 Hz, 1 H), 9.78 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 23.94, 24.83, 27.22, 32.31, 36.03, 43.25, 127.12, 127.49, 129.55, 137.44, 140.62, 150.19, 193.08. HRMS (ESI, 70 eV): m/z [M + H]⁺ calcd for C₁₅H₂₁OS: 249.1313; found: 249.1705.2-(3-Thienyl)cyclopent-1-ene-1-carbaldehyde (3a)Pale-yellow oil; yield: 139 mg (78%, 0.78 mmol). IR (KBr): 1650.20 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.86 (quin, J = 7.8 Hz, 2 H), 2.59–2.65 (m, 2 H), 2.82–2.81 (m, 2 H), 7.08 (dd, J = 1.2, 4.8 Hz, 1 H), 7.24–7.30 (m, 2 H), 9.93 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 21.30, 30.90, 39.25, 125.8, 126.21, 127.57, 135.62, 138.69, 155.45, 189.45. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₀H₁₁OS: 179.0452; found: 179.0523.2-(3-Thienyl)cyclooct-1-ene-1-carbaldehyde (3c)Pale-yellow oil; yield: 189 mg (86%, 0.86 mmol). IR (KBr): 1667.84 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.39 (br s, ill split, 4 H), 1.52 (br s, ill split, 4 H), 2.43 (t, J ≈ 6.0 Hz, 2 H), 2.58 (t, J ≈ 6.0 Hz, 2 H), 6.93 (dd, J ≈ 1.2, 5.0 Hz, 1 H), 7.04 (dd, J = 1.6, 3.0 Hz, ill split, 1 H), 7.23 (dd, J ≈ 3.0, 5.0 Hz, 1 H), 9.45 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 23.93, 26.00, 26.39, 28.75, 29.59, 34.65, 125.29, 125.81, 127.65, 139.18, 139.67, 156.25, 192.53. HRMS (ESI, 70 eV): m/z [M + H]⁺ calcd for C₁₃H₁₇OS: 221.0922; found: 221.0478.4-Methyl-1-(3-thienyl)-3,4-dihydronaphthalene-2-carbaldehyde ( 3f₁)Pale-yellow solid; yield: 228 mg (90%, 0.9 mmol); mp 88–90 °C. IR (KBr): 1650.42 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.12 (d, J = 7.2 Hz, 3 H), 2.41 (dd, J = 7.2, 16.4 Hz, 1 H), 2.58 (dd, J = 6.4, 16.4 Hz, 1 H), 2.88 (sext, J = 7.2 Hz, 1 H), 6.85 (br d, J = 7.6 Hz, 1 H), 6.89 (dd, J = 1.2, 5.0 Hz, 1 H), 6.98 (ddd, J = 1.6, 7.2, 7.8 Hz, 1 H), 7.12–7.15 (m, 2 H), 7.17 (ddd, J = 0.8, 7.2, 7.8 Hz, 1 H), 7.27 (dd, J ≈ 3.0, 4.8 Hz, 1 H), 9.57 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 19.87, 28.08, 31.61, 126.15, 126.44, 126.64, 126.88, 128.41, 129.73, 130.76, 133.94, 134.06, 135.19, 143.57, 148.81, 193.30. HRMS (ESI, 70 eV): m/z [M + H]⁺ calcd for C₁₆H₁₅SO: 254.8301: found: 255.0765; [M + Na] calcd for C₁₆H₁₄NaOS: 277.0763; found: 276.7933).1-(2-Acetyl-3-thienyl)-4-methyl-3,4-dihydronaphthalene-2-carbaldehyde( 3f₃)Pale-yellow oil; yield: 175 mg (59%, 0.59 mmol). IR (KBr): 1653.04 (br strong) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.337 & 1.366 (both d, J = 7.2 Hz, total 3 H), 2.282 & 2.350 (both s, total 3 H), 2.465 (dd, J ≈ 9 & 16.8 Hz), 2.688 (dd, J ≈ 6.6 & 14 Hz) & 2.805 (dd, J ≈ 6.2 & 16.8 Hz) (total 2 H), 3.09–3.14 (m, 1 H), 6.90 & 6.74 (both d, J = 7.6 Hz, total 1 H), 7.04 (d, J = 4.8 Hz, 1 H), 7.08–7.15 (m, 1 H), 7.29–7.37 (m, 2 H), 7.71 & 7.94 (both d, J = 5.2 Hz, total 1 H), 9.545 and 9.561 (both s, total 1 H). MS (ES⁺): m/z 297.0 [M + H]⁺, 269.0, 237.0 (purity of the sample as judged by LCMS: 97.88%).

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