Download PDF
Synlett 2018; 29(03): 344-348
DOI: 10.1055/s-0036-1591499
letter
© Georg Thieme Verlag Stuttgart · New York

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
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
› Author AffiliationsFinancial assistance from DST-SERB (Project No. SR/S1/OC-30/2011, dated 28-5-12), Government of India, is gratefully acknowledged.
Further Information

Publication History

Received: 05 September 2017

Accepted: 28 September 2017

Publication Date:
03 November 2017 (online)

    Permissions and Reprints All articles of this category


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

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591499.
  • Supporting Information
 

  • References and Notes

  • 1 Wu Y.-B. Ni Z.-Y. Shi Q.-W. Dong M. Kiyota H. Gu Y.-C. Cong B. Chem. Rev. 2012; 112: 5967
    CrossrefPubMed
  • 2 Duke JA. Ayensu ES. Medicinal Plants of China . Vol. 2. Reference Publications; Algonac: 1985: 381
    Google Scholar
  • 3 Su C.-Y. Ming Q.-L. Rahman K. Han T. Qin L.-P. Chin. J. Nat. Med. 2015; 13: 163
  • 4 Wang B.-Q. J. Med. Plant Res. 2010; 4: 2813
  • 5 Nagy G. Günther G. Mathe I. Blunden G. Yang M.-h. Crabb TA. Phytochemistry 1999; 52: 1105
    Crossref
  • 6 Nizamutdinova IT. Lee GW. Lee JS. Cho MK. Son KH. Jeon SJ. Kang SS. Kim YS. Lee JH. Seo HG. Chang KC. Kim HJ. Carcinogenesis 2008; 29: 1885
    CrossrefPubMed
  • 7 Wang D. Xu D. Sun Y. Wu Y. Ma L. Duan J. Glycoconjugate J. 2017; 34: 3
    CrossrefPubMed
  • 8 Zhang Y. Jiang P. Ye M. Kim S.-H. Jiang C. Lü J. Int. J. Mol. Sci. 2012; 13: 13621, and references cited therein
    Crossref
  • 9 Yagi A. Takeo S. J. Gastroenterol. Hepatol. Res. 2015; 4: 1746
  • 10 Gao H. Sun W. Zhao J. Wu X. Lu J.-J. Chen X. Xu Q.-m. Khan IA. Yang S. Sci. Rep. 2016; 6: 33720
    CrossrefPubMed
  • 11 Chen X. Guo J. Bao J. Lu J. Wang Y. Med. Res. Rev. 2014; 34: 768
    Crossref
  • 12 Chen F. Li L. Tian D.-D. BioMed Res. Int. 2017; DOI: 10.1155/2017/9868694.
  • 13 Lee WY. W. Liu KW. K. Yeung JH. K. Cancer Lett. 2009; 285: 46
    CrossrefPubMed
  • 14 Kang HS. Chung HY. Jung JH. Kang SS. Choi JS. Arch. Pharmacal Res. 1997; 20: 496
    CrossrefPubMed
  • 15 Danheiser RL. Casebier DS. Firooznia F. J. Org. Chem. 1995; 60: 8341; and related references cited therein
    Crossref
  • 16 Lee J. Snyder JK. J. Org. Chem. 1990; 55: 4995
    Crossref
  • 17 Wu N. Ma W.-C. Mao S.-J. Wu Y. Jin H. J. Nat. Prod. 2017; 80: 1697
    CrossrefPubMed
  • 18 Jiang Y.-Y. Li Q. Lu W. Cai J.-C. Tetrahedron Lett. 2003; 44: 2073
    Crossref
  • 19 Zhang J. Duan W. Cai J. Tetrahedron 2004; 60: 1665
    Crossref
  • 20 Samanta K. Kar GK. Sarkar AK. Tetrahedron Lett. 2008; 49: 1461
    Crossref
  • 21 Shaik FH. Kar GK. Beilstein J. Org. Chem. 2009; 5: 47
    PubMed
  • 22 Samanta K. Kar GK. Sarkar AK. Tetrahedron Lett. 2012; 53: 1376
    Crossref
  • 23 Sarkar A. Samanta K. Das R. Kar GK. Sarkar AK. ; unpublished results.
  • 24 Miyaura N. Suzuki A. Chem. Rev. 1995; 95: 2457
    Crossref
  • 25 Rao ML. N. Banerjee D. Dhanorkar RJ. Synlett 2011; 273
    Article in Thieme Connect
  • 26 Hesse S. Kirsch G. Synthesis 2001; 755
  • 27 DiPalma JR. Emerg. Med. News 2001; 23: 16 ; available at: http://journals.lww.com/em-news/Fulltext/2001/04000/Bismuth_Toxicity,_Often_Mild,_Can_Result_in_Severe.12.aspx
  • 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%).