Palladium-Catalyzed C-H Arylation of Thieno[2,3-b]thiophene: An Approach to Novel 2,5-Diaryl/Heteroaryl Thieno[2,3-b]thiophenes

Abstract

Direct C-H arylation of thieno[2,3-b]thiophene is reported under Pd(OAc)₂/n-Bu₄NBr catalysis and provides rapid entry into the first examples of 2,5-diaryl thienothiophenes. The reaction works well with either electron-deficient or electron-rich halo-arenes, giving satisfactory yields of diarylation products. Novel push-pull thienothiophenes bearing electron-deficient aryl groups (λ_max 318-373 nm and λ_cut-off 430 nm) are potentially interesting for their photonic properties.

palladium catalysis - C-H arylation - thieno[2,3-b]thiophene - 2,5-diarylthieno[2,3-b]thiophenes - UV-visible

References and Notes

1 Raimundo J.-M. Blanchard P. Gallego-Planas N. Mercier N. Ledoux-Rak I. Hierle R. Roncali J. J. Org. Chem.  2002,  67:  205 

2a Greenwald Y. Poplawski J. Ehrenfreund E. Speiser S. Synth. Met.  1997,  85:  1353 

2b Semenikhin OA. Ovsyannikava EV. Alpatova NM. Rotenberg ZA. Kazarinov VE. J. Electroanal. Chem.  1999,  463:  190 

3 Huang B. Li J. Jiang Z. Qin J. Yu G. Liu Y. Macromolecules  2005,  38:  6915 

4 Mitschke U. Osteritz EM. Debaerdemaeker T. Sokolowski M. Bauerle P. Chem. Eur. J.  1998,  4:  2211 

5a Blenkle M. Boldt P. Bräuchle C. Grahn W. Ledoux I. Nerenz H. Stadler S. Wichern J. Zyss J. J. Chem. Soc., Perkin Trans. 2  1996,  1377 

5b Boldt P. Blenkle M. Cabrera I. Lupo W. Hickel W. Nonlinear Opt.  1994,  8:  173 

6 Albota M. Betjonne D. Bredas J.-J. Ehrlich JE. Fu J.-Y. Heikeal AA. Hess SE. Kogej T. Levin MD. Marder SR. McCord-Maughon D. Perry JW. Rockel H. Rumi M. Subramaniam G. Webb WW. Wu X.-L. Xu C. Science  1998,  281:  1653 

7 Prim D. Kirsch G. J. Chem. Soc., Perkin Trans. 1  1994,  18:  2603 

8 For a solitary report describing introduction of thiophene at the C2,C5 positions of thieno[2,3-b]thiophene by Stille’s protocol, see: Heeney M. Bailey C. Genevicius K. Shukunov M. Sparrowe D. Tierney S. McCulloch I. J. Am. Chem. Soc.  2005,  127:  1078 

9a Mashraqui SH. Hariharasubramanian H. Kumar S. Synthesis  1999,  2030 

9b Mohareb RM. Sherif SM. Habashi A. Abdel-Sayed NI. Osman SS. Collect. Czech. Chem. Commun.  1995,  60:  1578 

9c El-Saghier AMM. Bull. Chem. Soc. Jpn.  1993,  66:  2011 

9d Dejong RL. Brandsma L. Synth. Commun.  1991,  21:  145 

9e Junjappa H. Ila H. Asokan CV. Tetrahedron  1990,  46:  5423 

9f Dalgaard L. Jensen L. Lawesson SO. Tetrahedron  1974,  30:  93 

9g Abdel-Ghany H. Khodairy A. Phosphorous, Sulfur Silicon Relat. Elem.  2000,  166:  45 

10a 3,4-Diaryl/heteroaryl thieno[2,3-b]thiophenes are well known, see: Mashraqui SH. Ashraf M. Harini H. Kellogg RM. Meetsma A. J. Mol. Struct.  2004,  689:  107 

10b Mashraqui SH. Sangvikar Y. Ashraf M. Kumar S. Daub ETH. Tetrahedron  2005,  61:  3507 

11a Hassan J. Sevignon M. Gozzi C. Schulz E. Lemaire M. Chem. Rev.  2002,  102:  1359 

11b Littke AF. Fu GC. Angew. Chem. Int. Ed.  2002,  41:  4176 

11c Espinet P. Echavarren AM. Angew. Chem. Int. Ed.  2004,  43:  4704 

11d Fang Y.-Q. Hanan GS. Synlett  2003,  852 

11e Wallace DJ. Chen C.-Y. Tetrahedron Lett.  2002,  43:  6987 

11f Miyaura N. Suzuki A. Chem. Rev.  1995,  95:  2457 

12 Akita Y. Itagaki Y. Takaziwa S. Ohta A. Chem. Pharm. Bull.  1989,  37:  1477 

For leading references, see:

13a Glover B. Harvey KA. Liu B. Sharp MJ. Tymoschenko MF. Org. Lett.  2003,  5:  301 

13b Masui K. Mori A. Okano K. Takamura K. Kinoshita M. Ikeda T. Org. Lett.  2004,  6:  2011 

13c Lane SB. Sames D. Org. Lett.  2004,  6:  2897 

13d Sezen B. Sames D. J. Am. Chem. Soc.  2003,  125:  5274 

13e Fujita Y. Hiraki K. Kiamogawa Y. Suenaga M. Toggoh K. Fujiwara Y. Bull. Chem. Soc. Jpn.  1989,  62:  1081 

13f Jia C. Lu W. Kitamura T. Fujiwara Y. Org. Lett.  1999,  13:  2097 

14 Chabert JFD. Gozzi C. Lemaire M. Tetrahedron Lett.  2002,  43:  1829 

15 Chabert JFD. Joucla L. David E. Lemaire M. Tetrahedron  2004,  60:  3221 

16 For a recent review on direct C-H arylations, see: Campeau C.-L. Fagnou K. Chem. Commun.  2006,  1253 

17

Typical procedure: To a solution of 1 (0.168 g, 1 mmol) and appropriate aryl halide (2.1 mmol) in dry DMF (15 mL) were introduced anhyd K₂CO₃ (0.600 g, ca. 2 mmol), n-Bu₄NBr (0.644 g, 2 mmol) and Pd(OAc)₂ (10 mg). The reaction mixture was stirred and heated at 80 °C for the time specified (Table [1] ) under a N₂ atmosphere. The reaction mixture was allowed to cool to r.t., poured into H₂O, extracted with CH₂Cl₂ and the organic extract dried over anhyd Na₂SO₄. The crude material obtained on solvent removal was purified by flash column chromatography on silica gel (hexane-CHCl_3- mixtures) to obtain the corresponding diaryl thienothiophenes. 4: Yield 70%; mp 300 °C (dec.); IR (KBr): 2922, 1588, 1512, 1417, 1340, 1106, 932, 850, 750, 737, 694, 524, 485 cm^-1; ¹H NMR (CDCl₃, 300 MHz): δ = 2.60 (s, 6 H, CH₃), 7.61 (d, J = 10.5 Hz, 4 H, ArH), 8.31 (d, J = 10.5 Hz, 4 H, ArH); Anal. Calcd for C₂₀H₁₄N₂O₄S₂: C, 58.54; H, 3.41; N, 6.83; S, 15.61. Found: C, 58.34; H, 3.63; N, 6.85; S, 15.49. 10: Yield 65%; mp 293-295 °C; IR (KBr): 3423, 2921, 1722, 1604, 1523, 1433, 1403, 1279, 1180, 1104, 1017, 965, 932, 850, 766, 700 cm^-1; ¹H NMR (CDCl₃, 300 MHz): δ = 2.57 (s, 6 H, -CH₃), 2.95 (s, 6 H, -OCH₃), 7.54 (d, J = 6 Hz, 4 H, ArH), 8.11 (d, J = 6 Hz, 4 H, ArH); Anal. Calcd for C₂₄H₂₀O₄S₂: C, 66.05; H, 4.60; S, 14.70. Found: C, 66.10; H, 4.52; S, 14.55. 12: Yield 71%; mp >320 °C; IR (KBr): 3070, 2921, 1655, 1510, 1485, 1432, 1360, 1301, 1269, 1088, 1035, 937, 897, 881, 790, 745, 672, 610, 592, 555, 463 cm^-1; ¹H NMR (CDCl₃, 300 MHz): δ = 2.57 (s, 6 H, CH₃), 2.67 (s, 6 H, -COCH₃), 7.29 (d, J = 3 Hz, 2 H, thiophene H), 7.60 (d, J = 3 Hz, 2 H, thiophene H); Anal. Calcd for C₂₀H₁₆O₂S₄: C, 57.69; H, 3.90; S, 31.22. Found: C, 57.54; H, 3.85; S, 31.02. 14: Yield 61%; mp 265-268 °C; IR (KBr): 2958, 2837, 1606, 1570, 1525, 1492, 1461, 1439, 1297, 1275, 1248, 1177, 1110, 1041, 1028, 926, 810, 825, 649, 628, 542, 517 cm^-1; ¹H NMR (CDCl₃, 300 MHz): δ = 2.20 (s, 6 H, -CH₃), 3.80 (s, 6 H, -OCH₃), 6.90 (d, J = 8.0 Hz, 4 H, ArH), 7.35 (d, J = 8.0 Hz, 4 H, ArH); Anal. Calcd for C₂₂H₂₀O₂S₂: C, 69.47; H, 5.26; S, 16.84. Found: C, 69.31; H, 5.20; S, 16.64. 18: Yield 47%; mp 308-311 °C; IR (KBr): 3086, 2916, 1440, 1418, 1382, 1216, 1158, 1117, 1045, 1034, 999, 961, 902, 863, 830, 809, 736, 725, 564 cm^-1; ¹H NMR (CDCl₃, 300 MHz): δ = 2.35 (s, 6 H, -CH₃), 2.50 (s, 6 H, -CH₃), 6.85 (s, 2 H, thienothiophene H), 7.30 (s, 4 H, ArH); Anal. Calcd for C₂₂H₁₈S₄: C, 64.40; H, 4.40; S, 31.22. Found: C, 64.28; H, 4.42; S, 31.02.

18

The in situ reduction of Pd²⁺ to Pd⁰ is conceivable via DMF and or tributylamine mediated processes. Tributylamine in turn could be generated via the Hoffmann elimination of the quarternary ammonium salt under the reaction conditions.

19 For a related mechanism proposed for Pd catalyzed arylations of 2-furfuraldehyde, see: McClure MS. Glover B. McSorley E. Millar A. Osterhout MH. Roschangar F. Org. Lett.  2001,  3:  1677 

20 That compound 12 containing an acetyl thiophene absorbs at lower energy (λ_max 367 nm) than the cyano- or ester-substituted benzene analogues 6 or 10 (λ_max 325-336 nm) may not be surprising on account of better charge delocalization available from a relatively less resonance-stabilized thiophene ring than from benzene. For discussion, see: Alobert ID. Marks TJ. Ratner MA. J. Am. Chem. Soc.  1997,  119:  6575 ; and references cited therein