Synlett 2014; 25(1): 93-96
DOI: 10.1055/s-0033-1340481
letter
© Georg Thieme Verlag Stuttgart · New York

Programmed Synthesis of Tetraarylthieno[3,2-b]thiophene by Site-Selective Suzuki Cross-Coupling Reactions of Tetrabromothieno[3,2-b]thiophene

Hien Nguyen*
a   Department of Chemistry, Hanoi National University of Education, 136 Xuanthuy Street, Caugiay District, Hanoi, Vietnam   Email: hiennguyenp@yahoo.com
,
Dung Xuan Nguyen
a   Department of Chemistry, Hanoi National University of Education, 136 Xuanthuy Street, Caugiay District, Hanoi, Vietnam   Email: hiennguyenp@yahoo.com
,
Thinh Quang Tran
a   Department of Chemistry, Hanoi National University of Education, 136 Xuanthuy Street, Caugiay District, Hanoi, Vietnam   Email: hiennguyenp@yahoo.com
,
Binh Ngoc Vo
a   Department of Chemistry, Hanoi National University of Education, 136 Xuanthuy Street, Caugiay District, Hanoi, Vietnam   Email: hiennguyenp@yahoo.com
,
Thao Huong Nguyen
a   Department of Chemistry, Hanoi National University of Education, 136 Xuanthuy Street, Caugiay District, Hanoi, Vietnam   Email: hiennguyenp@yahoo.com
,
Thi Minh Ha Vuong
b   Laboratoire de Chimie Moléculaire et Thio-organique, 6 Boulevard Maréchal Juin, 14050 Caen, France
,
Tung T. Dang*
c   Center d’elaboration de matériaux et d’etudes structurales, 29 rue Jeanne Marvig BP 94347, 31055 Toulouse Cedex 4, France   Email: dang.thanhtung@gmail.com
› Author Affiliations
Further Information

Publication History

Received: 08 July 2013

Accepted after revision: 02 October 2013

Publication Date:
04 December 2013 (online)

 


Abstract

Thieno[3,2-b]thiophene is a structural motif that can be found in many important organic materials. A number of mono-, di- and tetraarylthieno[3,2-b]thiophenes are reported herein.


#

Thieno[3,2-b]thiophene[2] is a structural motif present in a wide range of conducting polymers, p-type organic semiconductors, optoelectronics, nonlinear optics and electroluminescence materials. Thieno[3,2-b]thiophene can be used as a starting material in the synthesis of oligo-functionalized thieno[3,2-b]thiophenes, thienoacenes and helical thienoacenes, which are conducting polymers and chromophores.[2b] [3] In 2006, McCulloch et al. reported a liquid-crystalline semiconducting polymer (PBTTT) containing thieno[3,2-b]thiophene moieties with a very high charge-carrier mobility (Figure [1]).[4a] Recently, dinaphtho[2,3-b:2′,3′-f]thieno[3,2-b]thiophene (DNTT) and alkylated benzothieno[3,2-b][1]benzothiophene (C13BTBT) were shown to demonstrate a very high thin film mobility of 3.1 cm2/Vs and 17.2 cm2/Vs, respectively, in VD-OFETs.[4b] [c] Due to intermolecular sulfur–sulfur interactions, materials containing thieno[3,2-b]thiophene may increase the electronic transport between neighboring molecules. The introduction of substituents into the core structure of materials may change electronic properties, solubility as well as molecular packing.[2m] For tuning electronic properties, heterocycles have been widely functionalized by many methods, especially, by palladium(0)-catalyzed cross-coupling reactions.[5] It was previously shown that polyhalogenated heterocycles can be regio­selectively functionalized by palladium-catalyzed cross-coupling reactions at the carbon–halogen bonds adjacent to the heteroatom.[5] These were controlled by both electronic and steric factors. We recently reported the methodologies for functionalization of N-methyltetrabromo-pyrrole,[6] tetrabromothiophene,[6] tetrabromoselenophene[7] and tetrabromofuran,[8] based on site-selective palladium(0)-catalyzed Suzuki reactions.

Due to the importance of thieno[3,2-b]thiophene in materials science, we were interested in developing a sequential process for the functionalization of thieno[3,2-b]thiophene via site-selective palladium(0)-catalyzed ­Suzuki reactions of tetrabromothieno[3,2-b]thiophene with boronic acids. We report herein an efficient synthesis of mono-, di- and tetraarylthieno[3,2-b]thiophene using this strategy.

Zoom Image
Figure 1 Some organic materials containing thieno[3,2-b]thiophene
Zoom Image
Scheme 1 Synthesis of 2aj. Reagents and conditions: (i) 1 (1.0 equiv), Ar1B(OH)2 (1.2 equiv), Pd(PPh3)4 (5 mol%), K3PO4 (2.0 equiv), 110 °C, 4–6 h, solvent (see Table [1]).

The Suzuki–Miyaura reactions of 1 [9] (1.0 equiv) with a series of boronic acids (1.2 equiv) resulted in a site-selective formation of 2-aryl-3,5,6-tribromothieno[3,2-b]thiophenes 2aj [5] in 25–80% yields (Scheme [1] and Table [1]). The conditions used were optimized with regard to temperature, solvent, base additive, and water additive. Pd(PPh3)4 was found to be an efficient catalyst for the current reaction. Other well-known catalyst systems, such as Pd(OAc)2/X-Phos, resulted in lower yields of the desired products. All reactions were carried out at 90–110 °C in 4–6 hours.

Table 1 Synthesis of 2-Aryl-3,5,6-tribromothieno[3,2-b]thiophene 2aj

2

Ar1B(OH)2 used

Solvent/H2O (4:1)

Yielda (%)

a

PhB(OH)2

toluene

51

b

4-MeC6H4B(OH)2

toluene

50

c

3,5-Me2C6H3B(OH)2

toluene

80

d

4-t-BuC6H4B(OH)2

toluene

55

e

4-MeOC6H4B(OH)2

1,4-dioxaneb

25

f

β-NaphthylB(OH)2

toluene

42

g

3-EtOC6H4B(OH)2

toluene

55

h

4-F3CC6H4B(OH)2

toluene

68

i

acenaphthene-5-boronic acid

toluene

52

j

3-Me-4-MeOC6H3B(OH)2

toluene

50

a Isolated yields.

b See refs. [7b ]and [11].

The structures of the coupling products were established by spectroscopic methods. To confirm the site-selectivity of the Suzuki–Miyaura reactions, the structure of 2d was clearly characterized by X-ray crystal structure and 1H NMR and 13C NMR analysis (see Figure [2]). In agreement with previous reports,[7] [8] [10] the Suzuki reaction proceeded regioselectively due to the preference of the multibrominated heterocycles to undergo oxidative addition with Pd(0) at the most electron-deficient carbon atoms, for example C2 and/or C5 in the case of 2,3,5,6-tetrabromothieno[3,2-b]thiophene.[7a–c]

Zoom Image
Figure 2 X-ray crystal structure of 2d

The Suzuki–Miyaura reactions of 1 (1.0 equiv) with 2.2 equivalents of arylboronic acids afforded symmetrical 2,5-diaryl-3,6-dibromothieno[3,2-b]thiophenes 3ad [11] in 30–70% yield (Scheme [2] and Table [2]). The reactions again proceeded with very good site-selectivity as confirmed by 1H NMR and 13C NMR.

Zoom Image
Scheme 2 Synthesis of 3ad. Reagents and conditions: (i) 1 (1.0 equiv), Ar1B(OH)2 (2.2 equiv), Pd(Ph3P)4 (10 mol%), K3PO4 (4.0 equiv), toluene–H2O (4:1), 110 °C, 4–6 h.

Table 2 Synthesis of Symmetrical 2,5-Diaryl-3,6-dibromothieno[3,2-b]thiophenes 3ad

3

Ar1B(OH)2

Yielda (%)

a

PhB(OH)2

58

b

4-MeC6H4B(OH)2

70

c

3,5-Me2C6H3B(OH)2

42

d

4-t-BuC6H4B(OH)2

30

a Isolated yields.

Similarly, the unsymmetrically disubstituted 2,5-diaryl-3,6-dibromothieno[3,2-b]thiophenes 4ac could also be synthesized by our method with predictable selectivity (Scheme [3] and Table [3]).[12]

Zoom Image
Scheme 3 Synthesis of 4ac. Reagents and conditions: (i) 2 (1.0 equiv), Ar1B(OH)2 (1.2 equiv), Pd(PPh3)4 (10 mol%), K3PO4 (2.0 equiv), toluene–H2O (4:1), 110 °C, 4–6 h.

Table 3 Synthesis of Dissymmetrical 2,5-Diaryl-3,6-dibromothieno[3,2-b]thiophenes 4ac

4

ArB(OH)2

Yielda (%)

Ar1

Ar2

a

4-MeC6H4

3,5-Me2C6H3

38

b

3,5-Me2C6H3

Ph

46

c

4-t-BuC6H4

Ph

52

a Isolated yields.

Further coupling of 3b or 4c with 2.4 equivalents of arylboronic acids afforded tetraarylated thieno[3,2-b]thiophenes 5ac containing four identical aryl groups (Scheme [4] and Table [4]). Of note, attempts to prepare triarylated thieno[3,2-b]thiophenes from the dissymmetrical 2,5-diaryl-3,6-dibromothieno[3,2-b]thiophenes 4ac resulted in an inseparable mixture of 2,3,5- and 2,5,6-triarylated thieno[3,2-b]thiophenes.

Interestingly, 1 could also undergo site-selective Heck coupling with 4-methylstyrene,[13] and Sonogashira reaction with 4-methylphenylethyne (Scheme [5]).[14]

Zoom Image
Scheme 4 Synthesis of 5ac. Reagents and conditions: (i) 5a: 3b (1.0 equiv), Ar1B(OH)2 (2.4 equiv), Pd(PPh3)4 (10 mol%), K3PO4 (4.0 equiv), toluene–H2O (4:1), 110 °C, 24 h; 5b: 3 (1.0 equiv), Ar3B(OH)2 (2.4 equiv), Pd(PPh3)4 (10 mol%), K3PO4 (4.0 equiv), toluene–H2O (4:1), 110 °C, 24 h; (ii) 5c: 4 (1.0 equiv), Ar3B(OH)2 (2.4 equiv), Pd(PPh3)4 (10 mol%), K3PO4 (4.0 equiv), toluene–H2O (4:1), 110 °C, 24 h.

Table 4 Synthesis of Tetraarylthieno[3,2-b]thiophene 5ac

5

ArB(OH)2

Yielda (%)

Ar1

Ar2

Ar3

a

4-MeC6H4

4-MeC6H4

30

b

4-MeC6H4

Ph

35

c

4-t-BuC6H4

Ph

4-MeC6H4

25

a Isolated yields.

Zoom Image
Scheme 5 Synthesis of 6 and 7. Reagents and conditions: (i) 6: 1 (1.0 equiv), 4-methylstyrene (10.0 equiv), Pd(OAc)2 (10 mol%), (Cy)3P (20 mol%), DMF, 90 °C, 6 h; (ii) 7: 1 (1.0 equiv), arylethyne (1.2 equiv), Pd(OAc)2 (10 mol%), Ph3P (20 mol%), CuI (20 mol%), DMF–Et3N (1:1), 75 °C, 2.5 h.

In conclusion, we have showed that the Suzuki–Miyaura reactions of polybromothieno[3,2-b]thiophene can proceed with predictable site-selectivity, preferably at C2 and C5.[15] Controlled synthesis of 2-aryl-3,5,6-tribromothieno[3,2-b]thiophenes, 2,5-diaryl-3,6-dibromothieno[3,2-b]thiophenes, and tetraarylated thieno[3,2-b]thiophenes could thus be achieved. Similar regioselectivity was observed for the Heck and Sonogashira couplings of 2,3,5,6-tetrabromothieno[3,2-b]thiophenes. Applications of this coupling strategy in the synthesis of materials incorporating thieno[3,2-b]thiophene moieties are now underway in our laboratory, and will be reported in due course.


#

Acknowledgment

This research was funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) under the grant number 104.01-2012.26.

  • References and Notes

  • 1 Present address: Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France.�
    • 2a Litvinov VP, Goldfarb YA. L In Advances in Heterocyclic Chemistry . Vol. 19. Katritzky AR, Boulton AJ. Academic Press; San Diego: 1976
    • 2b Mishra A, Ma C.-Q, Bäuerle P. Chem. Rev. 2009; 109: 1141
    • 2c Liu Y, Liu Q, Zhang X, Ai L, Wang Y, Peng R, Ge Z. New J. Chem. 2013; 37: 1189
    • 2d Hergue N, Frere P, Roncali J. Org. Biomol. Chem. 2011; 9: 588
    • 2e Leriche P, Raimundo J.-M, Turbiez M, Monroche V, Allain M, Sauvage F.-X, Roncali J, Frere P, Skabara PJ. J. Mater. Chem. 2003; 13: 1324
    • 2f Ahmed MO, Wang C, Keg P, Pisula W, Lam Y.-M, Ong BS, Ng S.-C, Chen Z.-K, Mhaisalkar SG. J. Mater. Chem. 2009; 19: 3449
    • 2g Cheng Y.-J, Chen C.-H, Lin T.-Y, Hsu C.-S. Chem. Asian J. 2012; 7: 818
    • 2h Burkhardt SE, Conte S, Rodriguez-Calero GG, Lowe MA, Qian H, Zhou W, Gao J, Hennig RG, Abruna HD. J. Mater. Chem. 2011; 21: 9553
    • 2i Yamamoto T, Nishimura T, Mori T, Miyazaki E, Osaka I, Takimiya K. Org. Lett. 2012; 14: 4914
    • 2j Yamaguchi Y, Maruya Y, Katagiri H, Nakayama K.-I, Ohba Y. Org. Lett. 2012; 14: 2316
    • 2k Huang J, Luo H, Wang L, Guo Y, Zhang W, Chen H, Zhu M, Liu Y, Yu G. Org. Lett. 2012; 14: 3300
    • 2l Henson ZB, Müllen K, Bazan GC. Nature Chem. 2012; 4: 699
    • 2m Mei J, Diao Y, Appleton AL, Fang AL, Bao Z. J. Am. Chem. Soc. 2013; 135: 6724
  • 3 Liu Y, Sun X, Di C.-A, Liu Y, Du C, Lu K, Ye S, Yu G. Chem. Asian J. 2010; 5: 1550
    • 4a McCulloch I, Heeney M, Bailey C, Genevicius K, MacDonald I, Shkunov M, Sparrowe D, Tierney S, Wagner R, Zhang W, Chabinyc ML, Kline RJ, McGehee MD, Toney MF. Nature Mater. 2006; 5: 328
    • 4b Niimi K, Shinamura S, Osaka I, Miyazaki E, Takimiya K. J. Am. Chem. Soc. 2011; 133: 8732
    • 4c Ebata H, Izawa T, Miyazaki E, Takimiya K, Ikeda M, Kuwabara H, Yui T. J. Am. Chem. Soc. 2007; 129: 15732
    • 5a Schröter S, Stock C, Bach T. Tetrahedron 2005; 61: 2245
    • 5b Bellina F, Rossi R. Adv. Synth. Catal. 2010; 352: 8
    • 6a Dang TT, Ahmad R, Dang TT, Reinke H, Langer P. Tetrahedron Lett. 2008; 49: 1698
    • 6b Ullah F, Dang TT, Heinicke J, Villinger A, Langer P. Synlett 2009; 838
    • 7a Dang TT, Rasool N, Dang TT, Reinke H, Langer P. Tetrahedron Lett. 2007; 48: 845
    • 7b Tung DT, Tuan DT, Rasool N, Villinger A, Reinke H, Fischer C, Langer P. Adv. Synth. Catal. 2009; 351: 1595
    • 7c Ehlers P, Tung DT, Patonay T, Villinger A, Langer P. Eur. J. Org. Chem. 2013; 10: 2000
    • 7d Tuan DT, Rasool N, Tung DT, Reinke H, Langer P. Tetrahedron Lett. 2007; 48: 845
  • 8 Tung DT, Villinger A, Langer P. Adv. Synth. Catal. 2008; 350: 2109
  • 9 Fuller SL, Iddon B, Smith AK. J. Chem. Soc., Perkin Trans. 1 1997; 3465
  • 10 Hussain M, Khera RA, Hung NT, Langer P. Org. Biomol. Chem. 2011; 9: 370
  • 11 General Procedure for the Synthesis of 2-Aryl-3,5,6-tribromothieno[3,2-b]thiophene 2aj: Toluene was degassed by exchanging between vacuum and a stream of argon (3 ×). 2,3,5,6-Tetrabromothieno[3,2-b]thiophene (1.0 equiv) and Pd(Ph3P)4 (0.05–0.10 equiv) were dissolved in this degassed toluene (4 mL) at 60–70 °C. To the obtained solution H2O (1 mL), K3PO4 (2.0 equiv), and arylboronic acid (1.2 equiv) were added. The reaction was vigorously stirred under argon atmosphere at 110 °C until TLC (100% hexane) showed the complete consumption of the starting material. The reaction mixture was filtered to remove insoluble particles. The filtrate was washed several times with H2O, dried over Na2SO4 and concentrated under reduced pressure by rotary evaporation. The residue was purified by SiO2 column chromatography (100% hexane) to give the product as a white solid. In case of alkoxyphenyl boronic acid, 1,4-dioxane was used instead of toluene (ref. 6b). In fact, toluene–H2O gave the same result. 2,3,6-Tribromo-5-phenylthieno[3,2-b]thiophene (2a): Starting from 1 (230 mg, 0.5 mmol) and phenylboronic acid (74 mg, 0.6 mmol), 2a was isolated (191 mg, 51%) as white crystals; mp 132–133 °C. 1H NMR (500 MHz, CDCl3): δ = 7.68 (m, 2 H, Ar), 7.45 (m, 3 H, Ar). 13C NMR (500 MHz, CDCl3): δ = 99.8, 106.9, 112.5, 128.8, 128.9, 129.0, 132.4, 136.4, 139.8. IR (KBr): 3083 (m), 2929 (s), 2905 (m), 1658 (m), 1610 (m), 1582 (m), 743 (s), 684 (s), 588 (m) cm–1. HRMS (EI, 70 eV): m/z (M+, [79Br,79Br,79Br]) calcd for C12H5Br3S2: 449.7383; found: 449.7392.
  • 12 General Procedure for the Synthesis of 2,5-Diaryl-3,6-dibromothieno[3,2-b]thiophenes 4ac: Toluene was degassed by exchanging between vacuum and a stream of argon (3 ×). 2-Ar1-3,5,6-tribromothieno[3,2-b]thiophene 2 (1.0 equiv) was dissolved in this degassed toluene (4 mL) at r.t. To the obtained solution were added H2O (1 mL), K3PO4 (2.0 equiv), Pd(Ph3P)4 (0.10 equiv) and an Ar2boronic acid (1.2 equiv). The reaction was vigorously stirred under argon atmosphere at 110 °C until TLC (100% hexane) showed the complete consumption of the starting material. The reaction was quenched with H2O and the mixture was extracted with EtOAc (3 ×). The extracts were collected, dried over Na2SO4 and concentrated under reduced pressure by rotary evaporation. The residue was purified by SiO2 column chromatography (100% hexane → 2% EtOAc in hexane) or by recrystallization from hot toluene to give the product as white crystals. 3,6-Dibromo-2-(3,5-dimethylphenyl)-5-phenylthieno[3,2-b]-thiophene (4b): Starting from 2c (115 mg, 0.25 mmol) and phenylboronic acid (36.6 mg, 0.3 mmol), 4b was isolated (54.7 mg, 46%) as a white solid by SiO2 column chromatography (100% hexane); mp 185–186 °C. 1H NMR (500 MHz, CDCl3): δ = 7.72 (m, 2 H, Ar), 7.48 (m, 2 H, Ar), 7.42 (m, 1 H, Ar), 7.33 (s, 2 H, Ar), 7.06 (s, 1 H, Ar), 2.40 (s, 6 H, 2 × Me). 13C NMR (500 MHz, CDCl3): δ = 21.3 (Me), 99.8, 100.1, 126.8, 128.7, 128.8, 129.1, 130.5, 132.7, 133.0, 138.4, 138.7, 138.8, 139.2, 139.9. IR (KBr): 3027 (w), 2920 (m), 2870 (m), 1653 (m), 1598 (m), 746 (m) cm–1. HRMS (EI, 70 eV): m/z (M+, [79Br,79Br]) calcd for C20H14Br2S2: 475.8904; found: 475.8916.
  • 13 Synthesis of 2-(4-Methylstyryl)-3,5,6-tribromothieno[3,2-b]thiophene (6): DMF (4 mL) was saturated with argon by exchanging between vacuum and a stream of argon (3 ×). Pd(OAc)2 (2.8 mg, 0.0125 mmol, 0.1 equiv) and P(Cy)3 (7.0 mg, 0.025mmol, 0.2 equiv) were dissolved in this argon-saturated solvent. The brownish yellow solution was stirred at r.t. for further 30 min to produce the catalyst. 2,3,5,6-Tetrabromothieno[3,2-b]thiophene (0.57 mg, 0.125 mmol, 1.0 equiv), Na2CO3 (79.5 mg, 0.75 mmol, 6.0 equiv) and 4-methylstyrene (295.5 mg, 12.5 mmol, 10.0 equiv) were added to the solution of the catalyst under a stream of argon. The reaction solution was heated at 90 °C in 5.5 h under argon atmosphere. The progress of the reaction was monitored by TLC (100% hexane). Besides the monoalkenyl substituted derivative, small amounts of di- and trialkenyl-substituted derivatives were also observed. When the starting material was completely consumed as indicated by TLC, the brownish mixture was allowed to cool to r.t., filtered through Celite to remove the brown precipitate. The filtrate was extracted several times with EtOAc, washed with H2O (3 ×) and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure by rotary evaporation and the residue was purified by SiO2 column chromatography (100% hexane) to give the monoalkenylated 2,3,5,6-tetrabromothieno[3,2-b]thiophene as a yellow solid (76.1 mg, 42%); mp 126–127 °C. 1H NMR (500 MHz, CDCl3): δ = 7.40 (d, J = 8.0 Hz, 2 H, Ar), 7.20 (d, J = 16.5 Hz, 1 H), 7.17 (d, J = 8.5 Hz, 2 H, Ar), 6.98 (d, J = 16.0 Hz, 1 H), 2.36 (s, 3 H, Me). 13C NMR (500 MHz, CDCl3): δ = 139.4, 139.1, 138.7, 135.1, 133.4, 131.2, 129.6, 126.7, 118.9, 112.5, 107.2, 102.5, 21.4.
  • 14 General Procedure for the Synthesis of 2-Alkynyl-3,5,6-tribromothieno[3,2-b]thiophene 7: A mixture (1:1) of diisopropylamine and THF was saturated with argon by exchanging between vacuum and a stream of argon (3 ×). 2,3,5,6-Tetrabromothieno[3,2-b]thiophene (1.0 equiv), Pd(OAc)2 (0.1 equiv), Ph3P (0.2 equiv) and CuI (0.2 equiv) were added to this argon-saturated solution. The suspension was heated to 75 °C while vigorously stirred until it became homogeneous. To the obtained pale yellow mixture, a solution of arylacetylene (1.2 equiv) in argon-saturated THF (1.0 mL) was added dropwise in 30 min. The reaction mixture was heated at 75 °C for 3–6 h. The pale yellow reaction mixture turned reddish brown when the reaction completed as indicated by TLC (100% hexane). The reaction mixture was adsorbed on silica gel, dried under reduced pressure and purified by SiO2 column chromatography to furnish the monoalkynated derivative. Besides the desired product, a significant amount of the symmetric diynes resulting from the homocoupling reaction of the alkynes was separated. All attempts to reduce this by-product were not successful. 2-(4-Methylphenylethynyl)-3,5,6-tribromothieno[3,2-b]thiophene (7a): Starting from 1 (0.57 mg, 0.125 mmol) and 4-ethynyltoluene (17.4 mg, 0.15 mmol), 7 was isolated (32 mg, yield 52%) as a white solid; mp 193–194 °C. 1H NMR (500 MHz, CDCl3): δ = 7.46 (d, J = 8.0 Hz, 2 H, Ar), 7.18 (d, J = 8.0 Hz, 2 H, Ar), 2.38 (s, 3 H, Me). 13C NMR (500 MHz, CDCl3): δ = 139.6, 138.0, 131.7, 131.5, 129.3, 119.0, 114.8, 107.9, 107.1, 99.9, 80.5, 21.6.
  • 15 CCDC 971825 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.�

  • References and Notes

  • 1 Present address: Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France.�
    • 2a Litvinov VP, Goldfarb YA. L In Advances in Heterocyclic Chemistry . Vol. 19. Katritzky AR, Boulton AJ. Academic Press; San Diego: 1976
    • 2b Mishra A, Ma C.-Q, Bäuerle P. Chem. Rev. 2009; 109: 1141
    • 2c Liu Y, Liu Q, Zhang X, Ai L, Wang Y, Peng R, Ge Z. New J. Chem. 2013; 37: 1189
    • 2d Hergue N, Frere P, Roncali J. Org. Biomol. Chem. 2011; 9: 588
    • 2e Leriche P, Raimundo J.-M, Turbiez M, Monroche V, Allain M, Sauvage F.-X, Roncali J, Frere P, Skabara PJ. J. Mater. Chem. 2003; 13: 1324
    • 2f Ahmed MO, Wang C, Keg P, Pisula W, Lam Y.-M, Ong BS, Ng S.-C, Chen Z.-K, Mhaisalkar SG. J. Mater. Chem. 2009; 19: 3449
    • 2g Cheng Y.-J, Chen C.-H, Lin T.-Y, Hsu C.-S. Chem. Asian J. 2012; 7: 818
    • 2h Burkhardt SE, Conte S, Rodriguez-Calero GG, Lowe MA, Qian H, Zhou W, Gao J, Hennig RG, Abruna HD. J. Mater. Chem. 2011; 21: 9553
    • 2i Yamamoto T, Nishimura T, Mori T, Miyazaki E, Osaka I, Takimiya K. Org. Lett. 2012; 14: 4914
    • 2j Yamaguchi Y, Maruya Y, Katagiri H, Nakayama K.-I, Ohba Y. Org. Lett. 2012; 14: 2316
    • 2k Huang J, Luo H, Wang L, Guo Y, Zhang W, Chen H, Zhu M, Liu Y, Yu G. Org. Lett. 2012; 14: 3300
    • 2l Henson ZB, Müllen K, Bazan GC. Nature Chem. 2012; 4: 699
    • 2m Mei J, Diao Y, Appleton AL, Fang AL, Bao Z. J. Am. Chem. Soc. 2013; 135: 6724
  • 3 Liu Y, Sun X, Di C.-A, Liu Y, Du C, Lu K, Ye S, Yu G. Chem. Asian J. 2010; 5: 1550
    • 4a McCulloch I, Heeney M, Bailey C, Genevicius K, MacDonald I, Shkunov M, Sparrowe D, Tierney S, Wagner R, Zhang W, Chabinyc ML, Kline RJ, McGehee MD, Toney MF. Nature Mater. 2006; 5: 328
    • 4b Niimi K, Shinamura S, Osaka I, Miyazaki E, Takimiya K. J. Am. Chem. Soc. 2011; 133: 8732
    • 4c Ebata H, Izawa T, Miyazaki E, Takimiya K, Ikeda M, Kuwabara H, Yui T. J. Am. Chem. Soc. 2007; 129: 15732
    • 5a Schröter S, Stock C, Bach T. Tetrahedron 2005; 61: 2245
    • 5b Bellina F, Rossi R. Adv. Synth. Catal. 2010; 352: 8
    • 6a Dang TT, Ahmad R, Dang TT, Reinke H, Langer P. Tetrahedron Lett. 2008; 49: 1698
    • 6b Ullah F, Dang TT, Heinicke J, Villinger A, Langer P. Synlett 2009; 838
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    • 7c Ehlers P, Tung DT, Patonay T, Villinger A, Langer P. Eur. J. Org. Chem. 2013; 10: 2000
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  • 11 General Procedure for the Synthesis of 2-Aryl-3,5,6-tribromothieno[3,2-b]thiophene 2aj: Toluene was degassed by exchanging between vacuum and a stream of argon (3 ×). 2,3,5,6-Tetrabromothieno[3,2-b]thiophene (1.0 equiv) and Pd(Ph3P)4 (0.05–0.10 equiv) were dissolved in this degassed toluene (4 mL) at 60–70 °C. To the obtained solution H2O (1 mL), K3PO4 (2.0 equiv), and arylboronic acid (1.2 equiv) were added. The reaction was vigorously stirred under argon atmosphere at 110 °C until TLC (100% hexane) showed the complete consumption of the starting material. The reaction mixture was filtered to remove insoluble particles. The filtrate was washed several times with H2O, dried over Na2SO4 and concentrated under reduced pressure by rotary evaporation. The residue was purified by SiO2 column chromatography (100% hexane) to give the product as a white solid. In case of alkoxyphenyl boronic acid, 1,4-dioxane was used instead of toluene (ref. 6b). In fact, toluene–H2O gave the same result. 2,3,6-Tribromo-5-phenylthieno[3,2-b]thiophene (2a): Starting from 1 (230 mg, 0.5 mmol) and phenylboronic acid (74 mg, 0.6 mmol), 2a was isolated (191 mg, 51%) as white crystals; mp 132–133 °C. 1H NMR (500 MHz, CDCl3): δ = 7.68 (m, 2 H, Ar), 7.45 (m, 3 H, Ar). 13C NMR (500 MHz, CDCl3): δ = 99.8, 106.9, 112.5, 128.8, 128.9, 129.0, 132.4, 136.4, 139.8. IR (KBr): 3083 (m), 2929 (s), 2905 (m), 1658 (m), 1610 (m), 1582 (m), 743 (s), 684 (s), 588 (m) cm–1. HRMS (EI, 70 eV): m/z (M+, [79Br,79Br,79Br]) calcd for C12H5Br3S2: 449.7383; found: 449.7392.
  • 12 General Procedure for the Synthesis of 2,5-Diaryl-3,6-dibromothieno[3,2-b]thiophenes 4ac: Toluene was degassed by exchanging between vacuum and a stream of argon (3 ×). 2-Ar1-3,5,6-tribromothieno[3,2-b]thiophene 2 (1.0 equiv) was dissolved in this degassed toluene (4 mL) at r.t. To the obtained solution were added H2O (1 mL), K3PO4 (2.0 equiv), Pd(Ph3P)4 (0.10 equiv) and an Ar2boronic acid (1.2 equiv). The reaction was vigorously stirred under argon atmosphere at 110 °C until TLC (100% hexane) showed the complete consumption of the starting material. The reaction was quenched with H2O and the mixture was extracted with EtOAc (3 ×). The extracts were collected, dried over Na2SO4 and concentrated under reduced pressure by rotary evaporation. The residue was purified by SiO2 column chromatography (100% hexane → 2% EtOAc in hexane) or by recrystallization from hot toluene to give the product as white crystals. 3,6-Dibromo-2-(3,5-dimethylphenyl)-5-phenylthieno[3,2-b]-thiophene (4b): Starting from 2c (115 mg, 0.25 mmol) and phenylboronic acid (36.6 mg, 0.3 mmol), 4b was isolated (54.7 mg, 46%) as a white solid by SiO2 column chromatography (100% hexane); mp 185–186 °C. 1H NMR (500 MHz, CDCl3): δ = 7.72 (m, 2 H, Ar), 7.48 (m, 2 H, Ar), 7.42 (m, 1 H, Ar), 7.33 (s, 2 H, Ar), 7.06 (s, 1 H, Ar), 2.40 (s, 6 H, 2 × Me). 13C NMR (500 MHz, CDCl3): δ = 21.3 (Me), 99.8, 100.1, 126.8, 128.7, 128.8, 129.1, 130.5, 132.7, 133.0, 138.4, 138.7, 138.8, 139.2, 139.9. IR (KBr): 3027 (w), 2920 (m), 2870 (m), 1653 (m), 1598 (m), 746 (m) cm–1. HRMS (EI, 70 eV): m/z (M+, [79Br,79Br]) calcd for C20H14Br2S2: 475.8904; found: 475.8916.
  • 13 Synthesis of 2-(4-Methylstyryl)-3,5,6-tribromothieno[3,2-b]thiophene (6): DMF (4 mL) was saturated with argon by exchanging between vacuum and a stream of argon (3 ×). Pd(OAc)2 (2.8 mg, 0.0125 mmol, 0.1 equiv) and P(Cy)3 (7.0 mg, 0.025mmol, 0.2 equiv) were dissolved in this argon-saturated solvent. The brownish yellow solution was stirred at r.t. for further 30 min to produce the catalyst. 2,3,5,6-Tetrabromothieno[3,2-b]thiophene (0.57 mg, 0.125 mmol, 1.0 equiv), Na2CO3 (79.5 mg, 0.75 mmol, 6.0 equiv) and 4-methylstyrene (295.5 mg, 12.5 mmol, 10.0 equiv) were added to the solution of the catalyst under a stream of argon. The reaction solution was heated at 90 °C in 5.5 h under argon atmosphere. The progress of the reaction was monitored by TLC (100% hexane). Besides the monoalkenyl substituted derivative, small amounts of di- and trialkenyl-substituted derivatives were also observed. When the starting material was completely consumed as indicated by TLC, the brownish mixture was allowed to cool to r.t., filtered through Celite to remove the brown precipitate. The filtrate was extracted several times with EtOAc, washed with H2O (3 ×) and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure by rotary evaporation and the residue was purified by SiO2 column chromatography (100% hexane) to give the monoalkenylated 2,3,5,6-tetrabromothieno[3,2-b]thiophene as a yellow solid (76.1 mg, 42%); mp 126–127 °C. 1H NMR (500 MHz, CDCl3): δ = 7.40 (d, J = 8.0 Hz, 2 H, Ar), 7.20 (d, J = 16.5 Hz, 1 H), 7.17 (d, J = 8.5 Hz, 2 H, Ar), 6.98 (d, J = 16.0 Hz, 1 H), 2.36 (s, 3 H, Me). 13C NMR (500 MHz, CDCl3): δ = 139.4, 139.1, 138.7, 135.1, 133.4, 131.2, 129.6, 126.7, 118.9, 112.5, 107.2, 102.5, 21.4.
  • 14 General Procedure for the Synthesis of 2-Alkynyl-3,5,6-tribromothieno[3,2-b]thiophene 7: A mixture (1:1) of diisopropylamine and THF was saturated with argon by exchanging between vacuum and a stream of argon (3 ×). 2,3,5,6-Tetrabromothieno[3,2-b]thiophene (1.0 equiv), Pd(OAc)2 (0.1 equiv), Ph3P (0.2 equiv) and CuI (0.2 equiv) were added to this argon-saturated solution. The suspension was heated to 75 °C while vigorously stirred until it became homogeneous. To the obtained pale yellow mixture, a solution of arylacetylene (1.2 equiv) in argon-saturated THF (1.0 mL) was added dropwise in 30 min. The reaction mixture was heated at 75 °C for 3–6 h. The pale yellow reaction mixture turned reddish brown when the reaction completed as indicated by TLC (100% hexane). The reaction mixture was adsorbed on silica gel, dried under reduced pressure and purified by SiO2 column chromatography to furnish the monoalkynated derivative. Besides the desired product, a significant amount of the symmetric diynes resulting from the homocoupling reaction of the alkynes was separated. All attempts to reduce this by-product were not successful. 2-(4-Methylphenylethynyl)-3,5,6-tribromothieno[3,2-b]thiophene (7a): Starting from 1 (0.57 mg, 0.125 mmol) and 4-ethynyltoluene (17.4 mg, 0.15 mmol), 7 was isolated (32 mg, yield 52%) as a white solid; mp 193–194 °C. 1H NMR (500 MHz, CDCl3): δ = 7.46 (d, J = 8.0 Hz, 2 H, Ar), 7.18 (d, J = 8.0 Hz, 2 H, Ar), 2.38 (s, 3 H, Me). 13C NMR (500 MHz, CDCl3): δ = 139.6, 138.0, 131.7, 131.5, 129.3, 119.0, 114.8, 107.9, 107.1, 99.9, 80.5, 21.6.
  • 15 CCDC 971825 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.�

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Figure 1 Some organic materials containing thieno[3,2-b]thiophene
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Scheme 1 Synthesis of 2aj. Reagents and conditions: (i) 1 (1.0 equiv), Ar1B(OH)2 (1.2 equiv), Pd(PPh3)4 (5 mol%), K3PO4 (2.0 equiv), 110 °C, 4–6 h, solvent (see Table [1]).
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Figure 2 X-ray crystal structure of 2d
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Scheme 2 Synthesis of 3ad. Reagents and conditions: (i) 1 (1.0 equiv), Ar1B(OH)2 (2.2 equiv), Pd(Ph3P)4 (10 mol%), K3PO4 (4.0 equiv), toluene–H2O (4:1), 110 °C, 4–6 h.
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Scheme 3 Synthesis of 4ac. Reagents and conditions: (i) 2 (1.0 equiv), Ar1B(OH)2 (1.2 equiv), Pd(PPh3)4 (10 mol%), K3PO4 (2.0 equiv), toluene–H2O (4:1), 110 °C, 4–6 h.
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Scheme 4 Synthesis of 5ac. Reagents and conditions: (i) 5a: 3b (1.0 equiv), Ar1B(OH)2 (2.4 equiv), Pd(PPh3)4 (10 mol%), K3PO4 (4.0 equiv), toluene–H2O (4:1), 110 °C, 24 h; 5b: 3 (1.0 equiv), Ar3B(OH)2 (2.4 equiv), Pd(PPh3)4 (10 mol%), K3PO4 (4.0 equiv), toluene–H2O (4:1), 110 °C, 24 h; (ii) 5c: 4 (1.0 equiv), Ar3B(OH)2 (2.4 equiv), Pd(PPh3)4 (10 mol%), K3PO4 (4.0 equiv), toluene–H2O (4:1), 110 °C, 24 h.
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Scheme 5 Synthesis of 6 and 7. Reagents and conditions: (i) 6: 1 (1.0 equiv), 4-methylstyrene (10.0 equiv), Pd(OAc)2 (10 mol%), (Cy)3P (20 mol%), DMF, 90 °C, 6 h; (ii) 7: 1 (1.0 equiv), arylethyne (1.2 equiv), Pd(OAc)2 (10 mol%), Ph3P (20 mol%), CuI (20 mol%), DMF–Et3N (1:1), 75 °C, 2.5 h.