Divergent synthesis of 3-substituted thieno[3,4-b]thiophene derivatives via hydroxy-based transformations

Abstract

Herein, we have developed the first Pd-catalytic method for the preparation of 3-hydroxythieno[3,4-b]thiophene-2-carboxylate, which can be widely utilized as the chemical building block for modular assembly of structurally diverse 3-substituted thieno[3,4-b]thiophene derivatives via hydroxy-based transformation. Furthermore, we have evaluated the effect on their photophysical properties of the introduction of different substitutions at the C3-position and prepared conjugated polymers bearing 3-substituted thieno[3,4-b]thiophene units. We demonstrated that the photoluminescence (PL) properties of thieno[3,4-b]thiophene-2-carboxylate can be efficiently modulated by introducing different functional groups at the C3-position.

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As is well recognized, thiophene-based conjugated molecules have played an indispensable role in the development of organic optoelectronics.¹ Among various thiophene building blocks, the thieno-[3,4-b]thiophene (TT) unit with functional groups has recently emerged as an extremely attractive electron-withdrawing building block in organic electronics.² In particular, thieno[3,4-b]thiophenes (TbTs) bearing a carboxyl group have been widely used in the development of donor and acceptor materials in organic solar cells (OSCs) represented by the PTB series family polymers and IDT-derived non-fullerene small molecules acceptors with state-of-the-art power conversion efficiencies (PCEs) (Scheme 1).^3–5 Thieno[3,4-b]thiophene (TbT) is an asymmetric fused bithiophene containing four functionalization positions, in which the proaromatic thiophene can effectively stabilize the quinoidal resonance of the aromatic thiophene, narrow the energy gap, and modulate the electronic structures of the resulting molecules.

Scheme 1 Representative donor and acceptor materials bearing thieno[3,4-b]thiophene-2-carboxylate units in organic solar cells.

Historically, synthesis of thieno[3,4-b]thiophenes (TbTs) bearing a carboxyl group involved: (1) Cu-mediated coupling between 4-bromothiophene-3-carbaldehyde and 2-mercaptoacetate (Scheme 2a).⁶ However, this method is suitable only for the preparation of 3-unsubsituted thieno[3,4-b]thiophenes; (2) the non-catalytic multi-step cyclization reaction from 3-substituted thiophene-2-carboxylate (Scheme 2b).⁷ Even though this method has the capacity to access 3-substituted thieno[3,4-b]thiophenes, it still suffers from disadvantages such as linear multi-step synthesis (more than 5 steps needs for each product), low yields, harsh reaction conditions, and limited substrate scopes. Thus, development of a methodology to access thieno[3,4-b]thiophenes with various substitution patterns at the 3-position in a rapid and modular manner from readily available precursors is highly appealing. Herein, we have developed the first Pd-catalytic method for the preparation of 3-hydroxythieno[3,4-b]thiophene-2-carboxylate from commercially available 4-bromothiophene-3-carboxylate and 2-mercaptoacetate (Scheme 2c), which has never been prepared before our study. We demonstrated that this 3-hydroxythieno[3,4-b]thiophene-2-carboxylate can be widely utilized as a chemical building block for modular assembly of structurally diverse 3-substituted thieno[3,4-b]thiophene derivatives via a wide range of hydroxy-based transformations. Moreover, we have evaluated the effect on their photophysical properties of the introduction of different substitutions at the C3-position and then developed a series of TT-based conjugated polymer donors.

Scheme 2 The conventional synthetic methods to access thieno[3,4-b]thiophene-2-carboxylates and our study.

In our preliminary study, the reaction of butyl 4-bromothiophene-3-carboxylate 1a with ethyl 2-mercaptoacetate 2a was examined under Cu-catalytic conditions. Unfortunately, the developed Cu-catalytic system for the preparation of 3-unsubstituted thiophene-2-carboxylate was not effective for this conversion (Table 1, entries 1–3). After an extensive screening such as different Pd⁰ sources, solvents, reaction times and ligands, we found that treatment of 1a (0.2 mmol) and 2a with Pd₂dba₃ (5 mol%), xantphos (10 mol%) in toluene (1 mL) at 120 °C for 24 h gave product 3a in 97% yield (Table 1, entry 4). Evaluation of different bases revealed that DIPEA was the best choice (entries 3–7). There is no reactivity at all in the absence of Pd catalyst (entry 8). Finally, we demonstrated that the product 3a can be smoothly cyclized to form the key intermediate 3-hydroxythieno[3,4-b]thiophene-2-carboxylate (entry 4) with 81% yield in the presence of KO^tBu in THF.

Table 1 Optimization of directed hydroarylation of unactivated alkene 1a with ethyl 2-mercaptoacetate 2a^a

Entry	Base	Catalyst	Ligand	Solvent	Temp. (°C)	Yield^b
a Reactions were carried out with [M] catalyst (10 mol%), ligand (10 mol%), base (1.5 equiv.), 1a (0.2 mmol), and ethyl 2-mercaptoacetate (2a, 0.4 mmol) in solvent (1 mL) for 24 h under a N2 atmosphere. b Yields were determined by isolation. N.R.: no reaction.
1	K2CO3	CuO	—	DMSO	60	N.R.
2	K2CO3	CuO	—	DMSO	140	N.R.
3	K2CO3	CuO	Phen	DMSO	140	N.R.
4	DIPEA	Pd 2 dba 3	Xantphos	Toluene	120	81
5	K2CO3	Pd2dba3	Xantphos	Toluene	120	61
6	KO^tBu	Pd2dba3	Xantphos	Toluene	120	21
7	NaO^tBu	Pd2dba3	Xantphos	Toluene	120	24
8	DIPEA	—	Xantphos	Toluene	120	N.R.

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As we proposed, the product 3-hydroxythieno[3,4-b]thiophene-2-carboxylate 4a obtained by the method described herein could provide access to structurally diverse 3-substituted thiophene-2-carboxylates by means of additional hydroxy-based transformations (Scheme 3).⁸ First, the hydroxy group of 4a was easily methylated to yield the 3-methoxythieno[3,4-b]thiophene-2-carboxylate 5 using methyl iodide as the methylation reagent. 3-Methoxythieno[3,4-b]thiophene-2-carboxylate 5 could further undergo bromination in the presence of NBS in DMF to yield compound 6 with 60% yield. Furthermore, the hydroxy group of 4a could also been smoothly transformed to –OTf in the presence of Tf₂O/pyridine, which is a versatile leaving group in a lot of different types of cross-coupling reactions.⁹ For example, the –OTf of 7 can couple with NaSCH₃ under Pd-catalytic conditions to produce compound 8 in 91% yield. In addition, the amination of product 7 with diphenylmethanimine in the presence of a Pd⁰ catalyst and K₃PO₄ in toluene also worked smoothly to afford the corresponding 9 in 86% yield. Product 7 could also undergo Suzuki coupling to yield 3-phenylthieno[3,4-b]thiophene-2-carboxylate 10 in 97% yield. Pd-Catalyzed Sonogashira coupling of product 7 and ethynylbenzene also smoothly occurred to access 3-alkynylthieno[3,4-b]thiophene-2-carboxylate 11 with 91% yield.

Scheme 3 Accessing structurally diverse 3-substituted thiophene-2-carboxylates by means of additional hydroxy-based transformations.

After development of the modular methodology to access diverse 3-substituted thieno[3,4-b]thiophene-2-carboxylates, we aimed to introduce these building blocks into conjugated polymers. Following the procedures developed, we synthesized the 3-methoxy and 3-methylthio TbT monomers with a branched alkyl chain to guarantee enough solubility of the polymers. The synthetic route is described in Scheme 4 (upper panel). Furthermore, we found that 4-bromo-6-formyl-3-substituted [3,4-b]thiophene-2-carboxylate 18 could been produced by regioselective monoformylation and sequential bromination, which can be further utilized in the development of new small molecule donors and acceptors.¹⁰ Then, a series of conjugated polymers were prepared by Stille coupling reactions of the TbT monomers and BDT-T or BDT,¹¹ namely P1, P2, P3, and P4 (Scheme 4, lower panel). Detailed synthetic routes and characterizations can be found in the Experimental section of the ESI.†

Scheme 4 The synthesis of new conjugated polymers bearing 3-methoxy or 3-methylthio TbT units.

We first evaluated the effect of the subsitution at the C3-position of thieno[3,4-b]thiophene-2-carboxylate on their photophysical properties. The absorption maxima, photoluminescence (PL) emission maxima, and PL quantum yields (Φ_f) of compounds TT, 5, 8, 9, 10 and 11 in both the solid state and CH₂Cl₂ solution are listed in Table 2, whereas the corresponding absorption, and emission spectra are depicted in Fig. 1 and Fig. S1 (ESI†). It is worth noting that all these compounds were stable to light, humidity and air. As shown in Fig. 1, the subsitution at the C3-position was observed to greatly influence the molecular absorption and fluorescence. By incorporation of functional groups into the C3-position, all of the absorption and emission peaks of these derivatives were obviously red-shifted and their PL efficiencies were also enhanced in comparison with the ethyl[3,4-b]thiophene-2-carboxylate (TT) in both the solid state and CH₂Cl₂ solution. This might stem from the restriction of intramolecular rotation (RIR) of the ester group at the C2-position and substitution at the C3-position. Fig. 1b and c reveal that the emission peaks of these monomers in thin films are different from their emissions in CH₂Cl₂. This likely indicates that these monomers involved different intermolecular interactions and molecular aggregation in the solid state and in the dilute solution state.

Table 2 Optical properties of 5, 8, 9, 10, 11 and TT in both the solid state and CH₂Cl₂ solution

Comp.	UV-Vis absorption		Emission
	λ ^solmax	λ ^filmmax	λ ^solmax	λ ^solidmax	Φ sol (%)
a Absolute quantum yield determined with an integrating sphere system. n.d. = not detected due to the weak emission intensity.
TT	338	352	357	n.d.	n.d.
5	352	388	409	499	3.42
8	368	400	426	447	0.71
9	369	400	442	462	88
10	352	359	429	440	9.64
11	378	397	430	478	6.5

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Fig. 1 (a) Normalized UV/Vis absorption spectra of 5, 8, 9, 10, 11 and ethyl[3,4-b]thiophene-2-carboxylate (TT) in a DCM solution; (b) normalized emission spectra in DCM; (c) normalized emission spectra in the solid state.

The optical properties of these conjugated polymers bearing 3-methoxy and 3-methylthio TbT units in solution and in thin films were then also characterized by UV-Vis absorption spectroscopy as shown in Fig. 2. The corresponding spectroscopic data are summarized in Table 3. In general, the absorption maxima of these polymers bearing 3-methoxy or 3-methylthio[3,4-b]thiophene-2-carboxylate in solution and in films showed blue-shifts compared with the related polymers, which did not have substitution at the C3-position.¹² This means that the steric hindrance of these substitutions at the C3-position likely disrupted the conjugation of the polymer chain. Thiomethylation of the polymers lead to larger blue-shifts in the absorption spectra compared to methoxylation of the polymers.^2,13 On the other hand, Fig. 2a and b reveal that the absorption peaks of the polymers in thin films are slightly red-shifted compared to their absorptions in CHCl₃. This likely indicates that the polymers form slightly stronger intermolecular interactions and molecular aggregation in the solid film than in the dilute solution state. Finally, gel permeation chromatography (GPC) was also measured to obtain the molecular weights. It showed average M_n of 14.4, 10.8, 21.2, and 12.3 kDa for P1, P2, P3, and P4, respectively. The polydispersity index (PDI) of these polymers was determined to be about 1.8–2.1. Notably, all the polymers are soluble in chloroform (CHCl₃), chlorobenzene (CB), and 1,2-dichlorobenzene (DCB).

Fig. 2 Normalized UV/Vis absorption spectra of P1, P2, P3, and P4 in a chloroform solution (a) and as a solid film (b).

Table 3 Optical of properties of P1, P2, P3, and P4 in both the film state and CHCl₃ solution

P	UV-Vis absorption			CV^c		GPC^d
	λ max	λ max	E ^optg ^b	LUMO	HOMO	M n (kD)	PDI
	Sol	Film	Film
a Determined from UV-Vis absorption spectroscopy in CHCl3 and as a thin film. b Estimated from the onset wavelength of the optical absorption: E^optg = 1240/λedge. c Vs. Ag/Ag^+ in acetonitrile solution with 0.1 M n-Bu4NPF6 as a supporting electrolyte. d Molecular weights measured using gel permeation chromatography (against polystyrene standards) in chlorobenzene at 80 °C.
P1	608	637	1.65	3.43	5.08	14.4	2.1
P2	619	660	1.56	3.47	5.03	10.8	1.9
P3	541	561	1.82	3.46	5.28	21.2	1.9
P4	549	572	1.80	3.46	5.26	12.3	2.1

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From the absorption onset in films, the optical bandgaps are evaluated to be 1.65, 1.56, 1.82, and 1.80 eV for P1, P2, P3, and P4, respectively. In general, the introduction of a thiomethyl group led to significant broader optical bandgaps. To further study the energy level and band gap of these polymers, electrochemical cyclic voltammetry (CV) has also been employed to measure their redox properties (Fig. S2 and S3 in the ESI†). On incorporation into the reductive onset potentials and the optical bandgaps, the LUMO/HOMO energy levels are estimated to be −3.43/−5.08 eV (P1), −3.47/−5.03 eV (P2), −3.46/−5.28 eV (P3), and −3.46/−5.26 eV (P4).

Conclusions

In conclusion, we have developed the first Pd-catalytic method for the preparation of 3-hydroxythieno[3,4-b]thiophene-2-carboxylate, which has never been prepared before our study. Furthermore, we demonstrated that 3-hydroxythieno[3,4-b]thiophene-2-carboxylate can be employed as a versatile chemical building block for modular assembly of structurally diverse 3-substituted thieno[3,4-b]thiophene derivatives via hydroxy-based transformations. Additionally, the optical and electrochemical properties of these 3-substituted thieno[3,4-b]thiophene derivatives were also investigated. The results revealed that the photoluminescence (PL) properties of thieno[3,4-b]thiophene-2-carboxylate can be efficiently modulated by introducing different functional groups at the C3-position. Finally, several conjugated polymers bearing 3-methoxy and 3-methylthio TbT units were also synthesized and characterized. The results indicated that we can efficiently tune the energy levels, the optical bandgaps and absorption spectra by introducing 3-substituted thieno[3,4-b]thiophene derivatives into polymers. The device fabrication, measurements and optimization are currently underway in our lab.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

We are grateful for the financial support from the National Natural Science Foundation of China (21871146 and 21602115), 1000-Talent Youth Program (020/BF180181), the Natural Science Foundation of Tianjin (18JCYBJC20400), the Fundamental Research Funds for the Central Universities and Nankai University.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c9qm00128j

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