Direct arylation of dithienylperfluorocyclopentenes via palladium-catalysed C–H bond activation: a simpler access to photoswitches

Abstract

The palladium-catalysed direct arylation of dithienylperfluorocyclopentene (DTE) derivatives proceeds in moderate to high yields with a variety of aryl bromides in the presence of 5 mol% Pd(OAc)₂/dppb as the catalyst, and KOAc as the base. The use of cyclopentyl methyl ether as the solvent was found to be crucial to avoid the decomposition of the reactants and products. The reaction proceeds regioselectively at C5 of thiophenes, and tolerates various substituents such as formyl, acetyl, ester, nitrile or nitro on the aryl bromide. Therefore, this method allows a straightforward modulation of the electron density distribution on DTE derivatives.

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Introduction

The palladium-catalysed direct arylation of heteroaromatics has recently emerged as a very powerful method for the preparation of arylated heteroaromatics including thiophenes.^1–4 However, there are still limitations for these reactions in terms of substrate scope. The presence of acetyl, amino, bromide, ester, formyl, nitrile, methylalcohol or trimethylsilyl as the functional groups on the thiophenes has largely described.^5a–n On the other hand, the arylation of dithienylperfluorocyclopentene (DTE) derivatives has attracted less attention.^5o

Among various photochromic systems,⁶ DTE derivatives have particularly attracted increased interest for their excellent stability and fatigue-resistance properties making them important building blocks for the synthesis of photoswitching materials (Fig. 1).⁷

Fig. 1 Photochromism of dithienylperfluorocyclopentene.

Arylated DTE can be prepared by Suzuki–Miyaura or Negishi couplings (Scheme 1, top).^8,9 However, such syntheses are time consuming and the yields are often modest. Therefore, to overcome these limitations, a straightforward and selective method for the functionalisation of DTE derivatives is highly desirable.

Scheme 1

Very recently, it has been reported that dithienylperfluorocyclopentene 1 can be easily obtained in high yield by Suzuki–Miyaura cross-coupling of 2-methyl-3-thienylboronic acid with 1,2-dichlorohexafluorocyclopentene (Scheme 2).¹⁰ It should be noted that this latter compound is commercially available at an affordable cost allowing the synthesis of 1 on a large scale.

Scheme 2

Therefore, the palladium-catalysed direct arylation of 1 or its derivatives for access to arylated DTE derivatives would present considerable advantages (Scheme 1, bottom). It would allow us to reduce the number of steps to prepare these compounds. Moreover, lower amounts of wastes would be produced. In addition, such couplings are expected to present a better functional group tolerance, which would allow a straightforward modification of the nature of the aryl group and hence of the photochromic properties of the resulting DTE derivatives.

Results and discussion

We now report (i) conditions for the palladium-catalysed direct regioselective mono- or diarylation of DTE derivatives with (hetero)aryl bromides using a cheap base and an air stable catalyst, (ii) the formation of a wide variety of diarylated derivatives of DTE with either two different or two identical aryl groups, (iii) that this method tolerates several functional groups.

Keeping in mind the conditions used for the direct arylation in our previous works, we examined the influence of the nature of the solvent, catalyst precursor and reaction temperature for the coupling of 4-bromobenzonitrile with 2 (Scheme 3) using KOAc as a base.^3,5k–m We observed that, in the course of this reaction, the use of DMAc as the solvent and 2–5 mol% PdCl(C₃H₅)(dppb) [dppb: 1,4-bis(diphenylphosphino)butane)], Pd(OAc)₂ or Pd(OAc)₂/dppb as the catalysts at 140 °C did not result in the formation of the target product 3a. Instead, decomposition of 2 was observed. Similar results were obtained at 130 °C. On the other hand, the use of cyclopentyl methyl ether (CPME) as the solvent for this reaction, using 5 mol% Pd(OAc)₂ as the palladium source and 5 mol% dppb as the ligand at 140 °C, afforded cleanly the desired arylated product 3a in 69% yield. No formation of other regioisomers or diarylated thiophenes was detected. We had previously observed that cyclopentyl methyl ether promotes the palladium-catalysed direct arylations in high yields with some heteroaromatic derivatives.¹¹ This solvent presents several advantageous features such as limited miscibility in water and low formation of peroxides. Moreover CPME can be manufactured by the addition of MeOH to cyclopentene. This process produces no apparent waste.¹² The good performance of KOAc as the base for this coupling is consistent with a concerted metallation deprotonation (CMD) pathway.¹³

Scheme 3

Using the best conditions, the scope of this reaction was examined using para-, meta- or ortho-substituted aryl bromides and also heteroaryl bromides (Scheme 4, Table 1). Other electron-deficient para-substituted aryl bromides also gave the desired 5-arylated DTE products 3b–3e (Table 1, entries 2–5). A good yield of 61% for 3d was obtained for the coupling of 2 with 4-bromoacetophenone; whereas reaction with methyl 4-bromobenzoate gave 3e in only 26% yield. Moderate yields of 3b and 3c were obtained in the presence of 4-bromonitrobenzene and 4-bromobenzaldehyde. As expected, the meta-substituted aryl bromide, 3-bromonitrobenzene, gave 3f in a similar yield to 4-bromonitrobenzene (Table 1, entry 6). A very low yield of 21% for 3g was obtained in the presence of 2-bromonaphthalene (Table 1, entry 7). This is probably due to a slow oxidative addition of this aryl bromide to palladium under these conditions. On the other hand, congested substrate, 2-bromobenzonitrile, was found to be very reactive, and gave 3h in 84% yield (Table 1, entry 8).

Scheme 4

Table 1 Direct arylation of 2 with (hetero)aryl bromides

Entry	Aryl bromide	Product	Yield (%)
Conditions: Pd(OAc)2 (0.05 equiv.), dppb (0.05 equiv.), aryl bromide (2 equiv.), 1 (1 equiv.), KOAc (3 equiv.), CPME, 40 h, 130 °C.a Aryl bromide (1 equiv.), KOAc (2 equiv.).
1		3a	69^a
2		3b	39
3		3c	40
4		3d	61
5		3e	26
6		3f	32
7		3g	21
8		3h	84
9		3i	55
10		3j	51^a
11		3k	80
12		3l	94
13		3m	63^a

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DTE derivatives have been also used as ligands for incorporation into transition metal complexes.^7e Therefore, preparative methods for the introduction of N-containing heterocycles such as pyridines,¹⁴ quinolines or pyrimidines remain a crucial issue for the elaboration of photoresponsive materials. We observed that the coupling of 3- or 4-bromopyridines with 2 also proceeds nicely to give 3i and 3j in 55% and 51% yields, respectively (Table 1, entries 9 and 10). Very high yields were obtained for the coupling of 2 with 3-bromoquinoline or 4-bromoisoquinoline to produce 3k and 3l in 80% and 94% yields, respectively (Table 1, entries 11 and 12). Finally, the reactivity of 5-bromopyrimidine was examined, and the desired product 3m was obtained in 63% yield (Table 1, entry 13).

A lower yield was obtained in the course of the coupling of 1 equiv. of 2 with 1 equiv. of 4,4′-dibromobiphenyl (Scheme 5). The desired product 3n was only obtained in 29% yield. However, this functionalised highly conjugated structure allows access to multi-DTE systems.¹⁵

Scheme 5

We also performed direct arylation reactions on 1 using two aryl bromides (Scheme 6). From 2 equiv. of 4-bromoisoquinoline and 1 equiv. of 1, the monoarylated product 4a was obtained in 41% yield; whereas the diarylated product could not be isolated. On the other hand, in the presence of 4 equiv. of 3-bromonitrobenzene, a mixture of the monoarylated product 4b and the diarylated product 4c was obtained in a 41 : 24 ratio.

Scheme 6

Conclusion

In summary, we have demonstrated that when appropriate reaction conditions are employed, the palladium-catalysed direct arylation of DTE derivatives proceeds with a variety of aryl bromides. It should be noted that this protocol, which employs a moderate loading of an air stable catalyst and a cheap base, is applicable to a wide range of functions, including reactive ones, such as formyl, acetyl, ester, nitrile or nitro on the aryl bromide. This procedure allowed us to synthesize new families of arylated DTE derivatives, including donor–acceptor (D–A) systems (3a). Such functional group tolerance allows the easy modification of the electronic structure of DTE derivatives, a strategy enabling the tuning of their photochromic properties. For all these reactions, CPME 99+% was used without any purification. As this solvent is hydrophobic, there is no need to dry it before use. The major by-products of these couplings are KBr/AcOH instead of metallic salts with more classical coupling procedures. For these reasons, this process should give a more economically viable and environmentally attractive access to several arylated dithienylperfluorocyclopentenes. In addition, coordination of DTE ligands will open up new perspectives for the design of photoswitchable molecules and materials.

Experimental Section

General

All reactions were performed in Schlenck tubes under argon. CPME of analytical grade was not distilled before use. Potassium acetate 99+ was used. Commercial aryl bromides were used without purification. ¹H (500 MHz), ¹³C (125 MHz) spectra were recorded in CDCl₃ solutions. Chemical shifts are reported in ppm relative to CDCl₃ (¹H: 7.29 and ¹³C: 77.0). Flash chromatography was performed on silica gel (230–400 mesh) using pentane/ether. 2 was prepared according to the reported procedure.^7b

General procedure

As a typical experiment, the reaction of the aryl bromide (1 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.147 g, 1.5 mmol) at 130 °C during 40 h in CPME (4 mL) in the presence of Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) under argon affords the corresponding coupling products 3a–n after evaporation of CPME and filtration on silica gel (pentane/ether) or (pentane/dichloromethane).

4-(4-{3,3,4,4,5,5-Hexafluoro-2-[5-(4-methoxyphenyl)-2-methylthiophen-3-yl]-cyclopent-1-enyl}-5-methylthiophen-2-yl)-benzonitrile (3a)¹⁶

The reaction of 4-bromobenzonitrile (0.091 g, 0.5 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.098 g, 1 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords the corresponding product 3a in 69% (0.197 g) isolated yield as a dark blue solid. ¹H NMR (500 MHz, CDCl₃): δ 7.69 (d, J = 8.6 Hz, 2H), 7.65 (d, J = 8.6 Hz, 2H), 7.49 (d, J = 8.8 Hz, 2H), 7.41 (s, 1H), 7.17 (s, 1H), 6.94 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 2.03 (s, 3H), 1.98 (s, 3H).

4-(4-{3,3,4,4,5,5-Hexafluoro-2-[5-(4-methoxyphenyl)-2-methylthiophen-3-yl]-cyclopent-1-enyl}-5-methylthiophen-2-yl)-nitrobenzene (3b)

The reaction of 4-bromonitrobenzene (0.202 g, 1 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.147 g, 1.5 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords product 3b in 39% (0.116 g) isolated yield as a dark green solid (mp: 184 °C). ¹H NMR (500 MHz, CDCl₃): δ 8.27 (d, J = 8.9 Hz, 2H), 7.70 (d, J = 8.9 Hz, 2H), 7.49 (d, J = 8.8 Hz, 2H), 7.46 (s, 1H), 7.17 (s, 1H), 6.94 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 2.05 (s, 3H), 1.99 (s, 3H). ¹³C NMR (125 MHz, CDCl₃): δ 159.6, 146.9, 144.1, 142.5, 140.2, 139.4, 139.3, 126.9, 126.7, 126.0, 125.8, 125.5, 125.2, 124.5, 121.1, 114.4, 55.4, 14.7, 14.5. Elemental analysis calcd (%) for C₂₈H₁₉F₆NO₃S₂ (595.58): C, 56.47; H, 3.22; found: C, 56.66; H, 3.32%.

4-(4-{3,3,4,4,5,5-Hexafluoro-2-[5-(4-methoxyphenyl)-2-methylthiophen-3-yl]-cyclopent-1-enyl}-5-methylthiophen-2-yl)-benzaldehyde (3c)¹⁷

The reaction of 4-bromobenzaldehyde (0.185 g, 1 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.147 g, 1.5 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords product 3c in 40% (0.115 g) isolated yield as a light blue solid. ¹H NMR (500 MHz, CDCl₃): δ 10.03 (s, 1H), 7.92 (d, J = 8.3 Hz, 2H), 7.72 (d, J = 8.3 Hz, 2H), 7.49 (d, J = 8.8 Hz, 2H), 7.46 (s, 1H), 7.18 (s, 1H), 6.94 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 2.04 (s, 3H), 1.99 (s, 3H).

1-[4-(4-{3,3,4,4,5,5-Hexafluoro-2-[5-(4-methoxyphenyl)-2-methylthiophen-3-yl]-cyclopent-1-enyl}-5-methylthiophen-2-yl)-phenyl]-ethanone (3d)

The reaction of 4-bromoacetophenone (0.199 g, 1 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.147 g, 1.5 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords product 3d in 61% (0.181 g) isolated yield as a dark blue solid (mp: 161 °C). ¹H NMR (500 MHz, CDCl₃): δ 7.99 (d, J = 8.5 Hz, 2H), 7.65 (d, J = 8.5 Hz, 2H), 7.49 (d, J = 8.8 Hz, 2H), 7.42 (s, 1H), 7.18 (s, 1H), 6.94 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 2.64 (s, 3H), 2.03 (s, 3H), 1.99 (s, 3H). ¹³C NMR (125 MHz, CDCl₃): δ 197.2, 159.6, 143.0, 142.4, 140.7, 140.3, 137.6, 136.1, 129.2, 127.0, 126.4, 126.1, 125.6, 125.4, 124.1, 121.2, 114.4, 55.4, 26.6, 14.7, 14.5. Elemental analysis calcd (%) for C₃₀H₂₂F₆O₂S₂ (592.61): C, 60.80; H, 3.74; found: C, 60.92; H, 3.91%.

Methyl 4-(4-{3,3,4,4,5,5-hexafluoro-2-[5-(4-methoxyphenyl)-2-methylthiophen-3-yl]-cyclopent-1-enyl}-5-methylthiophen-2-yl)-benzoate (3e)

The reaction of methyl 4-bromobenzoate (0.215 g, 1 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.147 g, 1.5 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords product 3e in 26% (0.079 g) isolated yield as a blue solid (mp: 170 °C). ¹H NMR (500 MHz, CDCl₃): δ 8.07 (d, J = 8.5 Hz, 2H), 7.62 (d, J = 8.5 Hz, 2H), 7.48 (d, J = 8.8 Hz, 2H), 7.41 (s, 1H), 7.17 (s, 1H), 6.94 (d, J = 8.8 Hz, 2H), 3.96 (s, 3H), 3.86 (s, 3H), 2.02 (s, 3H), 1.98 (s, 3H). ¹³C NMR (125 MHz, CDCl₃): δ 166.5, 159.6, 142.8, 142.3, 140.8, 140.3, 137.5, 130.4, 129.2, 127.0, 126.3, 126.1, 125.3, 123.4, 121.2, 114.4, 55.4, 55.2, 14.7, 14.5. Elemental analysis calcd (%) for C₃₀H₂₂F₆O₃S₂ (608.62): C, 59.20; H, 3.64; found: C, 59.43; H, 3.78%.

3-(4-{3,3,4,4,5,5-Hexafluoro-2-[5-(4-methoxyphenyl)-2-methylthiophen-3-yl]-cyclopent-1-enyl}-5-methylthiophen-2-yl)-nitrobenzene (3f)

The reaction of 3-bromonitrobenzene (0.202 g, 1 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.147 g, 1.5 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords product 3f in 32% (0.096 g) isolated yield as a light green oil. ¹H NMR (500 MHz, CDCl₃): δ 8.40 (s, 1H), 8.17 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H), 7.49 (d, J = 8.8 Hz, 2H), 7.42 (s, 1H), 7.18 (s, 1H), 6.94 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 2.04 (s, 3H), 1.99 (s, 3H). ¹³C NMR (125 MHz, CDCl₃): δ 159.6, 148.8, 143.0, 142.5, 140.2, 139.3, 135.0, 131.2, 130.0, 127.0, 126.4, 126.1, 125.5, 124.3, 122.3, 121.1, 120.3, 114.4, 55.4, 14.6, 14.5. Elemental analysis calcd (%) for C₂₈H₁₉F₆NO₃S₂ (595.58): C, 56.47; H, 3.22; found: C, 56.54; H, 3.35%.

4-(4-{3,3,4,4,5,5-Hexafluoro-2-[5-(naphth-2-yl)-2-methylthiophen-3-yl]-cyclopent-1-enyl-}5-methylthiophen-2-yl)-methoxyphenyl (3g)

The reaction of 2-bromonaphthalene (0.207 g, 1 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.147 g, 1.5 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords product 3g in 21% (0.063 g) isolated yield as a light green oil. ¹H NMR (500 MHz, CDCl₃): δ 7.99 (s, 1H), 7.90–7.83 (m, 3H), 7.70 (d, J = 8.5 Hz, 1H), 7.55–7.47 (m, 4H), 7.44 (s, 1H), 7.20 (s, 1H), 6.94 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 2.03 (s, 3H), 2.01 (s, 3H). ¹³C NMR (125 MHz, CDCl₃): 159.5, 142.3, 142.2, 133.5, 132.9, 130.7, 128.7, 128.0, 127.8, 127.0, 126.9, 126.8, 126.5, 126.3, 126.2, 126.1, 125.8, 124.1, 123.8, 122.8, 121.3, 114.4, 55.4, 14.6, 14.5. Elemental analysis calcd (%) for C₃₂H₂₂F₆OS₂ (600.64): C, 63.99; H, 3.69; found: C, 63.86; H, 3.81%.

2-(4-{3,3,4,4,5,5-Hexafluoro-2-[5-(4-methoxyphenyl)-2-methylthiophen-3-yl]-cyclopent-1-enyl}-5-methyl-thiophen-2-yl)-benzonitrile (3h)

The reaction of 2-bromobenzonitrile (0.182 g, 1 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.147 g, 1.5 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords product 3h in 84% (0.241 g) isolated yield as a blue oil. ¹H NMR (500 MHz, CDCl₃): δ 7.77 (d, J = 7.8 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 7.59 (d, J = 7.8 Hz, 1H), 7.57 (s, 1H), 7.50 (d, J = 8.8 Hz, 2H), 7.45 (t, J = 7.8 Hz, 1H), 7.19 (s, 1H), 6.94 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 2.04 (s, 3H), 2.03 (s, 3H). ¹³C NMR (125 MHz, CDCl₃): δ 159.5, 143.6, 142.3, 140.6, 137.2, 136.6, 134.2, 133.0, 129.5, 128.1, 127.4, 126.9, 126.1, 126.0, 125.4, 121.1, 118.3, 114.4, 110.4, 55.4, 14.6, 14.4. Elemental analysis calcd (%) for C₂₉H₁₉F₆NOS₂ (575.59): C, 60.51; H, 3.33; found: C, 60.72; H, 3.50%.

3-(4-{3,3,4,4,5,5-Hexafluoro-2-[5-(4-methoxyphenyl)-2-methylthiophen-3-yl]-cyclopent-1-enyl}-5-methylthiophen-2-yl)-pyridine (3i)

The reaction of 3-bromopyridine (0.158 g, 1 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.147 g, 1.5 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords product 3i in 45% (0.124 g) isolated yield as a blue solid (mp: 146 °C). ¹H NMR (500 MHz, CDCl₃): δ 8.83 (s, 1H), 8.56 (d, J = 4.8 Hz, 1H), 7.84 (d, J = 7.9 Hz, 1H), 7.49 (d, J = 8.8 Hz, 2H), 7.37–7.32 (m, 2H), 7.17 (s, 1H), 6.94 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 2.04 (s, 3H), 1.99 (s, 3H). ¹³C NMR (125 MHz, CDCl₃): δ 159.5, 151.5, 148.9, 146.7, 142.4, 140.3, 138.3, 135.8, 132.7, 129.5, 127.0, 126.3, 126.1, 125.5, 123.7, 121.2, 114.4, 55.4, 14.6, 14.5. Elemental analysis calcd (%) for C₂₇H₁₉F₆NOS₂ (551.57): C, 58.79; H, 3.47; found: C, 59.16; H, 3.42%.

4-(4-{3,3,4,4,5,5-Hexafluoro-2-[5-(4-methoxyphenyl)-2-methylthiophen-3-yl]-cyclopent-1-enyl}-5-methylthiophen-2-yl)-pyridine (3j)¹⁸

The reaction of 4-bromopyridine hydrochloride (0.100 g, 0.5 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.098 g, 1 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords product 3j in 51% (0.140 g) isolated yield as a green solid. ¹H NMR (500 MHz, CDCl₃): δ 8.62 (d, J = 5.9 Hz, 2H), 7.50 (s, 1H), 7.48 (d, J = 8.7 Hz, 2H), 7.43 (d, J = 5.9 Hz, 2H), 7.17 (s, 1H), 6.94 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H), 2.04 (s, 3H), 1.97 (s, 3H).

3-(4-{3,3,4,4,5,5-Hexafluoro-2-[5-(4-methoxyphenyl)-2-methylthiophen-3-yl]-cyclopent-1-enyl}-5-methylthiophen-2-yl)-quinoline (3k)

The reaction of 3-bromoquinoline (0.208 g, 1 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.147 g, 1.5 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords product 3k in 80% (0.240 g) isolated yield as a dark green solid (mp: 139 °C). ¹H NMR (500 MHz, CDCl₃): δ 9.14 (s, 1H), 8.24 (s, 1H), 8.13 (d, J = 8.0 Hz, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.74 (t, J = 8.0 Hz, 1H), 7.60 (t, J = 8.0 Hz, 1H), 7.50 (d, J = 8.8 Hz, 2H), 7.48 (s, 1H), 7.20 (s, 1H), 6.94 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 2.07 (s, 3H), 2.02 (s, 3H). ¹³C NMR (125 MHz, CDCl₃): δ 159.6, 148.0, 147.4, 142.6, 142.4, 140.3, 138.6, 131.2, 129.6, 129.4, 127.8, 127.7, 127.4, 126.9, 126.5, 126.4, 126.1, 125.6, 123.9, 121.2, 114.4, 55.4, 14.6, 14.5. Elemental analysis calcd (%) for C₃₁H₂₁F₆NOS₂ (601.63): C, 61.89; H, 3.52; found: C, 61.76; H, 3.49%.

4-(4-{3,3,4,4,5,5-Hexafluoro-2-[5-(4-methoxyphenyl)-2-methylthiophen-3-yl]-cyclopent-1-enyl}-5-methylthiophen-2-yl)-isoquinoline (3l)

The reaction of 4-bromoisoquinoline (0.208 g, 1 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.147 g, 1.5 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords product 3l in 94% (0.283 g) isolated yield as a dark blue solid (mp: 134 °C). ¹H NMR (500 MHz, CDCl₃): δ 9.26 (s, 1H), 8.59 (s, 1H), 8.10 (d, J = 8.0 Hz, 1H), 8.05 (d, J = 8.0 Hz, 1H), 7.73 (t, J = 8.0 Hz, 1H), 7.67 (t, J = 8.0 Hz, 1H), 7.51 (d, J = 8.8 Hz, 2H), 7.26 (s, 1H), 7.21 (s, 1H), 6.95 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 2.17 (s, 3H), 2.10 (s, 3H). ¹³C NMR (125 MHz, CDCl₃): δ 159.5, 152.8, 143.4, 142.9, 142.3, 140.2, 135.9, 133.9, 131.2, 128.4, 128.1, 128.0, 127.6, 126.9, 126.1, 125.7, 125.6, 125.2, 124.0, 121.3, 114.4, 55.4, 14.5, 14.4. Elemental analysis calcd (%) for C₃₁H₂₁F₆NOS₂ (601.62): C, 61.89; H, 3.52; found: C, 61.77; H, 3.41%.

5-(4-{3,3,4,4,5,5-Hexafluoro-2-[5-(43-methoxyphenyl)-2-methylthiophen-3-yl]-cyclopent-1-enyl}-5-methylthiophen-2-yl)-pyrimidine (3m)

The reaction of 5-bromopyrimidine (0.080 g, 0.5 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.098 g, 1 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 20 h affords product 3m in 63% (0.174 g) isolated yield as a yellow solid (mp: 146 °C). ¹H NMR (500 MHz, CDCl₃): δ 9.16 (s, 1H), 8.92 (s, 2H), 7.49 (d, J = 8.7 Hz, 2H), 7.41 (s, 1H), 7.16 (s, 1H), 6.95 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H), 2.07 (s, 3H), 1.99 (s, 3H). ¹³C NMR (125 MHz, CDCl₃): δ 159.6, 157.6, 153.2, 143.8, 142.6, 140.2, 134.2, 127.7, 126.9, 126.7, 126.0, 125.4, 124.9, 121.1, 114.4, 55.4, 14.7, 14.5. Elemental analysis calcd (%) for C₂₆H₁₈F₆N₂OS₂ (552.56): C, 56.52; H, 3.28; found: C, 56.75; H, 3.19%.

4-(4-{3,3,4,4,5,5-Hexafluoro-2-[5-(4-bromobiphenyl)-2-methylthiophen-3-yl]-cyclopent-1-enyl}-5-methylthiophen-2-yl)-methoxyphenyl (3n)¹⁵

The reaction of 4,4′-dibromobiphenyl (0.156 g, 0.5 mmol), 2 (0.237 g, 0.5 mmol) and KOAc (0.098 g, 1 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords product 3n in 29% (0.051 g) isolated yield as a dark blue solid. ¹H NMR (500 MHz, CDCl₃): δ 7.63 (d, J = 8.8 Hz, 2H), 7.61 (d, J = 8.5 Hz, 2H), 7.59 (d, J = 8.5 Hz, 2H), 7.50 (d, J = 8.5 Hz, 2H), 7.48 (d, J = 8.5 Hz, 2H), 7.35 (s, 1H), 7.19 (s, 1H), 6.94 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 2.02 (s, 3H), 1.99 (s, 3H).

4-{4-[3,3,4,4,5,5-Hexafluoro-2-(2-methylthiophen-3-yl)-cyclopent-1-enyl]-5-methylthiophen-2-yl}-isoquinoline (4a)

The reaction of 4-bromoisoquinoline (0.208 g, 1 mmol), 1 (0.184 g, 0.5 mmol) and KOAc (0.147 g, 1.5 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords product 4a in 41% (0.101 g) isolated yield as a pink solid (mp: 113 °C). ¹H NMR (500 MHz, CDCl₃): δ 9.26 (s, 1H), 8.57 (s, 1H), 8.12–8.04 (m, 2H), 7.78 (t, J = 6.9 Hz, 1H), 7.70 (t, J = 6.9 Hz, 1H), 7.25 (d, J = 5.3 Hz, 1H), 7.22 (s, 1H), 7.14 (d, J = 5.3 Hz, 1H), 2.09 (s, 3H), 2.07 (s, 3H). ¹³C NMR (125 MHz, CDCl₃): δ 152.8, 143.5, 142.9, 141.7, 135.8, 133.9, 131.2, 128.4, 128.1, 128.0, 127.6, 127.2, 125.7, 125.2, 125.0, 124.0, 123.8, 14.3, 14.2. Elemental analysis calcd (%) for C₂₄H₁₅F₆NS₂ (495.51): C, 58.17; H, 3.05; found: C, 58.29; H, 3.18%.

4-{4-[3,3,4,4,5,5-Hexafluoro-2-(2-methylthiophen-3-yl)-cyclopent-1-enyl]-5-methylthiophen-2-yl}-nitrobenzene (4b) and 4-(4-{3,3,4,4,5,5-hexafluoro-2-[5-(4-nitrophenyl)-2-methylthiophen-3-yl]-cyclopent-1-enyl}-5-methylthiophen-2-yl)-nitrobenzene (4c)

The reaction of 4-bromonitrobenzene (0.404 g, 2 mmol), 1 (0.184 g, 0.5 mmol) and KOAc (0.294 g, 1.5 mmol) with Pd(OAc)₂ (0.005 g, 0.025 mmol) and dppb (0.010 g, 0.025 mmol) in CPME (4 mL) at 130 °C during 40 h affords a mixture of product 4b in 41% (0.100 g) isolated yield as a blue solid (mp: 172 °C), and of product 4c in 24% (0.73 g) isolated yield as a dark blue solid (mp: 214 °C).

4b ¹H NMR (500 MHz, CDCl₃): δ 8.27 (d, J = 8.9 Hz, 2H), 7.69 (d, J = 8.9 Hz, 2H), 7.44 (s, 1H), 7.22 (d, J = 5.3 Hz, 1H), 7.10 (d, J = 5.3 Hz, 1H), 2.01 (s, 3H), 1.97 (s, 3H). ¹³C NMR (125 MHz, CDCl₃): δ 146.9, 144.1, 141.8, 139.4, 139.3, 127.1, 126.6, 125.8, 125.2, 124.8, 124.5, 124.0, 14.5, 14.4. Elemental analysis calcd (%) for C₂₁H₁₃F₆NO₂S₂ (489.46): C, 51.53; H, 2.68; found: C, 51.61; H, 2.87%.

4c ¹H NMR (500 MHz, CDCl₃): δ 8.28 (d, J = 8.9 Hz, 4H), 7.71 (d, J = 8.9 Hz, 4H), 7.47 (s, 2H), 2.06 (s, 6H). ¹³C NMR (125 MHz, CDCl₃): δ 147.0, 144.0, 139.8, 139.2, 128.4, 125.9, 124.6, 124.4, 14.8. Elemental analysis calcd (%) for C₂₇H₁₆F₆N₂O₄S₂ (610.55): C, 53.11; H, 2.64; found: C, 53.23; H, 2.74%.

Acknowledgements

K. B. is grateful to CNRS and “Conseil regional de Bretagne” for a grant. We thank the CNRS and “Rennes Metropole” for providing financial support.

Notes and references

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Footnotes

† Dedicated to Dr Hubert Le Bozec on the occasion of his 60th birthday.

‡ Electronic supplementary information (ESI) available. See DOI: 10.1039/c2cy00491g

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