Synthesis of Sulfur-Bridged Polycycles via Pd-Catalyzed

Letter pubs.acs.org/OrgLett

Synthesis of Sulfur-Bridged Polycycles via Pd-Catalyzed Dehydrogenative Cyclization Binjie Wang,† Yue Liu,† Cong Lin,† Yiming Xu,† Zhanxiang Liu,† and Yuhong Zhang*,†,‡ †

ZJU-NHU United R&D Center, Department of Chemistry, Zhejiang University, Hangzhou 310027, China State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China

‡

S Supporting Information *

ABSTRACT: A general approach to sulfur-bridged polycycles by palladium-catalyzed double C(sp2)−H bond oxidative cyclization is presented. This protocol afforded diverse sulfur-bridged five-, six-, and seven-membered polycycles in moderate to good yields with a tolerance for a wide variety of functional groups. A sulfide-bridged six-membered pyrene−thienoacene compound was synthesized readily using this method, and excellent performance for photoluminescence quantum yield was observed.

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sulfur-bridged six- or seven-membered heterocycles still stands as a challenge in organic synthesis. It is noteworthy that sulfur-based six-membered heterocycles are known to possess interesting optoelectronic properties and show more remarkable properties than aromatic thiophenes.3e A recent study revealed that the oxidation state of the bridging sulfur atom (sulfide, sulfoxide, and sulfone) had a decisive effect on the quantum efficiency of the materials.3d However, the application of sulfur-based six-membered heterocycles is significantly restricted due to the lack of reliable preparation protocols. Considering the very limited methodologies for sulfur-based six- and seven-membered heterocycles,4g−i the development of new efficient protocols for these heterocycles is highly desirable. Our group has a long-standing interest in the C−H functionalization directed by sulfur-containing functional groups.8 We have developed the palladium-catalyzed olefination,8a,b arylation,8c and acetoxylation of arenes using sulfide or sulfoxide as the directing groups. Herein, we report a novel method for the synthesis of sulfoxide-bridged five-, six-, and seven-membered fused polycycles by Pd-catalyzed intramolecular C(sp2)−H/C(sp2)−H oxidative coupling. The transformation is supposed to be occurring through a sulfoxide-assisted palladium-catalyzed C−H bond cleavage process. The sulfoxide-bridged polycycles are able to be further transferred into the corresponding sulfide- or sulfone-bridged polycycles by easy reduction or oxidation. A sulfide-bridged sixmembered pyrene−thienoacene compound is readily prepared using our method, and the preliminary study revealed its excellent fluorescence performance to give a photoluminescence quantum yield as high as 0.48. Initially, we chose to study the dehydrogenative cyclization by the use of sulfoxide 1aa as the model substrate, which is easily prepared from benzenethiol and benzyl bromide.

here has been great interest in sulfur-containing heterocycles because of their potential biological activity,1 pharmaceutical significance,2 and wide application in functional materials.3 Driven by the growing demand of these structures (Figure 1), great efforts have been devoted toward the

Figure 1. Selected useful sulfur-bridged polycycles.

continual development of new and improved protocols.4 In recent years, transition-metal-catalyzed oxidative cross-coupling of two C(sp2)−H bonds has emerged as a powerful tool for the synthesis of heterocycles.5 A wide variety of functionalized xanthones,6a,e,f carbazoles,6b,c and furan derivatives6d have been synthesized through the double C−H bond dehydrogenative cyclization in order to both improve the efficiency and extend the substrate scope. Despite the remarkable advances of C−H/ C−H coupling, engagement of sulfur-based heterocycle synthesis by using this strategy has proven to be difficult.7 A recent breakthrough was achieved by the Antonchick group, who employed sulfoxide as a new traceless directing group that induced the formation of dibenzothiophenes by palladium catalysis.4c Under their reaction conditions, the initially formed six-membered cyclic sulfoxide possibly underwent the Pummerer rearrangement to finally give the dibenzothiophene derivatives. Very recently, Zhou et al. reported a beautiful example of the synthesis of dibenzothiophenes from diaryl sulfides through Pd-catalyzed C(sp2)−H/ C(sp2)−H oxidative cyclization.4f Currently, the majority of success was obtained for the synthesis of sulfide-bridged fivemembered heterocycles. A method for the preparation of © XXXX American Chemical Society

Received: July 19, 2014

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products (Scheme 1, 2q−2s). The produced sulfur-based polycycles might be used as organic semiconducting materials.3e Dibenzothiophene-S-oxides are interesting triplet oxygen precursors and were recently prepared by palladium catalysis from 2-bromo-diarylsulfinyl moieties.1a To our delight, the present method of direct C(sp2)−H/C(sp2)−H coupling could be utilized for the synthesis of dibenzothiophene-S-oxides (fivemembered sulfur-bridged polycycles) (Scheme 2, 4a−4c),

Encouragingly, in the presence of 10 mol % of PdCl2 and AgOAc in 1,1,2,2-tetrachloroethane (TTCE) at 100 °C for 48 h, the sulfoxide-bridged six-membered polycycle 2aa was isolated in 41% yield. Under this modified condition of Antonchik’s work (see Supporting Information), a wide array of sulfoxides were subjected to the reaction to give the corresponding products as shown in Scheme 1. It was observed Scheme 1. Synthesis of Six-Membered Sulfur-Bridged Polycyclesa

Scheme 2. Synthesis of Five- and Seven-Membered SulfurBridged Polycyclesa

a

Reaction conditions: sulfoxide derivative (0.2 mmol), PdCl2 (0.02 mmol), AgOAc (0.8 mmol), iodobenzene (0.4 mmol), AcOH (0.8 mmol) in 2 mL TTCE at 100 °C for 48 h, in a sealed tube. b 120 °C, 24 h. c 110 °C. d isolated as isomers (1:1.8). e Isolated as isomers (1:1.5).

that substrates with both electron-withdrawing and -donating groups in a sulfoxide aryl ring participated in the reaction to give the cyclization product in moderate to good yields. Better yields were achieved when the electron density of the aryl ring was improved through the electron-donating substituent (Scheme 1, 2aa−2af). However, the ortho-substituted derivatives failed to afford the desired product, possibly owing to the steric interactions between the sulfoxide group and the ortho substituent (Scheme 1, 2ag). The substrate generality of the benzyl ring was next examined (Scheme 1, 2b−2s). We were pleased to find that a variety of substituents, including −CH3, −OMe, −tert-butyl, −OCF3, −F, −Cl, and −Br, were tolerated to give the desired six-membered sulfur-bridged polycycles. Generally, the electron-rich substrates presented higher activity than that of the electronic-deficient arenes. It should be noted that the selective C(sp2)−H/C(sp2)−H cross-coupling is possible in the presence of halogen functionality (Scheme 1, 2j−2p), providing a useful handle for further cross-coupling reactions. Notably, when 1-(p-tolylsulfinyl)naphthalene was used as the substrate, the exclusive α-carbon−hydrogen bond coupling product was generated (Scheme 1, 2q). In contrast, the β-C−H coupling product was not observed, showing excellent regioselectivity. Other acene groups such as phenanthryl and pyrenyl also presented high regioselectivity to give the α-C−H coupling

a Reaction conditions: sulfoxide derivative (0.2 mmol), PdCl2 (0.02 mmol), AgOAc (0.8 mmol), iodobenzene (0.4 mmol), AcOH (0.8 mmol) in 2 mL of TTCE at 100 °C for 48 h, in a sealed tube. b 120 °C. c 60 h.

which could be readily transferred to the useful dibenzothiophenes after reduction.8f Very importantly, the sevenmembered sulfur-bridged polycycle, which is difficult to be constructed from simple starting materials, could be formed under our reaction conditions with longer tether substrates (Scheme 2, 4d−4n). For example, the reaction of o-, m-, and pmethyl arenes resulted in the seven cycles in 45−67% yields (Scheme 2, 4e−4g). Halogen-containing substrates tolerated the reaction conditions to give the desired products, but a longer reaction time was required (4i−4m). 2-Naphthalenyl sulfoxide underwent the reaction smoothly to afford a 51% yield. To investigate the reaction mechanism, an intermolecular isotope kinetic experiment was performed. Benzyl(p-tolyl)sulfoxide 1aa and its deuterated analogue 1aa-d5 were equivalently subjected to the reaction (Scheme 3). A kinetic isotope effect (KIE) value of 3.54 was observed, implicating that the C(sp2)−H cleavage of the benzyl group might be the rate-determining step in the catalytic cycle. B

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Scheme 3. Isotope Kinetic Experiment

Scheme 5. Plausible Mechanism

To gain insight into the reaction mechanism, control experiments were performed using the palladacycle complex A (Scheme 4).8b It was found that the cyclization is not able to Scheme 4. Mechanism Investigation

Pummerer rearrangement to afford dibenzothiophene 5 under Antochik’s condition.4c Pyrene is a well-known chromophore and has been used as an emitting material for organic electronic devices due to its high absorption coefficients and fluorescence quantum yield. The utility of our methodology is illustrated by a rapid synthesis of pyrene-thienoacene compound 6 as shown in Scheme 6. The cyclization of sulfoxide 1s affords bathochromic

occur by simply heating the solution of palladacycle complex A, showing the formation of intermediate D requires internal help (Scheme 4, eq 1). No reaction was observed when 2 equiv of iodobenzene were added in the solution of complex A (Scheme 4, eq 2), illustrating that acceleration of the reaction rate through the formation of Pd(IV) by the oxidative addition of the palladacycle complex A to iodobenzene is unlikely. In contrast, when acetic acid or silver acetate was added, the cyclized product was formed and the high yield could be obtained by controlling the amount of acetic acid (Scheme 4, eqs 3 and 4). It is interesting that the best reaction efficiency was observed in the presence of both iodobenzene and acetic acid (Scheme 4, eq 5). Based on our previous studies, a plausible reaction mechanism is proposed for this new C(sp2)−H/C(sp2)−H coupling reaction as shown in Scheme 5. Directed by sulfoxide as a chelation group, the ortho C(sp2)−H bond of the benzyl group is activated to give the five-membered cyclopalladated intermediate A, which experiences difficulty in undergoing the subsequent intramolecular C(sp2)−H palladation in the presence of iodobenzene or by simply heating. An electrophilic palladation pathway is possible for this sulfoxide assisted palladation because the lower reactivity of the substrates with an electron-deficient aromatic ring partially is observed (Scheme 1, entries 2j−2p). Acetic acid or silver acetate may transfer the intermediate A to intermediate B, which is able to undergo the second palladation. Since no strong electronic bias of aromatic rings was observed for the second intramolecular palladation (Scheme 1, entries 2aa−2af), a concerted palladium−carbon/carbon−hydrogen bond formation/cleavage pathway is reasonable.9 The reductive elimination of the intermediate D liberates the sulfur-bridged polycycle 2aa with the formation of Pd(0), which is oxidized by a silver salt to regenerate the Pd(II) for the next catalytic cycle. It is also reasonable to assume that iodobenzene promotes the formation of intermediate D through a Pd(IV) intermediate after the formation of intermediate B.4c The product 2aa went through

Scheme 6. Synthesis of Pyrene Thienoacenes (PTAs)

shifts for absorption at 354 to 385 nm in CH2Cl2, leading to a drop in the photoluminescence quantum yield from 0.24 (compound 1s) to 0.17 (2s). Sulfide-bridged six-membered pyrene−thienoacene 6 shows a pronounced quantum yield of 0.48, which is much higher than that for most of its sulfidebridged five-membered thiophene analogues reported in literature,3e and also much better than that of parent pyrene.10 In contrast, sulfoxide-bridged six-membered pyrene−thienoacene 2s gives a relatively lower photoluminescence quantum yield. Compounds 1s, 6, and 2s exhibit good thermal and oxidative stability in air. In summary, we have developed an efficient sulfoxide-assisted C(sp2)−H/C(sp2)−H coupling reaction that leads to the straightforward synthesis of five-, six-, and seven-membered sulfur-bridged polycycles by palladium catalysis. The precursors for this ring-closing reaction are readily prepared by the C

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nucleophilic substituent reaction of arylthiol and alky bromide, which allows diverse motifs of sulfur-based polycycles to be easily designed. Further investigation for preparing materialrelevant compounds is currently underway.

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ASSOCIATED CONTENT

* Supporting Information S

Additional experimental data, characterization of new compounds, and spectra data. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Funding from NSFC (No. 21272205), NBRPC (No. 2011CB936003), and the Program for Zhejiang Leading Team of S&T Innovation (2011R50007) is acknowledged.

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REFERENCES

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