Letter Cite This: Org. Lett. 2018, 20, 5439−5443
pubs.acs.org/OrgLett
Cyclization of 2‑Biphenylthiols to Dibenzothiophenes under PdCl2/ DMSO Catalysis Tao Zhang, Guigang Deng, Hanjie Li, Bingxin Liu, Qitao Tan,* and Bin Xu* Department of Chemistry, Innovative Drug Research Center, Shanghai University, Shanghai, 200444, China
Org. Lett. 2018.20:5439-5443. Downloaded from pubs.acs.org by UNIV OF SOUTH DAKOTA on 09/08/18. For personal use only.
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ABSTRACT: A palladium-catalyzed synthesis of dibenzothiophenes from 2biphenylthiols is described. This highly efficient reaction employs a simple PdCl2/ DMSO catalytic system, in which PdCl2 is the sole metal catalyst and DMSO functions as an oxidant and solvent. This transformation has broad substrate scope and operational simplicity and proceeds in high yield. The synthetic utility was demonstrated by the facile synthesis of helical dinapthothiophene 3 and an eminent organic semiconductor DBTDT 4. Importantly, highly strained trithiasumanene 5, a buckybowl of considerable synthetic challenge, was observed under this catalytic system.
D
ibenzo-fused thiophenes are privileged scaffolds with numerous applications in pharmaceuticals and organic electronics.1 For example, compound BMS-251873 was reported to be a selective topoisomerase I active agent that showed curative antitumor activity against prostate carcinoma xenografts (Figure 1).2 11-Arylbenzo[b]naphtho[2,3-d]-
Several straightforward methods for the synthesis of dibenzothiophenes have been reported,1,9 which generally require multistep procedures from halogenated or metalated compounds. Recently, Jiang and Shimizu independently reported an elegant synthesis of dibenzothiophenes by the reaction of diaryliodonium salts with S8 or AcSK.10 Sakai et al. reported the preparation of dibenzothiophene derivatives using 2-biphenylyl disulfides in the presence of molecular iodine or a palladium catalyst.11 Over the past decade, several transitionmetal-catalyzed reactions have been developed for the synthesis of dibenzothiophenes through different C−H functionalization strategies (Figure 2a).12 Dibenzothiophenes constitute a family of 9-heterofluorenes that include carbazoles, dibenzofurans, dibenzosiloles, and dibenzophospholes. Transition-metal-catalyzed intramolecular cyclization of the corresponding “X−H” containing 2-biphenyl precursors via C−H functionalization and C−X bond formation is an ideal protocol to produce 9-heterofluorenes (Figure 2b). For example, Buchwald and Gaunt reported the synthesis of carbazoles from the corresponding 2-aminobiphenyl derivatives through palladium-catalyzed C−H functionalization/C−N bond formation.13 Liu and Yoshikai developed the palladium-catalyzed synthesis of dibenzofurans from 2-arylphenols.14 An elegant rhodium-catalyzed synthesis of silafluorene derivatives was reported by Takai from biphenylhydrosilanes via cleavage of the Si−H and C−H bonds.15,16 Dibenzophosphole oxides were also obtained from secondary hydrophosphine oxides with a biphenyl group by dehydrogenation in the presence of a catalytic amount of palladium(II) acetate.17 However, synthesis of dibenzothiophenes from 2-biphenylthiols through transition-metal-catalyzed intramolecular cyclization has scarcely been reported probably due to the known poisoning effect of phenylthiols on transition metals.18
Figure 1. Representative benzo-fused thiophenes as pharmaceuticals or organic functional materials.
thiophene was reported to be a selective PTPase inhibitor that functions as an oral antidiabetic agent.3 Notably, the use of ladder-type small molecule 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C8-BTBT) as an organic semiconductor has yielded thin-film transistors with average carrier mobilities as high as 16.4 cm2 V−1 s−1.4 Dibenzo[d,d′]thieno[3,2-b;4,5b′]dithiophene (DBTDT) is an eminent p-type semiconductor in organic plastics.5 Employing the disc-shaped dithioperylene in the organic field-effect transistors (OFETs) produced carrier mobilities as high as 2.13 cm2 V−1 s−1 and an on/off ratios up to 106 for single-crystalline nanoribbons by a solution process.6 Trithiasumanene, possessing a bowl-shaped geometry with three embedded benzo-fused thiophene rings,7 is useful for molecular recognition.8 © 2018 American Chemical Society
Received: July 25, 2018 Published: August 14, 2018 5439
DOI: 10.1021/acs.orglett.8b02347 Org. Lett. 2018, 20, 5439−5443
Letter
Organic Letters
semiconductor DBTDT 4, and the preparation of highly strained buckybowl trithiasumanene 5. The reaction conditions were optimized based on the model transformation of 4′-methyl-2-biphenylthiol 1a (Table 1). Initial attempts employing PdCl2 as the catalyst and copper acetate as the oxidant in acetic acid at 120 °C afforded the desired product 2a in 57% yield (entry 1). The use of n-butyric acid as the solvent led to higher yields (entries 2−3). When the reaction was carried out at 140 °C, an 80% yield was obtained. No apparent product was observed in the absence of an oxidant when the reaction was performed in the neat acid (entry 5). The reaction in DMSO afforded the product in a comparable yield to the acid (entry 6). Interestingly, an external oxidant was found to be unnecessary for the reaction carried out in DMSO, which gave an excellent yield (entry 7). Surprisingly, palladium acetate only gave a trace amount of the product (entry 8). Pd(PPh3)4 afforded the desired product, albeit in a much lower yield (entry 9). Copper acetate was not an effective catalyst for this transformation (entry 10). Other solvents did not give the product in the absence of an oxidant, which indicates that DMSO plays a role as an oxidant (entries 11−14). No product was obtained in the absence of a metal catalyst (entry 15). Lowering the temperature or performing the reaction under an air or oxygen atmosphere decreased the yields (entries 16−18). With the optimized conditions in hand, the substrate scope was next investigated. As shown in Scheme 1, various dibenzothiophenes were prepared in good to excellent yields. The 2-biphenylthiols with functional groups on the 4′ position, regardless of their electronic properties, gave the cyclized products in excellent yields (2a−2h). Interestingly, a C−Br bond remained intact under the conditions (2d). The methyl group on the 2′ position of the 2-biphenylthiol did not affect the cyclization (2i). Notably, substrate 1j with a methyl group
Figure 2. Synthesis of dibenzothiophenes.
We herein report an efficient synthesis of dibenzothiophenes via C−H functionalization and C−S bond formation from readily available 2-biphenylthiols under simple PdCl2/DMSO catalysis (Figure 2c). The notable features of the reaction are as follows: (1) no need for additives, such as ligands, external oxidants, or bases; (2) DMSO as the solvent and oxidant; (3) broad substrate scope; (4) multifold cyclization also possible. The utilities of this method have been demonstrated by a facile synthesis of helical dinapthothiophene 3, p-type organic Table 1. Optimization of the Conditionsa
entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17c 18d
catalyst
oxidant (equiv)
PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 Pd(OAc)2 Pd(PPh3)4 Cu(OAc)2 PdCl2 PdCl2 PdCl2 PdCl2 − PdCl2 PdCl2 PdCl2
Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 − Cu(OAc)2 − − − − − − − − − − − −
solvent
(1.5) (1.5) (2.0) (2.0)
AcOH n-PrCO2H n-PrCO2H n-PrCO2H n-PrCO2H DMSO DMSO DMSO DMSO DMSO toluene DMF NMP AcOH DMSO DMSO DMSO DMSO
(2.0)
temp [°C] 120 120 120 140 140 140 140 140 140 140 140 140 140 140 140 120 140 140
yieldb [%] 57 65 71 80
