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• N-Substituted carbazoles are privileged scaffolds in various natural products and functional materials [1]. For instance, carbazoles have many important biological activities, such as anti-cancer, anti-viral and anti-inflammatory [2]. And in the field of materials science, carbazole derivatives have been widely studied as organic light-emitting devices (OLEDs) and solar cells materials for their unique optical and electrochemical properties [3]. N-Arylated carbazoles, such as 4, 40-N, N'-dicarbazol-biphenyl (CBP), are a kind of small molecule OLED materials, which are generally prepared by C—N coupling reactions [4]. Ullmann condensation and Buchwald-Hartwig coupling reaction are general and effective strategies for construction of N-substituted carbazoles via forming C—N bonds [5]. However, due to the steric hindrance and low nucleophilicity of N-atom in the aromatic system, traditional methods often require a high reaction temperature, strong base and pre-activated starting materials. Hence, the development of alternative way to N-substituted carbazoles is highly demanded.

  Hypervalent iodine reagents, especially benziodoxole derivatives, have become a class of significant group-transfer reagents in organic synthesis [6]. In the past decades, several studies of the benziodoxolone-based hypervalent iodine reagents containing I— N bonds have been reported, that makes it possible to construct C—N bonds by using hypervalent iodine reagents (Scheme 1A). In 1994, Zhdankin and co-workers first reported a thermally stable azidobenziodoxolone compound, which was an efficient reagent for direct C—H azidation reactions [7]. Afterwards, in 1997, Zhdankin's group reported benziodoxolone derivatives containing amido moiety, and these compounds could be used for amidation of C—H bonds [8]. In 2015, Kiyokawa and co-workers developed a protocol for preparing the hypervalent iodine reagents including a phthalimidate group, which provided a new approach for oxidative amination reactions [9]. Recently, Bolm's group demonstrated a range of sulfoximidoyl-containing hypervalent iodine reagents, and these reagents could be utilized to add to styrenes by a photocatalytic process [10]. Moreover, in 2017, Waser's group reported a series of indole-and pyrrole-containing benziodoxolone reagents [11]. The PyrroleBX and IndoleBX were used for C–H functionalization of arenes to give C2 and C3 substituted pyrroles and indoles. In this context, we would like to develop a method to synthesize carbazole-containing benziodoxolone derivatives, aiming at expanding the synthetic methods of N-arylated carbazole derivatives. Herein, we reported a protocol to synthesize carbazole-containing hypervalent iodine(Ⅲ) reagents in good to excellent yields from N-TMS-carbazoles and acetoxybenziodoxolone. These new reagents are bench-stable and can be used for the Cu-catalyzed C—N coupling reaction of carbazole and aromatic heterocyclic substrates (Scheme 1B).

  Scheme 1

  

  Scheme 1.  Nitrogen-containing benziodoxolone derivatives.

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  We first focused on the synthesis of carbazole-containing hypervalent iodine reagents. We chose N-TMS-carbazoles as the carbazole source to react with acetoxybenziodoxolone for synthesizing the desired compounds. To our delight, with 10 mol% KF as an additive, acetoxybenziodoxolone and 1a were mixed in dry CH₃CN and stirred for 24 h at room temperature, the desired hypervalent iodine product 2a was obtained in 91% yield (Scheme 2). When non-dry CH₃CN was used as the solvent, the yield of product 2a decreased obviously, to only 32%. Furthermore, hypervalent iodine reagents containing 3, 6-dichloro-, dibromo-, and diiodine-substituted carbazole groups all went smoothly to afford the desired products in good yield. In addition, the synthesis of hypervalent iodine product 2a and 2c could be easily scaled up to the 10 mmol scale without yield decreased. All the carbazolecontaining hypervalent iodine reagents are stable under ambient condition, and soluble in DCM, CHCl₃ and DMSO, but almost insoluble in CH₃CN at room temperature. When N-TMS-carbazoles were replaced by carbazoles (N—H) or metal carbazolide (metal = Li, Na or K) to react with acetoxybenziodoxolone in a variety of reaction conditions, no desired products 2 were obtained.

  Scheme 2

  

  Scheme 2.  Scope of carbazole-containing hypervalent iodine reagents. Reaction conditions: KF (10 mol%), 1 (4.0 mmol), acetoxybenziodoxolone (4.0 mmol), in dry CH₃CN (10 mL) at room temperature. Isolated yields. ^a10 mmol scale.

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  The structure of 2a was further confirmed by XRD. As shown in Fig. 1, the N1-I1-O1 angle of 170.74(15)° and the N1-I1-C1 angle of 92.9(2)° show the molecule has a distorted T-shape, in accord with the typical structure of benziodoxolone derivatives. The I1-N1 bond length of 2.069(4) Å is shorter than the one in Zhdankin's reagents or Kiyokawa's reagents, presumably due to the steric hindrance.

  Figure 1

  

  Figure 1.  Single-crystal X-ray diffraction structure of 2a. The thermal ellipsoids are set at 35% probability (CCDC:1909836).

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  To highlight the potential utility of these novel reagents, we attempted to investigate their intrinsic reactivity in organic synthesis. We treated 3-methylbenzo[b]thiophene 3a and 1.0 equiv. of carbazole-containing hypervalent iodine reagent 2c as the model substrates, and the reaction was performed in the presence of 10 mol% CuCl as a catalyst, with dry acetonitrile as solvent at 80 ℃ for 24 h. The desired C—N coupling product 4ac could be obtained in 18% yield (determined by NMR analysis), meanwhile, N—N coupling bicarbazole by-product 5 could be obtained in 52% yield (Table 1, entry 1), presumably via the dimerization of carbazole radical A. Subsequently, the effects of other copper catalysts were examined for the reaction. CuBr or CuTc was found to give bicarbazole product 5 beyond 65% yield and no product 4ac was detected (Table 1, entries 2 and 3). Surprisingly, using Cu(OTf)₂ or (CuOTf)₂C₆H₆ as the catalyst, 4ac was obtained in good yields with trace amount of byproduct 5 (Table 1, entries 4 and 5). And when Cu(CH₃CN)₄PF₆ was used (Table 1, entry 6), product 4ac was formed in a higher yield of 63% (isolated in 58%). Then, a solvent screening showed that switching the solvent from CH₃CN to DCM, DCE, THF or DMSO resulted in lower yield of product 4ac (Table 1, entries 7–10). Additionally, the change of the reaction temperature could not improve the yield of 4ac (Table 1, entries 11 and 12). In particular, the reaction only afforded byproduct 5 in absence of the copper catalyst (Table 1, entry 13).

  Table 1

  

  Table 1.  Optimization of reaction conditions of 3a and 2c.^a

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  With the optimal reaction conditions in hand, the scope of this C—N coupling reaction was explored. As shown in Table 2, diverse carbazole-containing hypervalent iodine reagents were first employed to react with substrate 3a. The products bearing electron-withdrawing groups such as Cl, Br or I at 3, 6-position of carbazole group were obtained in good yields. But the yield of product containing an unsubstituted carbazole group was reduced to 38%, presumably attributed to the less stability of the nonsubstituted carbazole radical. Next, a variety of benzo[b]thiophene derivatives were treated with hypervalent iodine reagent 2c to give C2 substituted benzo[b]thiophene derivates in moderate yields, except 4e in a comparatively lower yield. In addition, thiophene substrates bearing electron-donating groups were also suitable for the reaction to give corresponding C2 carbazole-substituted products. The regio-selectivity presumably results from the denser electron at position 2 than position 3. To further investigate the scope of heterocyclic substrates, 3m and 3n could be respectively transformed to the desired products 4m and 4n in 25% and 26% yield under the standard reaction. Unfortunately, strong electronwithdrawing groups (-CF₃ and -CO₂Et) were not tolerated in the reaction.

  Table 2

  

  Table 2.  Scope of the products 4 from 3 and 2.^a

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  A preliminary study to investigate the mechanism of aforementioned reactions was conducted. Two control experiments were carried out under optimal reaction conditions. When adding 1, 1-diphenylethylene and 2, 2, 6, 6-tetramethyl-1-piperidinyloxy (TEMPO) separately as radical inhibitors into the reaction mixture of 3a and 2c, no desired product 4ac were detected by NMR analysis (Scheme 3). These experimental results and the formation of compound 5 suggested that this reaction might involve a radical process.

  Scheme 3

  

  Scheme 3.  Control experiments.

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  On the basis of our experiment results and the previous reports [12], a plausible reaction mechanism was proposed. As shown in Scheme 4, substrate 3b and reagent 2c were chosen as the model to describe the mechanism. First, the reagent 2c produced a Ncentered carbazole radical A by a Cu(Ⅰ)-mediated single electron transfer (SET) process, simultaneously released a Cu(Ⅱ) species B. Next, the carbazole radical A reacted with 3b generated the radical intermediate C. Finally, the radical intermediate C was oxidized by the Cu(Ⅱ) species B and deprotonated to give desired product 4b, and regenerated a Cu(Ⅰ) species.

  Scheme 4

  

  Scheme 4.  Proposed mechanism.

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  In conclusion, we developed an efficient strategy for the preparation of novel carbazole-containing hypervalent iodine reagents involving N—I bond. These reagents are stable under ambient conditions, and can be used for a direct C—N coupling reaction of aromatic heterocycles and carbazole group. Particularly, a variety of carbazole derivates containing multiple halogen atoms of high interest for organic photoelectric materials can be obtained in one-pot by this method. We believe that these reagents have broad applications in organic synthesis and materials science.

  Acknowledgments

  This work was supported by the National Key Research and Development Program of China (No. 2016YFB0401400), the National Natural Science Foundation of China (Nos. 21302139, 21672120 and 21871158) and the Fok Ying Tong Education Foundation of China (No. 151014).

  
  
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• 

  Scheme 1  Nitrogen-containing benziodoxolone derivatives.

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  Scheme 2  Scope of carbazole-containing hypervalent iodine reagents. Reaction conditions: KF (10 mol%), 1 (4.0 mmol), acetoxybenziodoxolone (4.0 mmol), in dry CH₃CN (10 mL) at room temperature. Isolated yields. ^a10 mmol scale.

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  Figure 1  Single-crystal X-ray diffraction structure of 2a. The thermal ellipsoids are set at 35% probability (CCDC:1909836).

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  Scheme 3  Control experiments.

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  Scheme 4  Proposed mechanism.

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  Table 1.  Optimization of reaction conditions of 3a and 2c.^a

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  Table 2.  Scope of the products 4 from 3 and 2.^a

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•