Abstract
Intermolecular [3 + 2] annulation is one of the most straightforward approaches to construct five membered heterocycles. However, it generally requires the use of functionalized substrates. An ideal reaction approach is to achieve dehydrogenative [3 + 2] annulation under oxidant-free conditions. Here we show an electrooxidative [3 + 2] annulation between phenols and N-acetylindoles under undivided electrolytic conditions. Neither external chemical oxidants nor metal catalysts are required to facilitate the dehydrogenation processes. This reaction protocol provides an environmentally friendly way for the selective synthesis of benzofuroindolines. Various N-acetylindoles bearing different C-3 and C-2 substituents are suitable in this electrochemical transformation, furnishing corresponding benzofuroindolines in up to 99% yield.
Similar content being viewed by others
Introduction
Five-membered heterocycles are highly important structural motifs, which widely exist in natural products, pharmaceuticals, and fundamental materials1,2,3. Intermolecular [3 + 2] annulation are mostly employed approaches to construct five-membered heterocycles. One typical method is 1,3-dipole cycloaddition, which generally requires the use of functionalized substrates such as nitrones, azomethine ylides, azomethine imine, and azides4,5,6,7. To fulfill the demand by green and sustainable chemistry, oxidative [3 + 2] annulation has been gradually developed to pursuit the synthesis of five-membered heterocycles from readily available starting materials8,9,10,11,12. However, external chemical oxidants are often required to facilitate the dehydrogenation processes, which lead to the decreased atom economy of the overall transformation. In addition, using strong chemical oxidants can also cause over-oxidation issues, which makes it difficult to achieve high reaction efficiency. Developing dehydrogenative [3 + 2] annulation under oxidant-free conditions may provide solutions to these problems. Anodic oxidation represents an effective alternative to the oxidation by external chemical oxidants13,14,15,16,17,18,19. Over the past decade, increasing efforts have been made to achieving dehydrogenative cross-coupling under electrochemical conditions20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35.
Benzofuroindoline motifs exist in some important bioactive natural products such as diazonamides36, 37, azonazines38, and phalarine39. The direct oxidative [3 + 2] annulation between phenols and indoles provides a straightforward and atom economic way for the synthesis of benzofuroindolines, which could potentially lead to the formation of two regioisomers. In analogous to the natural bias, the oxidative [3 + 2] annulation between phenols and indoles usually gives benzofuro[2,3-b]indolines. Over the past decade, different reaction protocols for the synthesis of benzofuro[2,3-b]indoline moiety have been developed by Harran37, 40, Danishefsky41, Vincent42, 43, and others44,45,46. In contrast, attempts on phenol–indoles coupling for the synthesis of benzofuro[3,2-b]indolines have rarely succeeded47. In 2014, Vincent and co-workers reported an oxidative [3 + 2] annulation between phenols and 3-substituted N-acetylindoles for the synthesis of benzofuro[3,2]indolines using excess amount of FeCl3 and 2,3-dicyano-5,6-dichlorobenzoquinone, and the reaction yields ranged from 27 to 62% (Fig. 1a)48. It is highly desirable to develop more efficient phenol–indole [3 + 2] annulation for the synthesis of benzofuro[3,2-b]indolines.
Here we present an efficient electrooxidative [3 + 2] annulation between phenols and N-acetylindoles in a simple undivided cell. It enabled the selective synthesis of benzofuro[3,2]indolines under external oxidant- and catalyst-free conditions. Various N-acetylindoles bearing different C-3 substituents are suitable in this electrochemical transformation and can afford corresponding benzofuro[3,2]indolines in up to 99% yield.
Results
Investigation of reaction conditions
We anticipated that electrochemical anodic oxidation might provide a way to achieve external oxidant-free dehydrogenative [3 + 2] annulation (Fig. 1b). p-Methoxylphenol (1a) and 3-methyl-N-acetylindole (2a) were chosen as model substrates to test the reaction conditions. Utilizing nBu4NBF4 as the electrolyte and 1,1,1,3,3,3-hexafluoroisopropyl alcohol (HFIP)/CH2Cl2 as co-solvents, benzofuro[3,2-b]indoline 3a could be obtained in a quantitative yield under 10 mA constant current for 1.8 h in an undivided cell (Table 1, entry 1). Decreased reaction yields were obtained when increasing or decreasing the operating current (Table 1, entries 2 and 3). In addition, solvent effect was also investigated in this transformation. CH2Cl2 was not indispensable for this electrochemical dehydrogenative cross-coupling reaction. A good reaction efficiency could still be achieved when HFIP was used as the sole solvent (Table 1, entry 4). However, HFIP was found to be crucial since no desired product could be obtained when dichloromethane was used solely or HFIP was replaced by methanol (Table 1, entries 5 and 6). As for the electrolyte used, the counter anion had slight effect on the reaction efficiency. nBu4NClO4 and nBu4NPF6 were also suitable in this transformation (Table 1, entries 7 and 8). The effect of the electrode material was also explored. Both replacing graphite rod anode by platinum plate anode and replacing platinum plate cathode by graphite rod cathode led to lower reaction yields (Table 1, entries 9 and 10). However, platinum plate cathode was possible to be replaced by cheap nickel plate cathode for this dehydrogenative [3 + 2] annulation reaction (Table 1, entry 11). Importantly, the reaction could be conducted under atmospheric conditions with a high reaction efficiency (Table 1, entry 12). Obviously, no reaction took place without electric current under air atmosphere (Table 1, entry 13).
Substrate scope
To demonstrate the applicability of this transformation, we first turned to explore the substrate scope for the synthesis of benzofuro[3,2-b]indolines (Fig. 2). The reaction between p-methoxylphenol and N-acyl indoles bearing different C-3 substituents such as simple alkyl, functionalized alkyl, allyl and phenyl groups were all suitable in this dehydrogenative [3 + 2] annulation reaction, affording corresponding benzofuro[3,2-b]indolines in good to excellent yields (3a–3f). N-acetylindoles bearing electron neutral substituents such as methyl group and chloride at C-5 or C-6 position also showed good reactivity in the synthesis of benzofuro[3,2-b]indolines (3g–3i). Strong electron-withdrawing trifluoromethyl group at the C-5 position led to a decreased reaction yield (3j). Strong electron-donating groups at C-5 or C-6 position were not tolerated under the electrochemical conditions. In the next step, efforts were also taken to test the scope of phenols. Alkoxy substituents at the ortho or para position of phenols were essential for achieving good reaction efficiency. Electron neutral phenols showed decreased reactivity under the standard conditions. p-Methoxyphenol bearing a bulky tert-butyl group at the C-2 position was still able to synthesize benzofuro[3,2-b]indoline in a good yield (3k). Ortho-halide substituents including Cl and Br were well tolerated in the synthesis of benzofuro[3,2-b]indolines (3l and 3m). Phenols bearing methoxyl group at the ortho position or bearing ethoxyl group at the para position both afforded the desired products in good yields (3n and 3o). Electron-rich 4-methoxynaphtol could also afford the desired benzofuroindoline 3p in 35% yield.
Besides 3-substituted N-acetylindoles, 2-substituted N-acetylindoles were also applied as substrates in this transformation (Fig. 3). Under the standard conditions, the reaction between p-methoxylphenol and 2-methyl-N-acetylindole selectively furnished benzofuro[2,3-b]indoline 4a. Similarly, the reactions of other 2-substituted N-acetylindoles with p-methoxylphenol were only able to give benzofuro[2,3-b]indolines (4b–4e). Moreover, 2,3-disubstituted N-acetylindoles were also able to participate in the electrooxidative [3 + 2] annulation reaction for the synthesis of benzofuro[2,3-b]indolines (4f–4g).
It has been noted that coordination of Lewis acid with N-acetyl indoles can change the classical polarity of the C2 and C3-positions on indoles49. In order to access benzofuro[3,2-b]indolines, we have tried to add Lewis acids into the electrooxidative [3 + 2] annulation reaction with 2-substituted N-acetylindoles and 2,3-disubstituted N-acetylindoles. By adding 2 equiv. of ZnCl2, 26% of benzofuro[3,2-b]indoline 3q could be obtained from the reaction between 2,3-dimethyl-N-acetylindole and p-methoxylphenol (Fig. 4a). Similarly, the reaction between 2,3-dimethyl-N-acetylindole and p-methoxylphenol furnished corresponding benzofuro[3,2-b]indoline in 25% yield by adding 2 equiv. of ZnCl2 (Fig. 4b). However, the reaction selectivity with 2-substituted N-acetylindoles could not be tuned to benzofuro[3,2-b]indolines even by adding Lewis acids.
The scalability of this electrooxidative [3 + 2] annulation was then evaluated by performing a 5.0 mmol scale reaction. Under atmospheric conditions, the gram scale reaction between 1a and 2a afforded the corresponding benzofuro[3,2-b]indoline 3a in a high reaction efficiency with a 87% yield (Figs. 5 and 3a, 1.3 g). This result demonstrated the great potential of this electrooxidative [3 + 2] annulation in future application.
Discussion
To get some insight into the electron transfer processes, cyclic voltammetry experiments of phenols and N-acetylindoles were conducted. As shown in Fig. 6a, an obvious oxidation peak of p-methoxylphenol could be observed at 1.16 V while no obvious oxidation peak of p-methylphenol and p-trifluoromethylphenol could be observed in their cyclic voltammograms. Cyclic voltammograms of N-acetylindoles with different electron density were also presented. Oxidation peaks of 3-methyl-5-methoxyl-N-acetylindole were observed above 0.98 V while oxidation peaks of 3-methyl-N-acetylindole and 3-methyl-5-trifluoromethyl-N-acetylindole were observed at 1.10 V and 1.15 V, respectively (Fig. 6b). Interestingly, the oxidation potential of p-methoxylphenol was quite close to 3-methyl-N-acetylindole and 3-methyl-5-trifluoromethyl-N-acetylindole. Therefore, the oxidation of both substrates was possible under the electrolytic conditions.
Since both of the substrates were possible to be oxidized by the anode, a radical trapping experiment by triethyl phosphite was conducted to explore the existence of radical intermediates (Fig. 7). No desired benzofuro[3,2-b]indoline could be observed. Instead, an indole phosphorylation product 5a could be obtained in 48% yield. These results indicated that the reaction might go through a radical mechanism and indole cation radical intermediate was likely to be generated during electrolysis. It has been reported that radical cations of aromatic compounds (ArH•+) generated in HFIP are extremely persistent50,51,52. According to the persistent radical effect, the radical coupling between a persistent radical and a transient radical would lead to selective bond formation53. The indole cation radical could be considered as a persistent radical while phenoxy radical was a transient radical. Thus, the coupling of the indole cation radical and the phenoxy radical was possible to be involved for this transformation.
Based on the experimental results and previous reports10, 48, a plausible reaction mechanism between 1a and 2a is presented in Fig. 8. A single-electron-transfer oxidation of p-methoxylphenol by anodic oxidation generates a phenol oxygen radical I. The oxygen raidcal I can be isomerized to carbon radical II 22. At the same time, N-acetylindole can also be oxidized by the anode to afford cation radical intermediate III. Direct cross-coupling of carbon radical II with cation radical intermediate III will form cation intermediate IV. Following intramolecular cyclization and deprotonation of IV will generate benzofuro[3,2-b]indoline 3a. Meanwhile, HFIP is reduced at the Pt cathode to afford hydrogen gas.
In summary, we have developed a green and efficient electrooxidative [3 + 2] annulation between phenols and N-acetylindoles. This reaction protocol avoids the use of external chemical oxidants and H2 is the only byproduct. Under undivided electrolytic conditions, a series of benzofuro[3,2-b]indolines can be obtained in good to excellent yields. Significantly, this reaction can be conducted in gram scale under atmospheric conditions. Mechanistically, both phenol and N-acetylindole are considered to be oxidized by anode to generate radical intermediates during the reaction. In this reaction case, electrochemical external oxidant-free dehydrogenative cross-coupling demonstrated higher reaction efficiency than traditional oxidative cross-coupling protocol, which may inspire people to use electrochemical methods in more oxidative cross-coupling reactions.
Methods
Representative procedure for the synthesis of benzofuro[3,2-b]indoline (3a)
In an oven-dried undivided three-necked bottle (25 ml) equipped with a stir bar, p-methoxylphenol (24.8 mg, 0.20 mmol), 3-methyl-N-acetylindole (51.9 mg, 0.30 mmol), nBu4NBF4 (65.8 mg, 0.20 mmol), and HFIP/CH2Cl2 (6.0 ml/4.0 ml) were combined and added. The bottle was equipped with graphite rod (ϕ 6 mm, about 10 mm immersion depth in solution) as the anode and platinum plate (15 mm × 15 mm × 0.3 mm) as the cathode and then charged with nitrogen. The reaction mixture was stirred and electrolyzed at a constant current of 10 mA (j ≈ 16 mA/cm2) under room temperature for 1.8 h. When the reaction finished, the reaction mixture was washed with water and extracted with CH2Cl2 (10 ml × 3). The organic layers were combined, dried over Na2SO4, and concentrated. The pure product was obtained by flash column chromatography on silica gel (hexane: ethyl acetate = 10:1). Yellow oil was obtained in 99% isolated yield. Since the acetyl group could form intramolecular hydrogen bonds with the hydrogens adjacent to nitrogen atom, the spectra demonstrate a mixture of rotamers (74:26). 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 7.6 Hz, 0.3H), 7.55–7.48 (d, J = 7.6 Hz, 0.7H), 7.44 (d, J = 6.8 Hz, 0.3H) 7.30 (t, J = 7.6 Hz, 1.7H), 7.12 (t, J = 7.3 Hz, 1.7H), 6.93 (s, 0.3H), 6.83–6.57 (m, 2H), 5.96 (s, 0.7H), 5.61 (s, 0.3H), 3.73 (s, 3H), 2.57(s, 0.8H), 2.49 (s, 2.2H), 1.82 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 168.71, 167.98, 154.36, 152.97, 152.84, 141.09, 140.35, 135.01, 133.68, 129.93, 126.94, 126.02, 125.02, 124.85, 124.01, 123.44, 118.08, 116.89, 116.11, 114.47, 112.45, 111.02, 110.19, 92.79, 90.60, 72.38, 71.83, 55.99, 25.04, 24.80, 24.27. For 1H NMR, 13C NMR, 19F NMR and 31P NMR (if applicable) spectra of compounds 3a–3r, 4a–4g, 5a, see Supplementary Figs. 1–54. For the general information of the analytical methods and procedure for cyclic voltammetry please see Supplementary Methods.
Procedure for gram scale synthesis of 3a
In an oven-dried conical flask (100 ml) equipped with a stir bar, 4-methoxyphenol (0.62 g, 5.0 mmol), 3-methyl-N-acetylindole (1.3 g, 7.5 mmol), nBu4NBF4 (1.3 g, 4.0 mmol), and HFIP/CH2Cl2 (60 ml/40 ml) were combined and added. The bottle was equipped with graphite rod (ϕ 6 mm, about 10 mm immersion depth in solution) as the anode and platinum plate (15 mm × 15 mm × 0.3 mm) as the cathode. The reaction mixture was stirred and electrolyzed at a constant current of 50 mA (j anode ≈ 83 mA/cm2) under air atmosphere at room temperature for 10 h (3.7 F). When the reaction finished, the reaction mixture was washed with water and extracted with CH2Cl2 (100 ml × 3). The organic layers were combined, dried over Na2SO4, and concentrated. The pure product was obtained by flash column chromatography on silica gel (hexane: ethyl acetate = 10:1). Yellow oil was obtained in 87% isolated yield (1.3 g). For the experimental setup diagram for the gram scale reaction see Supplementary Fig. 55.
Data availability
The authors declare that the data supporting the findings of this study are available within the article and its Supplementary Information files.
References
Bambas, L. L. Five-Membered Heterocyclic Compounds with Nitrogen and Sulfur or Nitrogen, Sulfur, and Oxygen (Except Thiazole) (Interscience Publishers, 1952).
Eicher, T., Hauptmann, S. & Speicher, A. The Chemistry of Heterocycles: Structure, Reactions, Syntheses, and Applications, 3rd edn (Wiley-VCH, 2012).
Katritzky, A. R. Introduction: heterocycles. Chem. Rev. 104, 2125–2126 (2004).
Pandey, G., Banerjee, P. & Gadre, S. R. Construction of enantiopure pyrrolidine ring system via asymmetric [3+2]-cycloaddition of azomethine ylides. Chem. Rev. 106, 4484–4517 (2006).
Stanley, L. M. & Sibi, M. P. Enantioselective copper-catalyzed 1,3-dipolar cycloadditions. Chem. Rev. 108, 2887–2902 (2008).
Amblard, F., Cho, J. H. & Schinazi, R. F. Cu(I)-catalyzed Huisgen azide−alkyne 1,3-dipolar cycloaddition reaction in nucleoside, nucleotide, and oligonucleotide chemistry. Chem. Rev. 109, 4207–4220 (2009).
Hashimoto, T. & Maruoka, K. Recent advances of catalytic asymmetric 1,3-dipolar cycloadditions. Chem. Rev. 115, 5366–5412 (2015).
Stuart, D. R., Bertrand-Laperle, M., Burgess, K. M. N. & Fagnou, K. Indole synthesis via rhodium catalyzed oxidative coupling of acetanilides and internal alkynes. J. Am. Chem. Soc. 130, 16474–16475 (2008).
He, C. et al. Silver-mediated oxidative C–H/C–H functionalization: a strategy to construct polysubstituted furans. J. Am. Chem. Soc. 134, 5766–5769 (2012).
Huang, Z. et al. Iron-catalyzed oxidative radical cross-coupling/cyclization between phenols and olefins. Angew. Chem. Int. Ed. 52, 7151–7155 (2013).
Kuram, M. R., Bhanuchandra, M. & Sahoo, A. K. Direct access to benzo[b]furans through palladium-catalyzed oxidative annulation of phenols and unactivated internal alkynes. Angew. Chem. Int. Ed. 52, 4607–4612 (2013).
Tang, S. et al. Iodine-catalyzed radical oxidative annulation for the construction of dihydrofurans and indolizines. Org. Lett. 17, 2404–2407 (2015).
Schäfer, H. J. Contributions of organic electrosynthesis to green chemistry. C. R. Chim. 14, 745–765 (2011).
Frontana-Uribe, B. A., Little, R. D., Ibanez, J. G., Palma, A. & Vasquez-Medrano, R. Organic electrosynthesis: a promising green methodology in organic chemistry. Green Chem. 12, 2099–2119 (2010).
Yoshida, J.-I., Kataoka, K., Horcajada, R. & Nagaki, A. Modern strategies in electroorganic synthesis. Chem. Rev. 108, 2265–2299 (2008).
Francke, R. & Little, R. D. Redox catalysis in organic electrosynthesis: basic principles and recent developments. Chem. Soc. Rev. 43, 2492–2521 (2014).
Sperry, J. B. & Wright, D. L. The application of cathodic reductions and anodic oxidations in the synthesis of complex molecules. Chem. Soc. Rev. 35, 605–621 (2006).
Francke, R. Recent advances in the electrochemical construction of heterocycles. Beilstein J. Org. Chem. 10, 2858–2873 (2014).
Horn, E. J., Rosen, B. R. & Baran, P. S. Synthetic organic electrochemistry: an enabling and innately sustainable method. ACS Cent. Sci. 2, 302–308 (2016).
Amatore, C., Cammoun, C. & Jutand, A. Electrochemical recycling of benzoquinone in the Pd/benzoquinone-catalyzed Heck-type reactions from arenes. Adv. Synth. Catal. 349, 292–296 (2007).
Kirste, A., Schnakenburg, G., Stecker, F., Fischer, A. & Waldvogel, S. R. Anodic phenol–arene cross-coupling reaction on boron-doped diamond electrodes. Angew. Chem. Int. Ed. 49, 971–975 (2010).
Kirste, A., Elsler, B., Schnakenburg, G. & Waldvogel, S. R. Efficient anodic and direct phenol–arene C,C cross-coupling: the benign role of water or methanol. J. Am. Chem. Soc. 134, 3571–3576 (2012).
Elsler, B., Schollmeyer, D., Dyballa, K. M., Franke, R. & Waldvogel, S. R. Metal- and reagent-free highly selective anodic cross-coupling reaction of phenols. Angew. Chem. Int. Ed. 53, 5210–5213 (2014).
Morofuji, T., Shimizu, A. & Yoshida, J.-I. Metal- and chemical-oxidant-free C-H/C-H cross-coupling of aromatic compounds: the use of radical-cation pools. Angew. Chem. Int. Ed. 51, 7259–7262 (2012).
Gao, W.-J. et al. Electrochemically initiated oxidative amination of benzoxazoles using tetraalkylammonium halides as redox catalysts. J. Org. Chem. 79, 9613–9618 (2014).
Lips, S. et al. Synthesis of meta-terphenyl-2,2′′-diols by anodic C−C cross-coupling reactions. Angew. Chem. Int. Ed. 55, 10872–10876 (2016).
Hou, Z.-W. et al. Electrochemical C−H/N−H functionalization for the synthesis of highly functionalized (Aza)indoles. Angew. Chem. Int. Ed. 55, 9168–9172 (2016).
Hayashi, R., Shimizu, A. & Yoshida, J.-I. The stabilized cation pool method: metal- and oxidant-free benzylic C–H/aromatic C–H cross-coupling. J. Am. Chem. Soc. 138, 8400–8403 (2016).
Qian, X.-Y., Li, S.-Q., Song, J. & Xu, H.-C. TEMPO-catalyzed electrochemical C–H thiolation: synthesis of benzothiazoles and thiazolopyridines from thioamides. ACS Catal. 7, 2730–2734 (2017).
Wu, Z.-J. & Xu, H.-C. Synthesis of C3-fluorinated oxindoles through reagent-free cross-dehydrogenative coupling. Angew. Chem. Int. Ed. 56, 4734–4738 (2017).
Zhao, H.-B. et al. Amidinyl radical formation through anodic N−H bond cleavage and its application in aromatic C−H bond functionalization. Angew. Chem. Int. Ed. 56, 587–590 (2017).
Xiong, P., Xu, H.-H. & Xu, H.-C. Metal- and reagent-free intramolecular oxidative amination of tri- and tetrasubstituted alkenes. J. Am. Chem. Soc. 139, 2956–2959 (2017).
Wang, P., Tang, S. & Lei, A. Electrochemical intramolecular dehydrogenative C-S bond formation for the synthesis of benzothiazoles. Green Chem. 19, 2092–2095 (2017).
Wang, P., Tang, S., Huang, P. & Lei, A. Electrochemical oxidant-free dehydrogenative C−H/S−H cross-coupling. Angew. Chem. Int. Ed. 56, 3009–3013 (2017).
Tang, S., Gao, X. & Lei, A. Electrochemical intramolecular oxidative annulation of N-aryl enamines into substituted indoles mediated by iodides. Chem. Commun. 53, 3354–3356 (2017).
Li, J., Burgett, A. W. G., Esser, L., Amezcua, C. & Harran, P. G. Total synthesis of nominal diazonamides—Part 2: on the true structure and origin of natural isolates. Angew. Chem. Int. Ed. 40, 4770–4773 (2001).
Burgett, A. W. G., Li, Q., Wei, Q. & Harran, P. G. A concise and flexible total synthesis of (−)-diazonamide A. Angew. Chem. Int. Ed. 42, 4961–4966 (2003).
Wu, Q.-X. et al. Azonazine, a novel dipeptide from a hawaiian marine sediment-derived fungus, Aspergillus insulicola. Org. Lett. 12, 4458–4461 (2010).
Cockrum, P. A. et al. (−)-Phalarine, a furanobisindole alkaloid from phalariscoerulescens. Phytochemistry 51, 153–157 (1999).
Ding, H. et al. Electrolytic macrocyclizations: scalable synthesis of a diazonamide-based drug development candidate. Angew. Chem. Int. Ed. 54, 4818–4822 (2015).
Chan, C., Li, C., Zhang, F. & Danishefsky, S. J. Studies toward the total synthesis of phalarine: a survey of some biomimetic possibilities. Tetrahedron Lett. 47, 4839–4841 (2006).
Beaud, R., Guillot, R., Kouklovsky, C. & Vincent, G. FeCl3-mediated friedel–crafts hydroarylation with electrophilic N-acetyl indoles for the synthesis of benzofuroindolines. Angew. Chem. Int. Ed. 51, 12546–12550 (2012).
Denizot, N. et al. Bioinspired direct access to benzofuroindolines by oxidative [3+2] annulation of phenols and indoles. Org. Lett. 16, 5752–5755 (2014).
Tian, W., Chennamaneni, L. R., Suzuki, T. & Chen, D. Y. K. A second-generation formal synthesis of (+)-haplophytine. Eur. J. Org. Chem. 2011, 1027–1031 (2011).
Zhao, J.-C., Yu, S.-M., Liu, Y. & Yao, Z.-J. Biomimetic synthesis of ent-(−)-azonazine and stereochemical reassignment of natural product. Org. Lett. 15, 4300–4303 (2013).
Liao, L. et al. Highly enantioselective [3+2] coupling of indoles with quinone monoimines promoted by a chiral phosphoric acid. Angew. Chem. Int. Ed. 53, 10471–10475 (2014).
Li, C., Chan, C., Heimann, A. C. & Danishefsky, S. J. On the rearrangement of an azaspiroindolenine to a precursor to phalarine: mechanistic insights. Angew. Chem. Int. Ed. 46, 1444–1447 (2007).
Tomakinian, T., Guillot, R., Kouklovsky, C. & Vincent, G. Direct oxidative coupling of N-acetyl indoles and phenols for the synthesis of benzofuroindolines related to phalarine. Angew. Chem. Int. Ed. 53, 11881–11885 (2014).
Marques, A.-S., Coeffard, V., Chataigner, I., Vincent, G. & Moreau, X. Iron-mediated domino interrupted Iso-Nazarov/dearomative (3+2)-cycloaddition of electrophilic indoles. Org. Lett. 18, 5296–5299 (2016).
Eberson, L., Hartshorn, M. P. & Persson, O. 1,1,1,3,3,3-Hexafluoropropan-2-ol as a solvent for the generation of highly persistent radical cations. J. Chem. Soc. 2, 1735–1744 (1995).
Eberson, L., Persson, O. & Hartshorn, M. P. Detection and reactions of radical cations generated by photolysis of aromatic compounds with tetranitromethane in 1,1,1,3,3,3-hexafluoro-2-propanol at room temperature. Angew. Chem. Int. Ed. 34, 2268–2269 (1995).
Eberson, L., Hartshorn, M. P. & Persson, O. Generation of solutions of highly persistent radical cations by 4-tolylthallium(III) bis(trifluoroacetate) in 1,1,1,3,3,3-hexafluoropropan-2-ol. J. Chem. Soc. Chem. Commun. 0, 1131–1132 (1995).
Fischer, H. The persistent radical effect: a principle for selective radical reactions and living radical polymerizations. Chem. Rev. 101, 3581–3610 (2001).
Acknowledgements
This work was supported by the National Natural Science Foundation of China (21390400, 21520102003, 21272180 and 21302148), the Hubei Province Natural Science Foundation of China (2013CFA081), the Research Fund for the Doctoral Program of Higher Education of China (20120141130002), and the Ministry of Science and Technology of China (2012YQ120060). The Program of Introducing Talents of Discipline to Universities of China (111 Program) is also appreciated.
Author information
Authors and Affiliations
Contributions
K.L. and S.T. contributed equally to this work. A.L. and S.T. contributed to the conception and design of the experiments. K.L., S.T., and P.H. performed the experiments. S.T. and A.L. co-wrote the manuscript and all authors contributed to data analysis and scientific discussion.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Additional information
Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Liu, K., Tang, S., Huang, P. et al. External oxidant-free electrooxidative [3 + 2] annulation between phenol and indole derivatives. Nat Commun 8, 775 (2017). https://doi.org/10.1038/s41467-017-00873-1
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41467-017-00873-1
This article is cited by
-
Enantioselective synthesis of atropisomeric indoles via iron-catalysed oxidative cross-coupling
Nature Chemistry (2023)
-
Electrochemically time-dependent oxidative coupling/coupling-cyclization reaction between heterocycles: tunable synthesis of polycyclic indole derivatives with fluorescence properties
Science China Chemistry (2022)
-
Electrooxidation enables highly regioselective dearomative annulation of indole and benzofuran derivatives
Nature Communications (2020)
-
Electrochemical synthesis of AuPt nanoflowers in deep eutectic solvent at low temperature and their application in organic electro-oxidation
Scientific Reports (2018)
-
Dehydrogenative reagent-free annulation of alkenes with diols for the synthesis of saturated O-heterocycles
Nature Communications (2018)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.