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Organocatalytic enantioselective functionalization of indoles in the carbocyclic ring with cyclic imines

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Organocatalytic enantioselective functionalization of indoles in the carbocyclic ring with cyclic imines

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Vila, C.; Tortosa, A.; Blay, G.; Muñoz Roca, MDC.; Pedro, J. (2019). Organocatalytic enantioselective functionalization of indoles in the carbocyclic ring with cyclic imines. New Journal of Chemistry. 43(1):130-134. https://doi.org/10.1039/c8nj05577g

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Title: Organocatalytic enantioselective functionalization of indoles in the carbocyclic ring with cyclic imines
Author: Vila, C. Tortosa, A. Blay, G. Muñoz Roca, María Del Carmen Pedro, J.R.
UPV Unit: Universitat Politècnica de València. Departamento de Física Aplicada - Departament de Física Aplicada
Issued date:
[EN] An organocatalytic enantioselective functionalization in the carbocyclic ring of indoles with benzoxathiazine 2,2-dioxides is described using a quinine-derived bifunctional organocatalyst. This aza-Friedel-Crafts ...[+]
Subjects: Friedel-Crafts reaction , Asymmetric-Synthesis , Alkylation , Ketimines , Hydroxyindoles , Construction , Derivatives , Inhibitors
Copyrigths: Reserva de todos los derechos
New Journal of Chemistry. (issn: 1144-0546 )
DOI: 10.1039/c8nj05577g
The Royal Society of Chemistry
Publisher version: https://doi.org/10.1039/c8nj05577g
Project ID:
Financial support from the Agencia Estatal de Investigación (AEI, Spanish Government) and Fondo Europeo de Desarrollo Regional (FEDER, European Union) (CTQ2017-84900-P) is acknowledged. C. V. thanks the Spanish Government ...[+]
Type: Artículo


Friedel–Crafts Chemistry , ed. G. A. Olah , Wiley , New York , 1973

Catalytic Asymmetric Friedel–Crafts Alkylations , ed. M. Bandini and A. Umani-Ronchi , Wiley-VCH , Weinheim , 2009

Poulsen, T. B., & Jørgensen, K. A. (2008). Catalytic Asymmetric Friedel−Crafts Alkylation ReactionsCopper Showed the Way. Chemical Reviews, 108(8), 2903-2915. doi:10.1021/cr078372e [+]
Friedel–Crafts Chemistry , ed. G. A. Olah , Wiley , New York , 1973

Catalytic Asymmetric Friedel–Crafts Alkylations , ed. M. Bandini and A. Umani-Ronchi , Wiley-VCH , Weinheim , 2009

Poulsen, T. B., & Jørgensen, K. A. (2008). Catalytic Asymmetric Friedel−Crafts Alkylation ReactionsCopper Showed the Way. Chemical Reviews, 108(8), 2903-2915. doi:10.1021/cr078372e

Terrasson, V., Marcia de Figueiredo, R., & Campagne, J. M. (2010). Organocatalyzed Asymmetric Friedel-Crafts Reactions. European Journal of Organic Chemistry, 2010(14), 2635-2655. doi:10.1002/ejoc.200901492

Bandini, M., & Eichholzer, A. (2009). Catalytic Functionalization of Indoles in a New Dimension. Angewandte Chemie International Edition, 48(51), 9608-9644. doi:10.1002/anie.200901843

Bartoli, G., Bencivenni, G., & Dalpozzo, R. (2010). Organocatalytic strategies for the asymmetric functionalization of indoles. Chemical Society Reviews, 39(11), 4449. doi:10.1039/b923063g

Marques-Lopez, E., Diez-Martinez, A., Merino, P., & Herrera, R. (2009). The Role of the Indole in Important Organocatalytic Enantioselective Friedel-Crafts Alkylation Reactions. Current Organic Chemistry, 13(16), 1585-1609. doi:10.2174/138527209789578126

You, S.-L., Cai, Q., & Zeng, M. (2009). Chiral Brønsted acid catalyzed Friedel–Crafts alkylation reactions. Chemical Society Reviews, 38(8), 2190. doi:10.1039/b817310a

Chiral Amine Synthesis: Methods, Developments and Applications , ed. T. C. Nugent , Wiley-VCH , Weinheim , 2010

Chen, Y., & Xie, Z. (2012). Research Progress in Friedel-Crafts Reaction of Indoles and Imines. Chinese Journal of Organic Chemistry, 32(03), 462. doi:10.6023/cjoc1103201

Hatano, M., Mochizuki, T., Nishikawa, K., & Ishihara, K. (2017). Enantioselective Aza-Friedel–Crafts Reaction of Indoles with Ketimines Catalyzed by Chiral Potassium Binaphthyldisulfonates. ACS Catalysis, 8(1), 349-353. doi:10.1021/acscatal.7b03708

Wang, Y.-Q., Song, J., Hong, R., Li, H., & Deng, L. (2006). Asymmetric Friedel−Crafts Reaction of Indoles with Imines by an Organic Catalyst. Journal of the American Chemical Society, 128(25), 8156-8157. doi:10.1021/ja062700v

Kang, Q., Zhao, Z.-A., & You, S.-L. (2007). Highly Enantioselective Friedel−Crafts Reaction of Indoles with Imines by a Chiral Phosphoric Acid. Journal of the American Chemical Society, 129(6), 1484-1485. doi:10.1021/ja067417a

Rowland, G. B., Rowland, E. B., Liang, Y., Perman, J. A., & Antilla, J. C. (2007). The Highly Enantioselective Addition of Indoles toN-Acyl Imines with Use of a Chiral Phosphoric Acid Catalyst. Organic Letters, 9(14), 2609-2611. doi:10.1021/ol0703579

Zhang, G., Wang, L., Nie, J., & Ma, J. (2008). Chiral Brønsted Acid‐Mediated Enantioselective Organocatalytic Three‐Component Reaction for the Construction of Trifluoromethyl‐Containing Molecules. Advanced Synthesis & Catalysis, 350(10), 1457-1463. doi:10.1002/adsc.200800239

Jia, Y.-X., Xie, J.-H., Duan, H.-F., Wang, L.-X., & Zhou, Q.-L. (2006). Asymmetric Friedel−Crafts Addition of Indoles toN-Sulfonyl Aldimines:  A Simple Approach to Optically Active 3-Indolyl-methanamine Derivatives. Organic Letters, 8(8), 1621-1624. doi:10.1021/ol0602001

Arai, T., & Kakino, J. (2016). Catalytic Asymmetric Synthesis of 3-Indolyl Methanamines Using Unprotected Indoles and N-Boc Imines under Basic Conditions. Angewandte Chemie International Edition, 55(49), 15263-15267. doi:10.1002/anie.201607679

Wu, K., Jiang, Y.-J., Fan, Y.-S., Sha, D., & Zhang, S. (2012). Double Axially Chiral Bisphosphorylimides Catalyzed Highly Enantioselective and Efficient Friedel-Crafts Reaction of Indoles with Imines. Chemistry - A European Journal, 19(2), 474-478. doi:10.1002/chem.201202900

Xu, F., Huang, D., Han, C., Shen, W., Lin, X., & Wang, Y. (2010). SPINOL-Derived Phosphoric Acids: Synthesis and Application in Enantioselective Friedel−Crafts Reaction of Indoles with Imines. The Journal of Organic Chemistry, 75(24), 8677-8680. doi:10.1021/jo101640z

Qian, Y., Ma, G., Lv, A., Zhu, H.-L., Zhao, J., & Rawal, V. H. (2010). Squaramide-catalyzed enantioselective Friedel–Crafts reaction of indoles with imines. Chemical Communications, 46(17), 3004. doi:10.1039/b922120d

Kang, Q., Zhao, Z.-A., & You, S.-L. (2009). Enantioselective synthesis of (3-indolyl)glycine derivatives via asymmetric Friedel–Crafts reaction between indoles and glyoxylate imines. Tetrahedron, 65(8), 1603-1607. doi:10.1016/j.tet.2008.12.061

Johannsen, M. (1999). An enantioselective synthesis of heteroaromatic N-tosyl α-amino acids. Chemical Communications, (21), 2233-2234. doi:10.1039/a906758b

Husmann, R., Sugiono, E., Mersmann, S., Raabe, G., Rueping, M., & Bolm, C. (2011). Enantioselective Organocatalytic Synthesis of Quaternary α-Amino Acids Bearing a CF3Moiety. Organic Letters, 13(5), 1044-1047. doi:10.1021/ol103093r

Feng, J., Yan, W., Wang, D., Li, P., Sun, Q., & Wang, R. (2012). The highly enantioselective addition of indoles and pyrroles to isatins-derived N-Boc ketimines catalyzed by chiral phosphoric acids. Chemical Communications, 48(64), 8003. doi:10.1039/c2cc33200k

Yu, P., He, J., & Guo, C. (2008). 9-Thiourea Cinchona alkaloid supported on mesoporous silica as a highly enantioselective, recyclable heterogeneous asymmetric catalyst. Chemical Communications, (20), 2355. doi:10.1039/b800640g

Osorio-Planes, L., Rodríguez-Escrich, C., & Pericàs, M. A. (2014). Enantioselective Continuous-Flow Production of 3-Indolylmethanamines Mediated by an Immobilized Phosphoric Acid Catalyst. Chemistry - A European Journal, 20(8), 2367-2372. doi:10.1002/chem.201303860

Chen, L.-Y., He, H., Chan, W.-H., & Lee, A. W. M. (2011). Chiral Sulfonimide as a Brønsted Acid Organocatalyst for Asymmetric Friedel–Crafts Alkylation of Indoles with Imines. The Journal of Organic Chemistry, 76(17), 7141-7147. doi:10.1021/jo2011335

Wang, Y., Jiang, L., Li, L., Dai, J., Xiong, D., & Shao, Z. (2016). An Arylation Strategy to Propargylamines: Catalytic Asymmetric Friedel-Crafts-type Arylation Reactions of C-Alkynyl Imines. Angewandte Chemie International Edition, 55(48), 15142-15146. doi:10.1002/anie.201608918

Wang, X.-W., Hua, Y.-Z., & Wang, M.-C. (2016). Synthesis of 3-Indolylglycine Derivatives via Dinuclear Zinc Catalytic Asymmetric Friedel–Crafts Alkylation Reaction. The Journal of Organic Chemistry, 81(19), 9227-9234. doi:10.1021/acs.joc.6b01805

Zhang, X., Zhang, J., Lin, L., Zheng, H., Wu, W., Liu, X., & Feng, X. (2016). Chiral N,N′ -Dioxide-Zinc(II) Complex-Catalyzed Asymmetric Aza-Friedel-Crafts Reaction of Isatin-Derived Ketimines with Indoles. Advanced Synthesis & Catalysis, 358(19), 3021-3026. doi:10.1002/adsc.201600630

R. J. Sundberg , Indoles , Academic Press , San Diego , 1996

S. M. Bronner , G. Y. J.Im and N. K.Garg , Heterocycles in Natural Product Synthesis , Wiley-VCH , Weinhem , 2011 , p. 221

Kang, Q., Zheng, X.-J., & You, S.-L. (2008). Highly Enantioselective Friedel–Crafts Reaction of 4,7-Dihydroindoles with Imines by Chiral Phosphoric Acids: Facile Access to 2-Indolyl Methanamine Derivatives. Chemistry - A European Journal, 14(12), 3539-3542. doi:10.1002/chem.200800263

Huang, B.-B., Wu, L., Liu, R.-R., Xing, L.-L., Liang, R.-X., & Jia, Y.-X. (2018). Enantioselective Friedel–Crafts C2-alkylation of 3-substituted indoles with trifluoropyruvates and cyclic N-sulfonyl α-ketiminoesters. Organic Chemistry Frontiers, 5(6), 929-932. doi:10.1039/c7qo01014a

Sandtorv, A. H. (2015). Transition Metal-Catalyzed CH Activation of Indoles. Advanced Synthesis & Catalysis, 357(11), 2403-2435. doi:10.1002/adsc.201500374

Leitch, J. A., Bhonoah, Y., & Frost, C. G. (2017). Beyond C2 and C3: Transition-Metal-Catalyzed C–H Functionalization of Indole. ACS Catalysis, 7(9), 5618-5627. doi:10.1021/acscatal.7b01785

Montesinos-Magraner, M., Vila, C., Rendón-Patiño, A., Blay, G., Fernández, I., Muñoz, M. C., & Pedro, J. R. (2016). Organocatalytic Enantioselective Friedel–Crafts Aminoalkylation of Indoles in the Carbocyclic Ring. ACS Catalysis, 6(4), 2689-2693. doi:10.1021/acscatal.6b00260

Montesinos-Magraner, M., Vila, C., Blay, G., Fernández, I., Muñoz, M. C., & Pedro, J. R. (2017). Hydroxy-Directed Enantioselective Hydroxyalkylation in the Carbocyclic Ring of Indoles. Organic Letters, 19(7), 1546-1549. doi:10.1021/acs.orglett.7b00354

Vila, C., Rostoll-Berenguer, J., Sánchez-García, R., Blay, G., Fernández, I., Muñoz, M. C., & Pedro, J. R. (2018). Enantioselective Synthesis of 2-Amino-1,1-diarylalkanes Bearing a Carbocyclic Ring Substituted Indole through Asymmetric Catalytic Reaction of Hydroxyindoles with Nitroalkenes. The Journal of Organic Chemistry, 83(12), 6397-6407. doi:10.1021/acs.joc.8b00612

Poulsen, P. H., Feu, K. S., Paz, B. M., Jensen, F., & Jørgensen, K. A. (2015). Organocatalytic Asymmetric 1,6-Addition/1,4-Addition Sequence to 2,4-Dienals for the Synthesis of Chiral Chromans. Angewandte Chemie International Edition, 54(28), 8203-8207. doi:10.1002/anie.201503370

Xiao, M., Xu, D., Liang, W., Wu, W., Chan, A. S. C., & Zhao, J. (2017). Organocatalytic Enantioselective Friedel-Crafts Alkylation/Lactonization Reaction of Hydroxyindoles with Methyleneoxindoles. Advanced Synthesis & Catalysis, 360(5), 917-924. doi:10.1002/adsc.201701089

Xun, W., Xu, B., Chen, B., Meng, S., Chan, A. S. C., Qiu, F. G., & Zhao, J. (2018). Regio and Enantioselective Organocatalytic Friedel–Crafts Alkylation of 4-Aminoindoles at the C7-Position. Organic Letters, 20(3), 590-593. doi:10.1021/acs.orglett.7b03703

Liu, J.-Y., Yang, X.-C., Lu, H., Gu, Y.-C., & Xu, P.-F. (2018). Organocatalytic, Enantioselective Friedel–Crafts Reaction of Indoles in the Carbocyclic Ring and Electron-Rich Phenols. Organic Letters, 20(8), 2190-2194. doi:10.1021/acs.orglett.8b00503

Yang, Z.-T., Yang, W.-L., Chen, L., Sun, H., & Deng, W.-P. (2018). Organocatalytic Enantioselective aza-Friedel-Crafts Reactions of Pyrazolinone Ketimines with Hydroxyindoles and Electron-Rich Phenols. Advanced Synthesis & Catalysis, 360(10), 2049-2054. doi:10.1002/adsc.201800181

Monti, S. A., Johnson, W. O., & White, D. H. (1966). The mannich reaction of hydroxyindoles. Tetrahedron Letters, 7(37), 4459-4464. doi:10.1016/s0040-4039(00)70059-1

Troxler, F., Bormann, G., & Seemann, F. (1968). Synthesen von Mannich-Basen von Hydroxy-indolen. 3. Mitteilung über synthetische Indol-Verbindungen [1]. Helvetica Chimica Acta, 51(6), 1203-1213. doi:10.1002/hlca.19680510603

Williams, S. J. (2012). Sulfatase inhibitors: a patent review. Expert Opinion on Therapeutic Patents, 23(1), 79-98. doi:10.1517/13543776.2013.736965

Woo, L. W. L., Purohit, A., & Potter, B. V. L. (2011). Development of steroid sulfatase inhibitors. Molecular and Cellular Endocrinology, 340(2), 175-185. doi:10.1016/j.mce.2010.12.035

Winum, J.-Y., Scozzafava, A., Montero, J.-L., & Supuran, C. T. (2004). Sulfamates and their therapeutic potential. Medicinal Research Reviews, 25(2), 186-228. doi:10.1002/med.20021

Kim, S. J., Jung, M.-H., Yoo, K. H., Cho, J.-H., & Oh, C.-H. (2008). Synthesis and antibacterial activities of novel oxazolidinones having cyclic sulfonamide moieties. Bioorganic & Medicinal Chemistry Letters, 18(21), 5815-5818. doi:10.1016/j.bmcl.2008.09.034

Kim, S. J., Park, H. B., Lee, J. S., Jo, N. H., Yoo, K. H., Baek, D., … Oh, C.-H. (2007). Novel lβ-methylcarbapenems having cyclic sulfonamide moieties: Synthesis and evaluation of in vitro antibacterial activity. European Journal of Medicinal Chemistry, 42(9), 1176-1183. doi:10.1016/j.ejmech.2007.02.001

Hanson, S. R., Whalen, L. J., & Wong, C.-H. (2006). Synthesis and evaluation of general mechanism-based inhibitors of sulfatases based on (difluoro)methyl phenyl sulfate and cyclic phenyl sulfamate motifs. Bioorganic & Medicinal Chemistry, 14(24), 8386-8395. doi:10.1016/j.bmc.2006.09.002

L. De Munck , C.Vila and J. R.Pedro , in Targets in Heterocyclic Chemistry , ed. O. A. Attanasi , P. Merino and D. Spinelli , Società Chimica Italiana , 2017 , p. 137

Lee, S. G., & Kim, S.-G. (2017). An asymmetric Brønsted acid-catalyzed Friedel–Crafts reaction of indoles with cyclic N-sulfimines. RSC Advances, 7(54), 34283-34286. doi:10.1039/c7ra06244c

Montesinos-Magraner, M., Cantón, R., Vila, C., Blay, G., Fernández, I., Muñoz, M. C., & Pedro, J. R. (2015). Organocatalytic enantioselective aza-Friedel–Crafts reaction of 2-naphthols with benzoxathiazine 2,2-dioxides. RSC Advances, 5(74), 60101-60105. doi:10.1039/c5ra11168d

Yan, Z., Gao, X., & Zhou, Y.-G. (2017). Enantioselective synthesis of quaternary α-aminophosphonates by organocatalytic Friedel–Crafts reactions of indoles with cyclic α-ketiminophosphonates. Chinese Journal of Catalysis, 38(5), 784-791. doi:10.1016/s1872-2067(17)62804-3

Rueping, M., Raja, S., & Núñez, A. (2011). Asymmetric Brønsted Acid-Catalyzed Friedel-Crafts Reactions of Indoles with Cyclic Imines - Efficient Generation of Nitrogen-Substituted Quaternary Carbon Centers. Advanced Synthesis & Catalysis, 353(4), 563-568. doi:10.1002/adsc.201000952

Zhou, D., Huang, Z., Yu, X., Wang, Y., Li, J., Wang, W., & Xie, H. (2015). A Quinine-Squaramide Catalyzed Enantioselective Aza-Friedel–Crafts Reaction of Cyclic Trifluoromethyl Ketimines with Naphthols and Electron-Rich Phenols. Organic Letters, 17(22), 5554-5557. doi:10.1021/acs.orglett.5b02668

Wu, L., Liu, R.-R., Zhang, G., Wang, D.-J., Wu, H., Gao, J., & Jia, Y.-X. (2015). Enantioselective Construction of Cyclic Indolyl α-Amino Estersviaa Friedel-Crafts Alkylation Reaction. Advanced Synthesis & Catalysis, 357(4), 709-713. doi:10.1002/adsc.201400987

Zhang, K.-F., Nie, J., Guo, R., Zheng, Y., & Ma, J.-A. (2013). Chiral Phosphoric Acid-Catalyzed Asymmetric Aza-Friedel-Crafts Reaction of Indoles with CyclicN-Acylketimines: Enantioselective Synthesis of Trifluoromethyldihydroquinazolines. Advanced Synthesis & Catalysis, 355(17), 3497-3502. doi:10.1002/adsc.201300534

Kano, T., Takechi, R., Kobayashi, R., & Maruoka, K. (2014). Chiral Brønsted acid-catalyzed enantioselective addition of indoles to ketimines. Org. Biomol. Chem., 12(5), 724-727. doi:10.1039/c3ob42190b

Xie, E., Rahman, A., & Lin, X. (2017). Asymmetric synthesis of CF3- and indole-containing tetrahydro-β-carbolines via chiral spirocyclic phosphoric acid-catalyzed aza-Friedel–Crafts reaction. Organic Chemistry Frontiers, 4(7), 1407-1410. doi:10.1039/c7qo00229g

We only observed the product alkylated at the C-4 position and we did not observe in the crude 1 H NMR any other alkylated product

Cyclic ketimines such as 4-methylbenzo[ e ][1,2,3]oxathiazine 2,2-dioxide or 3-methylbenzo[ d ]isothiazole 1,1-dioxide were not reactive under the optimized reaction conditions

CCDC 1875758 ( 3e ) and CCDC 1846586 ( 7a ) contains the supplementary crystallographic data for this paper

De Munck, L., Monleón, A., Vila, C., & Pedro, J. R. (2017). Diarylprolinol as a Ligand for Enantioselective Alkynylation of Cyclic Imines. Advanced Synthesis & Catalysis, 359(9), 1582-1587. doi:10.1002/adsc.201601379




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