NaHSO4-SiO2: An Efficient Reusable Green Catalyst for Selective C-3 Propargylation of Indoles with Tertiary Propargylic Alcohols

Document Type: Research Article


Department of Chemistry, University of the Free State, P.O. Box 339, Bloemfontein 9300, SOUTH AFRICA


Although several methods for the preparation of 4o propargyl indole derivatives have been published, this synthetic transformation is complicated by the tendency of 3o propargyl alcohols to form allenium intermediates in acidic media.  It is therefore a challenge to find an efficient method for the C-3 propargylation of indoles with 3° propargylic alcohols.  In this paper we wish to report on the successful application of silica gel impregnated with NaHSO4 as catalyst for the preparation of 4o propargyl indole derivatives.


Main Subjects

[1] Bandini M., Eichhozer, A., Catalytic Functionalization of Indoles in a New Dimension, Angew. Chem. Int. Ed., 48(51): 9608-9644 (2009).
[2] Sanz R., Miguel D., Gohain M., Garcia-Garcia. P., Fernández-Rodríguez M.A., González-Pérez A., Nieto-Faza O., de Lera A.R., Rodríguez F., Synthesis of Diverse Indole-Containing Scaffolds by Gold(I)-Catalyzed Tandem Reactions of 3-Propargylindoles Initiated by 1,2-Indole Migrations: Scope and Computational Studies, Chem. Eur. J., 16(32): 9818-9828 (2010).
[3] Müller T.J.J., Stereoselective Propargylations with Transition-Metal-Stabilized Propargyl Cations, Eur. J. Org. Chem., 2001(11): 2021-2033 (2001).
[4] Emer E., Sinisi R., Capdevila M.G., Petruzziello D., De Vincentiis F., Cozzi P.G.,  Direct Nucleophilic SN1-Type Reactions of Alcohols, Eur. J. Org. Chem., 2011(4): 647-666 (2011).
[5] Georgy M., Boucard V., Debleds O., Dal Zotto C., Campagne J. -M., Gold(III)-Catalyzed Direct Nucleophilic Substitution of Propargylic Alcohold, Tetrahedron, 65(9): 1758-1766 (2009).
[6] Kanao K., Matsuzawa H., Miyake Y., Nishibayashi Y., Ruthenium-Catalyzed Enantionselective Propargylation of Indoles with Propargylic Alcohold, Synthesis, 2008(23): 3869-3873 (2008).
[7] Whitney S., Grigg R., Derrick A., Keep A., Org. Lett., [Cp*IrCl2]2-Catalyzed Indirect Functionalization of Alcohols: Novel Strategies for the Synthesis of Substituted Indoles, Org. Lett., 9(17): 3299-3302 (2007).
[8] Matsuzawa H., Kanao K., Miyake Y., Nishibayashi Y., Remarkable Effect of N-Substituent on Enantioselective Ruthenium-Catalyzed Propargylation of Indoles with Propargylic Alcohols, Org. Lett., 9(26): 5561-5564 (2007).
[9] Inada Y., Yoshikawa M.,Milton M.D., Nishibayashi Y., Uemura S.,Ruthenium-Catalyzed Propargylation of Aromatic Compounds with Propargylic Alcohols, Eur. J.Org. Chem., 2006(4): 881-890(2006).
[10] Kennedy-Smith J.J., Young L.A., Toste F.D., Rhenium-Catalyzed Aromatic Propargylation, Org. Lett., 6(8):1325-1327(2004).
[11] Yadav J.S., Subba Reddy B.V., Raghavendra Rao K.V., Narayana Kumar G.G.K.S.,Sc(OTf)3-Catalyzed Alkylation of Indoles with Propargyl Alcohols: an Expeditious Synthesis of 3-Substituted Indoles, Tetrahedron Lett., 48(31):5573-5576 (2007).
[12] Jana U., Maiti S., Biswas S., An FeCl3-Catalyzed Highly C3-Selective Friedel-Crafts Alkylation of Indoles with Alcohols, Tetrahedron Lett., 48(40): 7160-7163 (2007).
[13] Yadav J.S., Subba Reddy B.V., Raghavendra Rao K.V., Narayana Kunar G.G.K.S., Indium(III) Bromide Catalyzed Rapid Propargylation of Heteroaromatic Systems by α-Aryl-Substituted Propargyl Alcohols, Synthesis, 2007(20): 3205-3210(2007).
[14] Srihari P., Bhunia D.C., Sreedhar P., Mandal S.S., Shyam Sunder Reddy J., Yadav J.S., Iodine-Catalyzed C-and O-Nucleophilic Substitution Reactions of Aryl-Propargyl Methanols, Tetrahedron Lett., 48(46):8120-8124(2007).
[15] Gohain M., Marais C., Bezuidenhoudt B.C.B., An Al(OTf)3-Catalyzed Environmentally Benign Process for the Propargylation of Indoles, Tetrahedron Lett., 53(35): 4704-4707 (2012).
[16] Sanz R., Gohain M., Miguel D., Martínez A., Rodríguez F., Synthesis of 3-Allenylindoles and 3-Dienylindoles by Brønsted Acid Catalyzed Allenylation of 2-Arylindoles with Tertiary Propargylic Alcohols, Synlett, 2009(12): 1985-1989(2009).
[17] Sanz R., Miguel D., Álvarez-Gutiérrez J.M., Rodríguez F., Brønsted Acid Catalyzed C3-Selective Propargylation and Benzylation of Indoles with Tertiary Alcohols, Synlett, 2008(7):975-978 (2008).
[18] Shirakawa S., Kobayashi S., Surfactant-Type Brønsted Acid Catalyzed Dehydrative Nucleophilic Substitutions of Alcohols in Water, Org. Lett., 9(2): 311-314 (2007).
[19] Motokura K., Nakagiri N., Mizugaki T., Ebitani K., Kaneda K., Nucleophilic Substitution Reactions of Alcohols with Use of Montmorillonite Catalysts as Solid Brønsted Acids, J. Org. Chem.,72(16):6006-6015(2007).
[20] Le Bras J., Muzart J., Brønsted-Acid-Catalyzed Coupling of Electron-Rich Arenes with Substituted Allylic and Secondary Benzylic Alcohols, Tetrahedron, 63(33):7942-7948(2007).
[21] Olah G.A., Laali K.K., Wang Q., Prakash G.K.S., "Onium Ions"; John Wiley & Sons, Inc., New York, (1998).
[22] Ohta A., Dahl K., Raab R., Geittner J., Huisgen R., Diazodiphenylmethane and Monosubstituted Butadienes: Kinetics and a New Chapter of Vinylcyclopropane Chemistry, Helv. Chim. Acta, 91(5):783-804 (2008).
[23] Sartori G., Maggi R., Chem.Rev., 111: PR181-PR214 (2011).
[24] Fricke R., Kosslick H., Lischke G., Richter M., Incorporation of Gallium into Zeolites: Syntheses, Properties and Catalytic Application, Chem. Rev., 100(6): 2303-2406 (2003).
[25] Chakroborti A.K., Gulhane R., Perchloric Acid Adsorbed on Silica Gel as A New, Highly Efficient, and Versatile Catalyst for Acetylation of Phenols, Thiols, Alcohols, and Amines, Chem. Commun., 2003(15): 1896-1897 (2003).
[26] Wilson K., Clark J.H., Solid Acids and Their Use as Environmentally Friendly Catalysts in Organic Synthesis, Pure Appl. Chem., 72(7): 1313-1319 (2000).
[27] Wu L., Yang C., Zhang C., Yang L., HClO4-SiO2 and NaHSO4-SiO2: Two Efficient Heterogeneous Catalysts for Synthesis of N-Acylsulfonamides under Solvent-Free Conditions, Lett. Org. Chem., 6(3): 234-236 (2009).
[28] Rostamizadeh S., Shadjou N., Amani A.M., Balalaie S., Silica Supported Sodium Hydrogen Sulfate (NaHSO4/SiO2): A Mild and Efficient Reusable Catalyst for the Synthesis of Aryl-14-H-dibenzo [a,j]xanthenes under Solvent-free Conditions, Chinese Chem. Lett., 19(10): 1151-1155 (2008).
[29] Kolvari E., Sodium Hydrogen Sulfate: Safe and Efficient, Synlett, 2006(12): 1971-1972 (2006).
[30] BretonG.W., Selective Monoacetylation of Unsymmetrical Diols Catalyzed by Silica Gel- Supported Sodium Hydrogen Sulfate, J. Org. Chem., 62(25):8952-8954(1997).
[31] Ramesh C., Banerjee J., Pal R., Das B., Silica Supported Sodium Hydrogen Sulfate and Amberlyst-15: Two Efficient Heterogeneous Catalysts for Facile Synthesis of Bis-and Tris(1H-indol-3-yl)methanes from Indoles and Carbonyl Compounds, Adv. Synth. Catal., 354(5):557-559 (2003).
[32] Ramesh C., Mahender G., Ravindranath N., Das B., A Simple, Mild and Efficient Procedure for Selective Cleavage of Prenyl Esters Using Silica-Supported Sodium Hydrogen Sulphate as A Heterogenous Catalyst, Tetrahedron Lett., 44(7):1465-1467(2003).
[33] Karimi A.R., Alimohammadi Z., Azizian A., Mohammadi A.A., Mohammadizadeh M.R., Solvent-Free Synthesis of Tetrasubstituted Imidazoles on Silica Gel/NaHSO4 Support, Catal. Commun., 7(9): 728-732 (2006).
[34] Bazgir A., Microwave-Assisted Efficient Synthesis of Diimines in Dry Media Using Silica Gel Supported Sodium Hydrogen Sulfate as Reusable Solid Support, J. Chem. Res., 2006(1): 1-2 (2006).
[35] Das B., Laxminarayana K., Krishnaish M., Srinivas Y., An Efficient and Convenient Protocol for the Synthesis of Novel 12-Aryl-or 12-Alkyl-8,9,10,12- tetrahydrobenzo-[a]xanthen -11-one Derivatives, Synlett, 2007(20): 3107-3112 (2007).
[36] Gopalkrishnan M., Sureshkumar P., Thanusu J., Kanagarajan V., Three Components Coupling Catalysed by NaHSO4.SiO2–A Convenient Synthesis, Antibacterial and Antifungal Activities of Novel 6-Aryl-1,2,4,5-tetrazinan-3-ones, J. Enzym. Inhib. Med. Chem., 23(1): 87-93 (2008).
[37] Das B., Veeranjaneyulu B., Krishnaiah M., Balasubramanyam P., Synthesis of Gem-Dihydroperoxides from Ketones Using Silica-Supported Sodium Hydrogen Sulfate as a Heterogeneous Catalyst, J. Mol. Catal. A-Chem., 284(1-2): 116-119 (2008).
[38] Sapkal S.B., Shelke K.F., Shingate B.B., Shingare M.S., NaHSO4/SiO2: An Efficient Catalyst for the Synthesis of b-Enaminones and 2-Methylquinolin-4(1H)-ones under Solvent-Free Conditions, J. Korean Chem. Soc., 54(6): 723-726 (2010).
[39] Gohain M., Marais C., Bezuidenhoudt B.C.B., Al(OTf)3: An Efficient Recyclable Catalyst for Direct Nucleophilic Substitution of the Hydroxy Group of Propargylic Alcohols with Carbon-and Heteroatom-Centered Nucleophiles to Construct C–C, C–O, C–N and C–S Bonds, Tetrahedron Lett., 53(9): 1048-1050 (2012).
[40] Sanz R., Miguel D., Martinez A., Gohain M., García-García P., Fernández-Rodríguez M.A., Álvarez E., Rodríguez F., Brønsted Acid Catalyzed Alkylation of Indoles with Tertiary Propargylic Alcohols: Scope and Limitations, Eur. J. Org. Chem., 2010(36): 7027-7039 (2010).
[41] Rao W., Zhang X., Sze E.M.L., Chan P.W.H., Ytterbium(III) Triflate-Catalyzed Amination of
1-Cyclopropylprop-2-yn-1-ols as an Expedient Route to Conjugated Enynes, J. Org. Chem., 74(4): 1740-1743 (2009).
[42] Azarifar D., Forghaniha A., A Novel Chemoselective Reaction of Aldehydes with 2-Mercaptoethanol Catalyzed by SiO2-NaHSO4 under Solvent-free Condition, J. Chin. Chem. Soc., 53(5), 1189-1192 (2006).