Despite hydroformylation being a very efficient method for the transformation of alkenes, it is not commonly employed in laboratories owing to the flammable/toxic nature of hydrogen and carbon monoxide gases and the necessity of high-pressure equipment in a batch system. Flow chemistry often raises the safety profiles against high-pressure and toxic gases because the diameter of the flow reactor is small. Herein, we show that aliphatic alkenes can be safely hydroformylated in a flow reactor. In our flow method, although the target hydroformylated product was obtained in a low yield (19%), toxic gases were safely treated using a flow reactor. Better yields could possibly be achieved by recycling of the unreacted alkene.
Speight, J.G. (2014) The Chemistry and Technology of Petroleum. 5th Edition, CRC Press, Taylor & Francis Group, Boca Raton, FL.
Adkins, H. and Krsek, G. (1949) Hydroformylation of Unsaturated Compounds with a Cobalt Carbonyl Catalyst. Journal of the American Chemical Society, 71, 3051-3055. https://doi.org/10.1021/ja01177a032
Evans, D., Osborn, J.A. and Wilkinson, G. (1968) Hydroformylation of Alkenes by Use of Rhodium Complex Catalysts. Journal of the Chemical Society A, 33, 3133-3142. https://doi.org/10.1039/j19680003133
Breit, B. (2003) Synthetic Aspects of Stereoselective Hydroformylation. Accounts of Chemical Research, 36, 264-275. https://doi.org/10.1021/ar0200596
Franke, R., Selent, D. and Borner, A. (2012) Applied Hydroformylation. Chemical Reviews, 112, 5675-5732. https://doi.org/10.1021/cr3001803
Smidt, J., Hafner, W., Jira, R., Sieber, R., Sedlmeier, J. and Sabel, A. (1962) The Oxidation of Olefins with Palladium Chloride Catalysts. Angewandte Chemie International Edition, 1, 80-88. https://doi.org/10.1002/anie.196200801
Tsuji, J. (1984) Synthetic Applications of the Palladium-Catalyzed Oxidation of Olefins to Ketones. Synthesis, 1984, 369-384. https://doi.org/10.1055/s-1984-30848
Weissermel, K. and Arpe, H.-J. (1988) Industrielle Organische Chemie. VCH Publishers, Weinheim.
Takahashi, T., Machida, K., Kido, Y., Nagashima, K., Ebata, S. and Doi, T. (1997) Hydroformylation of ω-Functionalized 1,1-Disubstituted Alkenes and Its Use Toward the Synthesis of (±)Muscone. Chemistry Letters, 26, 1291-1292. https://doi.org/10.1246/cl.1997.1291
Eilbracht, P., Barfacker, L., Buss, C., Hollmann, C., Kitsos-Rzychon, B.E., Kranemann, C.L., Rische, T., Roggenbuck, R. and Schmidt, A. (1999) Tandem Reaction Sequences under Hydroformylation Conditions: New Synthetic Applications of Transition Metal Catalysis. Chemical Reviews, 99, 3329-3365. https://doi.org/10.1021/cr970413r
Liu, P. and Jacobsen, E.N. (2001) Total Synthesis of (+)-Ambruticin. Journal of the American Chemical Society, 123, 10772-10773. https://doi.org/10.1021/ja016893s
Airiau, E., Spangenberg, T., Girard, N., Breit, B. and Mann, A. (2010) Short Access to (+)-Lupinine and (+)-Epiquinamide via Double Hydroformylation. Organic Letters, 12, 528-531. https://doi.org/10.1021/ol902718q
McDonald, R.I., Wong, G.W., Neupane, R.P., Stahl, S.S. and Landis, C.R. (2010) Enantioselective Hydroformylation of N-Vinyl Carboxamides, Allyl Carbamates, and Allyl Ethers Using Chiral Diazaphospholane Ligands. Journal of the American Chemical Society, 132, 14027-14029. https://doi.org/10.1021/ja106674n
Chiou, W.-H., Mizutani, N. and Ojima, I. (2007) Highly Efficient Synthesis of Azabicyclo[x.y.0]alkane Amino Acids and Congeners by Means of Rh-Catalyzed Cyclohydrocarbonylation. Journal of Organic Chemistry, 72, 1871-1882. https://doi.org/10.1021/jo061692y
Campi, E.M., Jackson, W.R. and Nilsson, Y. (1991) A Hydroformylation Route to β-Substituted Pyrroles. Tetrahedron Letters, 32, 1093-1094. https://doi.org/10.1016/S0040-4039(00)74496-0
Wuts, P.G.M., Obrzut, M.L. and Thompson, P.A. (1984) Hydroformylation as a Simple and Efficient One Carbon Homologation of Homoallylic Alcohols. Synthesis of Prelog-Djerassi Lactone. Tetrahedron Letters, 25, 4051-4054. https://doi.org/10.1016/S0040-4039(01)90179-0
Yoshida, J., Takahashi, Y. and Nagaki, A. (2013) Flash Chemistry: Flow Chemistry That Cannot Be Done in Batch. Chemical Communications, 49, 9896-9904. https://doi.org/10.1039/C3CC44709J
Movsisyan, M., Delbeke, E.I.P., Berton, J.K.E.T., Battilocchio, C., Ley, S.V. and Stevens, C.V. (2016) Taming Hazardous Chemistry by Continuous Flow Technology. Chemical Society Reviews, 45, 4892-4928. https://doi.org/10.1039/C5CS00902B
Fuse, S., Mifune, Y. and Takahashi, T. (2014) Efficient Amide Bond Formation through a Rapid and Strong Activation of Carboxylic Acids in a Microflow Reactor. Angewandte Chemie International Edition, 53, 851-855. https://doi.org/10.1002/anie.201307987
Fuse, S., Tanabe, N., Yoshida, M., Yoshida, H., Doi, T. and Takahashi, T. (2010) Continuous-Flow Synthesis of Vitamin D3. Chemical Communications, 46, 8722-8724. https://doi.org/10.1039/c0cc02239j
Mallia, C.J. and Baxendale, I.R. (2016) The Use of Gases in Flow Synthesis. Organic Process Research & Development, 20, 327-360. https://doi.org/10.1021/acs.oprd.5b00222
Wegner, J., Ceylan, S. and Kirschning, A. (2011) Ten Key Issues in Modern Flow Chemistry. Chemical Communications, 47, 4583-4592. https://doi.org/10.1039/c0cc05060a
Kasinathan, S., Bourne, S., Tolstoy, P., Koos, P., O’Brien, M., Bates, R.W., Baxendale, I.R. and Ley, S.V. (2011) Syngas-Mediated C–C Bond Formation in Flow: Selective Rhodium-Catalysed Hydroformylation of Styrenes. Synlett, 2011, 2648-2651. https://doi.org/10.1055/s-0031-1289292
Koos, P., Gross, U., Polyzos, A., O’Brien, M., Baxendale, I.R. and Ley, S.V. (2011) Teflon AF-2400 Mediated Gas-Liquid Contact in Continuous Flow Methoxycarbonylations and In-Line FTIR Measurement of CO Concentration. Organic & Biomolecular Chemistry, 9, 6903-6908. https://doi.org/10.1039/c1ob06017a
Polyzos, A., O’Brien, M., Peterson, T.P., Baxendale, I.R. and Ley, S.V. (2011) The Continuous-Flow Synthesis of Carboxylic Acids Using CO2 in a Tube-In-Tube Gas Permeable Membrane Reactor. Angewandte Chemie International Edition, 50, 1190-1193. https://doi.org/10.1002/anie.201006618
O’Brien, M., Baxendale, I.R. and Ley, S.V. (2010) Flow Ozonolysis Using a Semipermeable Teflon AF-2400 Membrane To Effect Gas-Liquid Contact. Organic Letters, 12, 1596-1598. https://doi.org/10.1021/ol100322t
O’Brien, M., Taylor, M., Polyzos, A., Baxendale, I.R. and Ley, S.V. (2011) Hydrogenation in Flow: Homogeneous and Heterogeneous Catalysis Using Teflon AF-2400 to Effect Gas-Liquid Contact at Elevated Pressure. Chemical Science, 2, 1250-1257. https://doi.org/10.1039/c1sc00055a
Kranenburg, M., van der Burgt, Y.E.M., Kamer, P.C.J., van Leeuwen, P.W.N.M., Goubitz, K. and Fraanje, J. (1995) New Diphosphine Ligands Based on Heterocyclic Aromatics Inducing Very High Regioselectivity in Rhodium-Catalyzed Hydroformylation. Organometallics, 14, 3081-3089. https://doi.org/10.1021/om00006a057