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Diels-Alder reactions in aqueous media

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Abstract

Prior to Breslow’s pioneering work in the early 1980s, the use of water as a solvent for the Diels-Alder reaction was a fairly rare occurrence. It is perhaps fitting that the earliest known example of such a reaction was actually reported by Diels and Alder themselves in 1931 [1].

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References

  1. Diels, O.; Alder, K., Synthesen in der hydroaromatische Reihe, Ann. Chem., 1931, 490, 243–257.

    Google Scholar 

  2. Woodward, R.B.; Baer, H., The reaction of furan with maleic anhydride, J. Am. Chem. Soc., 1948, 70, 1161.

    Article  CAS  Google Scholar 

  3. Hopff, H.; Rautenstrauch, C.W., Production of addition products from dienes and compounds having an unsaturated carbon linkage activated by substituents, US Patent 2262002, 1939; Chem. Abstr., 1942, 36, 10469.

    Google Scholar 

  4. Lane, L.C.; Parker, C.H., Jr., Fumaric acid-conjugated hydrocarbon adducts, US Patent 2444263, 1948; Chem. Abstr., 1948, 42, 7102.

    Google Scholar 

  5. Bandaranayake, W.M.; Banfield, J.E.; Black, D.S.C., Postulated electrocyclic reactions leading to endriandric acid and related natural products, J. Chem. Soc., Chem. Commun., 1980, 902–903.

    Google Scholar 

  6. Breslow, R.; Rideout, D.C., Hydrophobic acceleration of Diels-Alder reactions, J. Am. Chem. Soc., 1980, 102, 7816–7817.

    Article  Google Scholar 

  7. Schneider, H.-J.; Sangwan, N.K., Diels-Alder reactions in hydrophobic cavities: a quantitative correlation with solvophobicity and rate enhancements by macrocycles, J. Chem. Soc., Chem. Commun., 1986, 1787–1789.

    Google Scholar 

  8. Sangwan, N.K.; Schneider, H.-J., The kinetic effects of water and of cyclodextrins on Diels-Alder reactions. Host-guest chemistry. Part 18, J. Chem. Soc., Perkin Trans. 2, 1989, 1223–1227.

    Google Scholar 

  9. Breslow, R.; Rizzo, C.L., Chaotropic salt effects in a hydrophobically accelerated Diels-Alder reaction, J. Am. Chem. Soc., 1991, 113, 4340–4341.

    Article  CAS  Google Scholar 

  10. Breslow, R., Hydrophobic effects on simple organic reactions in water, Acc. Chem. Res., 1991, 24, 159–164.

    Article  CAS  Google Scholar 

  11. Breslow, R., Hydrophobic and antihydrophobic effects on organic reactions in aqueous solution, in Structure and Reactivity in Aqueous Solution, Cramer, C.J.; Truhlar, D.G., Eds.; ACS Symposium Series 568; American Chemical Society, Washington, DC, 1994, pp. 291–302.

    Chapter  Google Scholar 

  12. Blokzijl, W.; Blandamer, M.J.; Engberts, J.B.F.N., Diels-Alder reactions in aqueous solutions. Enforced hydrophobic interactions between diene and dienophile, J. Am. Chem. Soc., 1991, 113, 4241–4246.

    Article  CAS  Google Scholar 

  13. Blokzijl, W.; Engberts, J.B.F.N., Initial-state and transition-state effects on Diels-Alder reactions in water and mixed aqueous solvents, J. Am. Chem. Soc., 1992, 114, 5440–5442.

    Article  CAS  Google Scholar 

  14. Blokzijl, W.; Engberts, J.B.F.N., Enforced hydrophobic interactions and hydrogen bonding in the acceleration of Diels-Alder reactions in water, in Structure and Reactivity in Aqueous Solution, Cramer, C.J.; Truhlar, D.G., Eds.; ACS Symposium Series 568; American Chemical Society, Washington, DC, 1994, pp. 303–317.

    Chapter  Google Scholar 

  15. Breslow, R.; Zhu, Z., Quantitative antihydrophobic effects as probes for transition rate structures. 2. Diels-Alder reactions, J. Am. Chem. Soc., 1995, 117, 9923–9924.

    Article  CAS  Google Scholar 

  16. Lubineau, A.; Bienaymé, H.; Queneau, Y.; Scherrmann, M.-C., Aqueous cycloadditions using glyco-organic substrates. Thermodynamics of the reaction, New J. Chem., 1994, 18, 279–285.

    CAS  Google Scholar 

  17. Blake, J.F.; Lim, D.; Jorgensen, W.L. Enhanced hydrogen bonding of water to Diels-Alder transition states. Ab initio evidence, J. Org. Chem., 1994, 59, 803–805.

    Article  CAS  Google Scholar 

  18. Jorgensen, W.L.; Blake, J.F.; Lim, D.; Severence, D.L., Investigation of solvophobic effects on pericyclic reactions by computer simulations, J. Chem. Soc., Faraday Trans., 1994, 90, 1727–1732.

    Article  CAS  Google Scholar 

  19. Otto, S.; Blokzijl, W.; Engberts, J.B.F.N., Diels-Alder reactions in water. Effects of hydrophobicity and hydrogen bonding, J. Org. Chem., 1994, 59, 5372–5376.

    Article  CAS  Google Scholar 

  20. Grieco, P.A.; Garner P.; He, Z.-M., ‘Micellar’ catalysis in the aqueous intermolecular Diels-Alder reaction: rate acceleration and enhanced selectivity, Tetrahedron Lett., 1983, 24, 1897–1900.

    Article  CAS  Google Scholar 

  21. Grieco, P.A.; Yoshida, K.; Garner P., Aqueous intermolecular Diels-Alder chemistry: reactions of diene carboxylates with dienophiles in water at ambient temperature, J. Org. Chem., 1983, 26, 3137–3139.

    Article  Google Scholar 

  22. Yoshida, K.; Grieco, P.A., Synthesis and reactivity of (E)-4,6,7—octatrienoic acid sodium salt in the aqueous Diels-Alder reaction, Chem. Lett., 1985, 155–158.

    Google Scholar 

  23. Grieco, P.A.; Galatsis, P.; Spohn, R.F., Aqueous intermolecular Diels-Alder chemistry. Reaction of (E)-2,4-pentadienyl ammonium chloride and related ammonium salts with dienophiles in water, Tetrahedron, 1986, 42, 2847–2853.

    Article  CAS  Google Scholar 

  24. Unpublished results of Mr. Zen-Min He, Indiana University.

    Google Scholar 

  25. Keana, J.F.W.; Guzikowski, A.P.; Morat, C.; Volwerk, J.J., Detergents containing a 1,3-diene group in the hydrophobic segment. Facile chemical modification by a Diels-Alder reaction with hydrophobic dienophiles in aqueous solution, J. Org. Chem., 1983, 48, 2661–2666.

    Article  CAS  Google Scholar 

  26. See references [7] and [8].

    Google Scholar 

  27. Braun, R.; Schuster, F.; Sauer, J., (4+2)-Cycloadditionen in Micellen: Ein Vergleich des Produktspectrums und der Reaktionsgeschwindigkeit mit Reaktionen in Lösung, Tetrahedron Lett., 1986, 27, 1285–1288.

    Article  CAS  Google Scholar 

  28. Singh, V.; Raju, B.N.S, p4S + p2S cycloaddition of spiro[4,n] cyclic 1,3-dienes with quinones in homogeneous and aqueous micellar media: synthesis of novel polycyclic cage diones, Ind. J. Chem., 1996, 35B, 303–311.

    CAS  Google Scholar 

  29. Otto, S.; Engberts, J.B.F.N., Lewis-acid catalysis of a Diels-Alder reaction in water, Tetrahedron Lett., 1995, 36, 2645–2648

    Article  CAS  Google Scholar 

  30. Kobayashi, S.; Hachiya, I.; Araki, M.; Ishitani, H., Scandium trifluoromethanesulfonate (Sc(OTf)3). A novel reusable catalyst in the Diels-Alder reaction, Tetrahedron Lett., 1993, 34, 3755–3758.

    Article  CAS  Google Scholar 

  31. Breslow, R.; Guo, T., Diels-Alder reactions in nonaqueous polar solvents. Kinetic effects of chaotropic and antichaotropic agents and of β-cyclodextrin, J. Am. Chem. Soc., 1988, 110, 5613–5617.

    Article  CAS  Google Scholar 

  32. Dunams, T.; Hoekstra, W.; Pentaleri, M.; Liotta, D, Molecular aggregation and its applicability to synthesis. The Diels-Alder reaction, Tetrahedron Lett., 1988, 29, 3745–3748.

    Article  CAS  Google Scholar 

  33. Jaeger, D.A.; Tucker, C.E., Diels-Alder reactions in ethylammonium nitrate, a low-melting fused salt, Tetrahedron Lett., 1989, 30, 1785–1788.

    Article  CAS  Google Scholar 

  34. Pai, C.K.; Smith, M.B., Rate enhancement in dilute salt solutions of aqueous ethanol: the Diels-Alder reaction, J. Org. Chem., 1995, 60, 3731–3735.

    Article  CAS  Google Scholar 

  35. Casetta, M.; Colona, S.; Manfredi, A., Hydrophobic control of organic stereochemistry. Changes of regioselectivity in Diels-Alder reactions by salt effects, Gazz. Chim. Ital., 1989, 119, 533–535.

    CAS  Google Scholar 

  36. Kelley, T.R.; Montury, M., Lewis acid-catalyzed Diels-Alder reactions of perihydroxylated naphthoquinones: a regiochemical divergence, Tetrahedron Lett., 1978, 4311–4314.

    Google Scholar 

  37. Chung, W.-S.; Wang, J.-Y., Control of regioselectivity in the Diels-Alder reactions of alkylsubstituted 1,4-benzoquinones by β-cyclodextrin and its derivatives, J. Chem. Soc., Chem. Commun., 1995, 971–972.

    Google Scholar 

  38. Jaeger, D.A.; Shinozaki, H.; Goodson, P.A., Diels-Alder reactions of a surfactant 1, 3-diene, J. Org. Chem., 1991, 56, 2482–2489.

    Article  CAS  Google Scholar 

  39. Breslow, R.; Maitra, U.; Rideout, D., Selective Diels-Alder reactions in aqueous solutions and suspensions, Tetrahedron Lett., 1983, 24, 1901–1904.

    Article  CAS  Google Scholar 

  40. Breslow, R.; Maitra, U., On the origin of product selectivity in aqueous Diels-Alder reactions, Tetrahedron Lett., 1984, 25, 1239–1240.

    Article  CAS  Google Scholar 

  41. Braun, R.; Schuster, F.; Sauer, J., (4+2)-cycloadditionen in Micellen: Ein Vergleich des Productspektrums und der Reaktiongeschwendigkeit mit Reaktionen in Lösung, Tetrahedron Lett., 1986, 27, 1285–1288.

    Article  CAS  Google Scholar 

  42. Schneider, H.-J.; Sangwan, N.K., Changes of stereoselectivity in Diels-Alder reactions by hydrophobic solvent effects and by β-cyclodextrin, Angew. Chem. Int. Ed. Engl., 1987, 26, 896–897.

    Article  Google Scholar 

  43. Cativiela, C.; Garcia, J.I.; Mayoral, J.A.; Avenoza, A.; Peregrina, J.M.; Roy, M.A., Development of a model to explain the influence of the solvent on the rate and selectivity of Diels-Alderreactions, J. Phys. Org. Chem., 1991, 4, 48–52.

    Article  CAS  Google Scholar 

  44. See reference [20].

    Google Scholar 

  45. Griesbeck, A.G., Fulvene cycloaddition reactions in water: influence on rate and selectivity, Tetrahedron Lett., 1988, 29, 3477–3480.

    Article  CAS  Google Scholar 

  46. Rao, K.R.; Srinivasan, T.N.; Bhanumathi, N., A stereoselective biocatalytic Diels-Alder reaction, Tetrahedron Lett., 1990, 31, 5959–5960.

    Article  CAS  Google Scholar 

  47. Paquette, L.A., Asymmetric cycloaddition reactions, in Asymmetric Synthesis, Morrison, J.D., Ed.; Academic Press, Orlando, 1984, vol. 3, Ch. 7.

    Google Scholar 

  48. Ghosh, A.K.; Mathivanan, P.; Cappiello, J., Conformationally contrained bis(oxazoline) derived chiral catalyst: A highly effective enantioselective Diels-Alder reaction, Tetrahedron Lett., 1996, 37, 3515–3518, and references therein.

    Article  Google Scholar 

  49. Dols, P.P.M.A.; Klunder, A.J.H.; Zwanenburg B., 4-Hydroxycyclopent-2-en-l-one and derivatives as chiral synthetic equivalents of cyclopentadienone in asymmetric Diels-Alder reactions, Tetrahedron, 1994, 28, 8515–8538.

    Article  Google Scholar 

  50. Cieplak, A.S., Stereochemistry of nucleophilic addition to cyclohexanone. The importance of two-electron stabilizing interactions, J. Am. Chem. Soc., 1981, 103, 4540–4552.

    Article  CAS  Google Scholar 

  51. Jeroncic, L.O.; Cabal, M.P.; Danishefsky, S.J.; Shulte, G.M., On the diastereofacial selectivity of Lewis acid catalyzed carbon-carbon bond forming reactions of conjugated cyclic enones bearing electron-withdrawing substituents at the γ-position, J. Org. Chem., 1991, 56, 387–395.

    Article  CAS  Google Scholar 

  52. Proust, S.M.; Ridley, D.D., Effect of catalyst and solvent on the stereochemistry of Diels-Alder reactions between cyclopentadiene and 3-phenylsulfinylprop-2-enoic acids and methyl esters, Aust. J. Chem., 1984, 37, 1677–1688.

    Article  CAS  Google Scholar 

  53. Waldmann, H.; Dräger, M., Thermische Diels-Alder-Reactionen mit N-(2-Alkenoyl)-(S)-prolinestern als chiralen Dienophilen in organischen und wässrigen Reaktionsmedien, Ann. Chem., 1990, 681–685.

    Google Scholar 

  54. Masamune, S.; Choy, W.; Petersen, J.S.; Sita, L.R., Double asymmetric synthesis and a new strategy for stereochemical control in organic synthesis, Angew. Chem. Int. Ed. Engl., 1985, 24, 1–30.

    Article  Google Scholar 

  55. Geary, P.J.; Pryce, R.L.; Roberts, S.M.; Ryback, G.; Winders, J.A., The oxidations of norbornadiene and some derivatives using Pseudomonas sp., J. Chem. Soc., Chem. Commun., 1990, 204–205.

    Google Scholar 

  56. Brandes, E.; Grieco, P.A.; Garner P., Diastereoselection in an aqueous Diels-Alder reaction: A formal total synthesis of the Inhoffen-Lythgoe diol, J. Chem. Soc., Chem. Commun., 1988, 500–502.

    Google Scholar 

  57. Lubineau, A.; Queneau, Y., Stereochemical variations in aqueous cycloadditions using glyco-organic substrates as a consequence of chemical manipulations on the sugar moiety, Tetrahedron, 1989, 45, 6697–6712, and references therein.

    Article  CAS  Google Scholar 

  58. Goeljian, P.G.; Wu, T.-C.; Kishi, Y., Preferred conformation of C-glycosides. 6. Conformational similarity of glycosides and corresponding C-glycosides, J. Org. Chem., 1991, 56, 6412–6422.

    Article  Google Scholar 

  59. Lubineau, A.; Augé, J.; Lubin, N., Aqueous cycloaddition using glyco-organic substrates. Facial selectivity in Diels-Alder reactions of a chiral diene derived from D-glyceraldehyde, J. Chem. Soc., Perkin Trans. 1, 1990, 3011–3015.

    Article  Google Scholar 

  60. Yoshida, K.; Grieco, P.A., Aqueous Diels-Alder chemistry: vernolepin revisited, J. Org. Chem., 1984, 49, 5257–5260.

    Article  CAS  Google Scholar 

  61. Kieczykowski, G.R.; Queseda, M.L.; Schiessinger, R.H., Total synthesis of dl-bisnorvernolepin, J. Am. Chem. Soc., 1980, 102, 782–790.

    Article  CAS  Google Scholar 

  62. Drewes, S.E.; Grieco, P.A.; Huffman, J.C., A short synthesis of dl-epi-pyroangolensolide and dl-pyroangolensolide: confirmation of the structures of pyroangolensolide and calodendrolide, J. Org. Chem., 1985, 50, 1309–1311.

    Article  CAS  Google Scholar 

  63. See reference [20].

    Google Scholar 

  64. Grieco, P.A.; Collins, J.L.; Moher, E.D.; Fleck, T.J.; Gross, R.S., Synthetic studies on quassinoids: total synthesis of (−)-chapparinone, (−)-glucarubolone, and (+)-glaucarubinone, J. Am. Chem. Soc., 1993, 115, 6078–6093, and references therein.

    Article  CAS  Google Scholar 

  65. See reference [57].

    Google Scholar 

  66. Trost, B.M.; Bernstein, P.R.; Funfschilling, P.C., A stereocontrolled approach toward vitamin D metabolites. A synthesis of the Inhoffen-Lythgoe diol, J. Am. Chem. Soc., 1979, 101, 4378–4380.

    Article  CAS  Google Scholar 

  67. Lythgoe, B.; Moran, T.A.; Nambudiry, M.E.N.; Tideswell, J.; Wright, P.W., J. Chem. Soc., Perkins Trans. 1, 1978, 590.

    Google Scholar 

  68. Brandes, E.; Grieco, P.A.; Gajewski, J.J., Effect of polar solvents on the rates of Claisen rearrangements: asessment of ionic character, J. Org. Chem., 1989, 54, 515–516.

    Article  CAS  Google Scholar 

  69. Baillie, L.C.; Bearder, J.R.; Whiting, D.A., Synthesis of the A/E/F tricyclic section of the norditerpenoid alkaloid methyllycaconitine, a potent inhibitor of neurotransmission, J. Chem. Soc., Chem. Commun., 1994, 2487–2488.

    Google Scholar 

  70. Saksena, A.K.; Girijavallabhan, V.M.; Chen, Y.-T.; Jao, E.; Pike, R.E.; Desai, J.A.; Rane, D.; Ganguly, A.K., Aqueous Diels-Alder reactions of electron deficient 2-arylfurans: a highly stereoselective route to 2,2,5-trisubstituted tetrahydrofurans towards a novel class of orally active azole antifungals, Heterocycles, 1993, 35, 129–134.

    Article  CAS  Google Scholar 

  71. See reference [14].

    Google Scholar 

  72. Keay, B.A., Intramolecular Diels-Alder reaction of the diene unit of furan in 2.0 M CaCl2, J. Chem. Soc., Chem. Commun., 1987, 419–421.

    Google Scholar 

  73. Sternbach, D.D.; Rossana, D.M., Cyclodextrin catalysis in the intramolecular Diels-Alder reaction with the furan diene, J. Am. Chem. Soc., 1982, 104, 5853–5854

    Article  CAS  Google Scholar 

  74. Wang, W.-B.; Roskamp, E.J., New technology for the construction of bicyclo[6.2.1] ring systems, Tetrahedron Lett., 1992, 33, 7631–7634

    Article  CAS  Google Scholar 

  75. Hudlicky, T.; Butora, G.; Fearnley, S.P.; Gum, A.G.; Persichini, P.J., III; Stabile, M.R.; Merola, J.S., Intramolecular Diels-Alder reactions of the furan diene (IMDAF); rapid construction of highly functionalised isoquinoline skeletons, J. Chem. Soc., Perkin Trans. 1, 1995, 2393–2398.

    Article  Google Scholar 

  76. Van Royen, L.A.; Mijngheer, R.; De Clercq, P.J., Intramolecular Diels-Alder reaction with furan-diene. Total synthesis of (±)-11-ketotestosterone and (±)-adrenosterone, Tetrahedron, 1985, 41, 4667–4680.

    Article  Google Scholar 

  77. Williams D.R.; Gaston, R.D.; Horton, I.B., III, Intramolecular Diels-Alder cycloadditions of bis-diene substrates, Tetrahedron Lett., 1985, 26, 1391–1394.

    Article  CAS  Google Scholar 

  78. Naruse, M.; Aoyagi, S.; Kibayashi, C., New chiral route to (-)-swainsonine via an aqueous acylnitroso cycloaddition approach, J. Org. Chem., 1994, 59, 1358–1364.

    Article  CAS  Google Scholar 

  79. Naruse, M.; Aoyagi, S.; Kibayashi, C., Total synthesis of (-)-pumiliotoxin C by aqueous intramolecular acylnitroso Diels-Alder approach, Tetrahedron Lett., 1994, 35, 9213–9216.

    Article  CAS  Google Scholar 

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Garner, P.P. (1998). Diels-Alder reactions in aqueous media. In: Organic Synthesis in Water. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4950-1_1

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