A Chiral Lewis-Acid-Catalyzed Diels−Alder Reaction. Water-Enhanced Enantioselectivity

Abstract

Water is becoming increasingly popular as a medium for organic reactions.1 Apart from the obvious economic and environmental benefits,2 the aqueous medium can have favorable effects on many organic transformations.3 In the field of Lewisacid catalysis, the use of water is still in its infancy.4 Accordingly, reports on Lewis-acid catalysis of Diels-Alder reactions in water5 or mixtures of organic solvents with small amounts of water6 are scarce. Examples of enantioselectiVe Lewis-acid-catalyzed Diels-Alder reactions in water have been completely lacking to date. In organic solvents, enantioselective Lewis-acid catalysis of Diels-Alder reactions has been studied extensively.7 The choice of the solvent for these reactions is rather limited. Donating solvents are generally avoided since they exert detrimental effects on rate and enantioselectivity.8 Nevertheless, on the basis of our previous work on Lewis-acid catalysis of Diels-Alder reactions in water,5a,b we envisaged that even in aqueous media enantioselective catalysis should be possible. In recent studies,5a,b we have already shown that water can have a beneficial effect on the rate of the Lewis-acid-catalyzed DielsAlder reaction of 3-phenyl-1-(2-pyridyl)-2-propen-1-one (1) with cyclopentadiene (2) (Scheme 1). We now report that for this reaction enantioselectivity can be induced by coordinating chiral commercially available R-amino acids to a catalytically active metal ion. Derivatives of R-amino acids have already been reported to induce large enantioselectivities in Diels-Alder reactions in organic solvents.8a,9 In the presence of 10 % percent of copper(II) complexes of glycine, L-valine, L-leucine, L-phenylalanine, L-tyrosine, L-tryptophan, and NR-methyl-L-tryptophan (L-abrine), the Diels-Alder adduct 3 is obtained after 48 h in yields generally exceeding 90%.10 Most interestingly, enantioselectivity is observed for the chiral ligands (Table 1). With L-abrine, an enantiomeric excess (ee) of 74% can be achieved. The catalyst solution can be reused without decrease in enantioselectivity. To the best of our knowledge, this is the first example of an enantiomeric excess in a chiral Lewis-acid-catalyzed reaction in water. Significant enantioselectivities are observed exclusively for the R-amino acids containing aromatic side groups. This suggests that arene-arene interactions are important in discriminating between the two pathways leading to the enantiomeric DielsAlder adducts. The importance of these interactions was further assessed by examining the effect of the R-amino acid ligands on the following: (1) the equilibrium constants (K1 in Scheme 1) for binding of the dienophile to the copper-ligand complex and (2) the second-order rate constants (k2) for reaction of 2 with the thus-formed complex. The results are shown in Table 1. When compared to the aquo complex, the presence of the aliphatic R-amino acids glycine, L-valine, and L-leucine at the copper center causes a decrease of the equilibrium constants for binding of 1 to this copper ion. Presumably, this effects is a consequence of the reduction of the number of coordination sites available on the copper center in combination with a reduction of the Lewis acidity of the metal ion as a result of the presence of the Lewisbasic R-amino acid ligand. Interestingly, for the aromatic R-amino acids an additional and counteractive effect is operative, which raises the equilibrium (1) (a) Li, C. Chem. ReV. 1993, 93, 2023. (b) Lubineau, A. Chem. Ind. 1996, 123. (c) Cornils, B.; Herrmann, W. A.; Eckl, R. W. J. Mol. Catal., A Chem. 1997, 116, 27. (d) Organic Synthesis in Water; Grieco, P. A., Ed.; Blackie Academic and Professional: London, 1998. (2) Cornils, B.; Wiebus, E. Recl. TraV. Chim. Pays-Bas 1996, 115, 211. (3) Particularly the Diels-Alder reaction benefits strongly from the use of water as the solvent, as was discovered by Breslow (Rideout, D. C.; Breslow, R. J. J. Am. Chem. Soc. 1980, 102, 7816). For recent references, see: (a) Otto, S.; Blokzijl, W.; Engberts, J. B. F. N. J. Org. Chem. 1994, 59, 5372. (b) Engberts, J. B. F. N. Pure Appl. Chem. 1995, 67, 823. (4) Engberts, J. B. F. N.; Feringa, B. L.; Keller, E.; Otto, S. Recl. TraV. Chim. Pays-Bas 1996, 115, 457. (5) (a) Otto, S.; Engberts, J. B. F. N. Tetrahedron Lett. 1995, 36, 2645. (b) Otto, S.; Bertoncin, F.; Engberts, J. B. F. N. J. Am. Chem. Soc. 1996, 118, 7702. (c) Loh, T.; Pei, J.; Lin, M. J. Chem. Soc., Chem. Commun. 1996, 2315. (d) Yu, L.; Chen, D.; Wang, P. G. Tetrahedron Lett. 1996, 37, 2169. (e) Yu, L.; Li, J.; Ramirez, J.; Chen, D.; Wang, P. G. J. Org. Chem. 1997, 62, 903. (f) Zhu, Z.; Espenson, J. H. J. Am. Chem. Soc. 1997, 119, 3507. (6) (a) Kobayashi, S.; Hachiya, I.; Araki, M.; Ishitani, H. Tetrahedron Lett. 1993, 34, 3755. (b) Kobayashi, S. Synlett 1994, 689. (7) For a review, see: Kagan, H. B.; Riant, O. Chem. ReV. 1992, 92, 1007. (8) (a) Sartor, D.; Saffrich, J.; Helmchen, G.; Richards, C. J.; Lambert, H. Tetrahedron: Asymmetry 1991, 2, 639. (b) Nevalainen, V. Tetrahedron: Asymmetry 1991, 2, 827. (9) (a) Takasu, M.; Yamamoto, H. Synlett 1990, 194. (b) Sartor, D.; Saffrich, J.; Helmchen, G. Synlett 1990, 197. (c) Corey, E. J.; Loh, T. J. Am. Chem. Soc. 1991, 113, 8966. (d) Corey, E. J.; Loh, T.; Roper, T. D.; Azimioara, M. D.; Noe, M. J. Am. Chem. Soc. 1992, 114, 8290. (10) In a typical procedure a solution of 0.175 mmol of L-abrine and 0.175 mmol of NaOH in 1 mL of water was added to a solution of 0.100 mmol of Cu(NO3)2 in 100 mL of water. The pH was adjusted to 6-6.5. The catalyst solution was cooled to 0 °C, and a solution of 1.0 mmol of 1 in a minimal amount of ethanol was added, together with 2.0 mmol of 2. After 48 h of stirring at 0 °C, the reaction mixture was extracted with ether affording 0.94 mmol (94%) of 3. All attempts to determine the absolute configuration of 3 and several derivatives thereof by X-ray diffraction have been as yet unsuccessful, due to problems in obtaining suitable crystals. Scheme 1 4238 J. Am. Chem. Soc. 1998, 120, 4238-4239