Asymmetric Aldol Reaction Catalyzed by a Heterogenized Proline on a Mesoporous Support. The Role of the Nature of Solvents Elisa G. Doyagu¨ez, Fe´lix Caldero´n, Fe´lix Sa´nchez, and Alfonso Ferna´ndez-Mayoralas*,† Instituto de Quı´mica Orga´ nica General, CSIC, Juan de la CierVa 3, 28006 Madrid, Spain
FIGURE 1. Proline derivative grafted into mesoporous MCM-41. TABLE 1. Solvent Screen for the Aldol Reaction between p-Nitrobenzaldehyde 1 and Dioxanone 2 in the Presence of MCM41-Pro
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A heterogenized (S)-proline on mesoporous support MCM41 catalyzes the asymmetric aldol reaction in a wide range of solvents. The progress of the reaction is dependent on the nature of the solvent. Reactions proceed more efficiently in hydrophilic polar solvents; however, the addition of a small amount of water has a positive effect on the rate and the stereoselectivity of the reaction performed in hydrophobic toluene. The reaction under heterogeneous conditions has also been performed on chiral aldehydes, furnishing useful intermediates for the synthesis of azasugars. There is a growing interest in asymmetric organocatalysis,1 particularly in the use of the amino acid proline2 and its derivatives3 as catalysts for asymmetric aldol additions. The †
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(1) (a) List, B. Chem. Commun. 2006, 819-824. (b) Seayad, J.; List, B. Org. Biomol. Chem. 2005, 3, 719-724. (c) Berkessel, A.; Gro¨ger, H. Asymmetric Organocatalysis; VCH: Weinheim, 2004. (d) List, B. AdV. Synth. Catal. 2004, 9-10, 1021. (e) Houk, K. N.; List, B. Acc. Chem. Res. 2004, 37, 487. (f) Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 2004, 43, 5138-5175. (g) List, B. Synlett 2001, 11, 1675-1686. (2) (a) Enders, D.; Gasperi, T. Chem. Comm. 2007, 88-90. (b) Enders, D.; Grondal, C. Angew. Chem., Int. Ed. 2005, 44, 1210-1212. (c) Northrup, A. B.; MacMillan, D. W. C. Science 2004, 1752-1755. (d) Northrup, A. B.; Mangion, I. K.; Hettche, F.; MacMillan, D. W. C. Angew. Chem., Int. Ed. 2004, 43, 2152-2154. (e) Notz, W.; Tanaka, F.; Barbas, C. F., III. Acc. Chem. Res. 2004, 37, 580-591. (f) Pidathala, C.; Hoang, L.; Vignola, N.; List, B. Angew. Chem., Int. Ed. 2003, 42, 2785-2788. (g) Bøevig, A.; Kumaragurubaran, N.; Jørgensen, K. A. Chem. Commun. 2002, 620-621. (h) Gro¨ger, H.; Wilken, J. Angew. Chem., Int. Ed. 2001, 40, 529-532. (i) Sakthivel, K.; Notz, W.; Bui, T.; Barbas, C. F., III. J. Am. Chem. Soc. 2001, 123, 5260-5267. (j) Notz, W.; List, B. J. Am. Chem. Soc. 2000, 122, 73867387. (k) List, B.; Lerner, R.; Barbas, C. F., III. J. Am. Chem. Soc. 2000, 122, 2395-2396. (3) (a) Palomo, C.; Mielgo, A. Angew. Chem., Int. Ed. 2006, 45, 78767880. (b) Mitchell, C.; Lobb, A.; Ley, S. V. Synlett 2005, 611-614. (c) Saito, S.; Yamamoto, H. Acc. Chem. Res. 2004, 37, 570-579. (d) Berkessel, A.; Koch, B.; Lex, J. AdV. Synth. Catal. 2004, 346, 1141-1146. (e) Hartikka, A.; Arvidsson, P. Tetrahedron: Asymmetry 2004, 15, 1831-1834. (f) Pihko, P. Angew. Chem., Int. Ed. 2004, 43, 2062-2064f. (g) Mase, N.; Tanaka, F.; Barbas, C. F., III Angew. Chem. Int. Ed. 2004, 43, 2420-2423. (h) Tang, Z.; Jiang, F.; Yu, L.-T.; Cui, X.; Gong, L.-Z.; Mi, Ai-Q.; Jiang, Y.Z.; Wu, Y.-D. J. Am. Chem. Soc. 2003, 125, 5262-5263.
1 2 3 4 5 6 7 8 9 10
solvent (log P)a
time (h)
conv.b (%)
anti:synb
eeb (%)
formamide (-1.65) formamide (-1.65)c DMF (-1.00) DMF (-1.00)d MeOH (-0.76) MeCN (-0.33) THF (0.49) t-BuOMe (0.94) CH2Cl2 (1.25) Toluene (2.50)
13 13 61 48 61 96 96 96 96 96
96 93 80 82 46 20 23
