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This paper also includes an excellent introduction to the state-of-the-art methods for the synthesis of α-substituted acroleins. (7) For experimental examples with more complex aldehydes, see: (a) Yoshida, K.; Grieco, P. J. Org. Chem. 1984, 49, 5257-5260.
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33645030162
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(c) In our hands, these protocols often failed to give any useful yields of the product, especially with aldehydes prone to polymerization.
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(a) Hon, Y.-S.; Chang, F.-J.; Lu, L. J. Chem. Soc., Chem. Commun. 1994, 2041-2042.
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Recently, an organocatalytic method for the synthesis of α,β-unsaturated ketones was reported: (a) Wang, W.; Mei, Y.; Li, H.; Wang, J. Org. Lett. 2005, 7, 601-604.
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(a) Córdova and co-workers have reported that reactions between aldehydes with formaldehyde under proline catalysis afford hydroxymethylated aldehydes enantioselectively. This would suggest that the reaction proceeds via an aldol-dehydration mechanism. However, in our hands reactions of aldehydes with aqueous formaldehyde only afforded the corresponding unsaturated aldehydes. Casas, J.; Sundén, H.; Córdova, A. Tetrahedron Lett. 2004, 45, 6117-6119.
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23944510751
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(e) For an oxa-Michael/aldol/dehydration protocol for the preparation of α,β-substituted aldehydes, see: Habib-Sahmani, H.; Hacini, S.; Bories, C.; Faure, R.; Rodriguez, J. Synthesis 2005, 2151-2156.
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33645022586
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note
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With simple amines, raising the temperature afforded higher conversions to the product. However, polymerization and loss of product by evaporation resulted in erratic and irreproducible yields in the case of methacrolein.
-
-
-
-
49
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33645030054
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note
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With catalyst 4, 5-hydroxyvaleraldehyde gave ca. 55-60% yield of the α-methylenation product after 24 h reaction time, accompanied by significant decomposition. 2-Deoxyribose afforded less than 5% of the product under similar conditions.
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