Highly efficient direct a larger-scale aldol reactions catalyzed by a flexible prolinamide based-metal Lewis acid bifunctional catalyst in the presence of water

In this work, four prolinamide-based organocatalysts were readily synthesized and applied to the asymmetric direct aldol reactions of ketones and aromatic aldehydes in the presence of water. When TFA was used as an acidic additive, 10 mol % loading of 1c afforded aldol products with good diastereoselectivity of up to 91/9 and enantioselectivity of up to 85%. When ZnCl2 was added as a metal Lewis acid additive, the aldol product could be obtained with up to 99/1 dr and 96% ee. This novel prolinamide based-metal Lewis acid bifunctional organocatalyst 1c can be efficiently used in a larger-scale reactions with the enantioselectivities being maintained at the same level, which offers a great possibility for application in industry.

In this paper, four metal Lewis acid-enamine bifunctional catalysts were applied to the asymmetric direct aldol reactions. The products could be obtained with up to 99:1 (anti/syn) and 96% ee. Catalyst 1c can be efficiently used in a larger-scale reaction in the presence of water.Figure optionsDownload as PowerPoint slideHighlights
► A novel class of metal Lewis acid-enamine bifunctional catalysts were obtained.
► All of the catalysts 1a–d are synthesized in a facile manner.
► The reaction were studied in the presence of water for the first time.
► The aldol products could be obtained with up to 99:1 (anti/syn) and 96% ee.
► The catalyst 1c can be efficiently used in a larger-scale reactions.