Simple, inexpensive, and facile l-prolinamide used as a recyclable organocatalyst for highly efficient large-scale asymmetric direct aldol reactions

Abstract

In order to discover a simple, inexpensive, and efficient route to obtain highly enantiomerically enriched anti-aldol products for applications in industry, a series of prolinamides 1-5 with different carbocyclic rings have been synthesized from achiral cycloalkylamine, and prolinamides 6-9 have been synthesized from aniline with different substituents. The organocatalysts obtained catalyzed the asymmetric aldol reaction and showed that no matter carbocyclic rings or aromatic rings were found to play a significant role in the formation of the aldol products. Moreover, the prolinamide 6 exhibited efficient catalytic activity in the asymmetric aldol reaction only with 5 mol % catalyst loading and 4 equiv of ketone, and afforded aldol products in high diastereoselectivity (up to anti/syn 99:1) and enantioselectivity (99%) and significantly enhanced the reaction yield (99%). These results were much better than l-proline-3-nitroanilide which had the strongest electron-withdrawing group on the aromatic ring. Furthermore, catalyst 6 can be easily recovered and reused, without a significant decrease of enantioselectivity after five cycles. This inexpensive, simple, and recyclable catalyst can be efficiently used in large-scale reactions with the enantioselectivities being maintained at the same level, which offers a great possibility for application in industry. © 2011 Elsevier Ltd. All rights reserved.