title: Enantioselective direct aldol reactions catalyzed by L-prolinamide derivatives.
abstract: l-Prolinamides 2, prepared from l-proline and simple aliphatic and aromatic amines, have been found to be active catalysts for the direct aldol reaction of 4-nitrobenzaldehyde with neat acetone at room temperature. They give moderate enantioselectivities of up to 46% enantiomeric excess (ee). The enantioselectivity increases as the amide N-H becomes a better hydrogen bond donor. l-Prolinamides 3, derived from the reaction of l-proline with alpha,beta-hydroxyamines such that there is a terminal hydroxyl group, show more efficient catalysis and higher enantioselectivities. In particular, catalyst 3h, prepared from l-proline and (1S,2S)-diphenyl-2-aminoethanol, exhibits high enantioselectivities of up to 93% ee for aromatic aldehydes and up to >99% ee for aliphatic aldehydes under -25 degrees C. Model reactions of benzaldehyde with three enamines derived from the condensation of prolinamides with acetone have been studied by quantum mechanics calculations. The calculations reveal that the amide N-H and the terminal hydroxyl groups form hydrogen bonds with the benzaldehyde substrate. These hydrogen bonds reduce the activation energy and cause high enantioselectivity. Our results suggest a new strategy in the design of new organic catalysts for direct asymmetric aldol reactions and related transformations.
authors.affiliation: Key Laboratory for Asymmetric Synthesis and Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Tang
authors.forename: Fan
authors.initials: F
authors.lastname: Jiang
authors.forename: Xin
authors.initials: X
authors.lastname: Cui
authors.forename: Liu-Zhu
authors.initials: LZ
authors.lastname: Gong
authors.forename: Ai-Qiao
authors.initials: AQ
authors.lastname: Mi
authors.forename: Yao-Zhong
authors.initials: YZ
authors.lastname: Jiang
authors.forename: Yun-Dong
authors.initials: YD
authors.lastname: Wu