Novel small organic molecules for a highly enantioselective direct aldol reaction.
Novel organic molecules containing an l-proline amide moiety and a terminal hydroxyl for catalyzing direct asymmetric aldol reactions of aldehydes in neat acetone are designed and prepared. Catalyst 3d, 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. A theoretical study of transition structures demonstrates the important role of the terminal hydroxyl group in the catalyst in the stereodiscrimination. Our results suggest a new strategy in the design of new organic catalysts for direct asymmetric aldol reactions and related transformations because plentiful chiral resources containing multi-hydrogen bond donors, for example, peptides, might be adopted in the design.
Key Laboratory for Asymmetric Synthesis and Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, 610041, China.
Zhuo
Z
Tang
Fan
F
Jiang
Luo-Ting
LT
Yu
Xin
X
Cui
Liu-Zhu
LZ
Gong
Ai-Qiao
AQ
Mi
Yao-Zhong
YZ
Jiang
Yun-Dong
YD
Wu