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.
Tang
Zhuo
Z
Key Laboratory for Asymmetric Synthesis and Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, 610041, China.
Jiang
Fan
F
Yu
Luo-Ting
LT
Cui
Xin
X
Gong
Liu-Zhu
LZ
Mi
Ai-Qiao
AQ
Jiang
Yao-Zhong
YZ
Wu
Yun-Dong
YD