Novel Small Organic Molecules for a Highly Enantioselective Direct Aldol Reaction

• Published in: Journal of the American Chemical Society Vol. 125; no. 18; pp. 5262 - 5263
• Main Authors: Tang, Zhuo, Jiang, Fan, Yu, Luo-Ting, Cui, Xin, Gong, Liu-Zhu, Mi, Ai-Qiao, Jiang, Yao-Zhong, Wu, Yun-Dong
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 07.05.2003; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Exact sciences and technology; Kinetics and mechanisms; Organic chemistry; Physical Sciences; Reactivity and mechanisms; Science & Technology; KETONES; ROUTE; L-PROLINE; COMPLEX; ASYMMETRIC ALPHA-AMINATION; ATOM ECONOMY; AMINO-ACIDS; ALDEHYDES; CATALYSTS; Catalytic reaction; Enantioselectivity; Reaction path; Benzaldehyde; Theoretical study; Hartree Fock method; Experimental study; Aldol condensation; Chiral auxiliary; Homogeneous catalysis; Transition state; Asymmetric reaction; Carboxamide; Catalyst activity; Acetone
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja034528q

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.