Diastereoselectivity in a cyclic secondary amine catalyzed asymmetric Mannich reaction: a model rationalization from DFT studies

作者：Shu, Siwei; Liu, Zhao; Li, Yukui; Ke, Zhuofeng^*; Liu, Yan^*

来源：Organic Chemistry Frontiers, 2018, 5(14): 2148-2157.

DOI：10.1039/c8qo00424b

• MOLECULAR-ORBITAL METHODS
• GAUSSIAN-TYPE BASIS
• N-BOC-IMINES
• STEREOCONTROLLED SYNTHESIS
• ENANTIOSELECTIVE SYNTHESIS
• DENSITY FUNCTIONALS
• ORGANIC-MOLECULES
• ALPHA-AMINO
• PYRROLIDINE
• DERIVATIVES

A variation in diastereoselectivity is rationalized for cyclic secondary amine catalyzed asymmetric Mannich reactions, by systematic DFT studies on a series of representative catalysis systems. Computational results well explain the experimentally observed stereoselectivities for all the systems. Structural factors that influence the stereoselectivity are elucidated based on transition state analysis. Three structural parameters including two lengths L-1 and L-2, and a dihedral angle D-1 of intermediates are found to be able to concisely correlate the relationship between structures and diastereoselectivities. A quantitative structure-stereoselectivity relationship (QSSR) model containing these three parameters is proposed to correlate the diastereoselectivity of Mannich reactions catalyzed by cyclic secondary amines. The model rationalization study could serve as an interesting example to understand the stereoselectivities and to advance catalyst design in asymmetric organocatalysis.

• 出版日期2018-7-21
• 单位中山大学; 广东工业大学