Theoretical Studies of the Asymmetric Binary-Acid-Catalyzed tert-Aminocyclization Reaction: Origins of the Cinline image[BOND]H Activation and Stereoselectivity

Authors

  • Dr. Long Zhang,

    1. Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key of Molecular Recognition and Function Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China), Fax: (+86) 10-62554449 http://luosz.iccas.ac.cn
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  • Liujuan Chen,

    1. Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key of Molecular Recognition and Function Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China), Fax: (+86) 10-62554449 http://luosz.iccas.ac.cn
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  • Dr. Jian Lv,

    1. Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key of Molecular Recognition and Function Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China), Fax: (+86) 10-62554449 http://luosz.iccas.ac.cn
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  • Prof. Jin-Pei Cheng,

    1. Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key of Molecular Recognition and Function Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China), Fax: (+86) 10-62554449 http://luosz.iccas.ac.cn
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  • Prof. Sanzhong Luo

    Corresponding author
    1. Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key of Molecular Recognition and Function Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China), Fax: (+86) 10-62554449 http://luosz.iccas.ac.cn
    • Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key of Molecular Recognition and Function Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China), Fax: (+86) 10-62554449 http://luosz.iccas.ac.cn

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Abstract

A mechanistic study of the tert-aminocyclization reaction was performed by using DFT calculations and labeling experiments. The results showed that the reaction proceeded through a rate-limiting-, stereospecific-, and suprafacial 1,5-H-transfer pathway, followed by a barrier-less C[BOND]C bond formation. The mode of stereocontrol for facial selection could be ruled out owing to the high activation energy of C[BOND]N bond rotation. The intrinsic feature of this Lewis acid activation was found to be the activation of the LUMO, as well as an intermediate-stabilization effect. The catalytically active species was believed to be a 1:1 complex of phosphoric acid and MgCl2, which was stabilized by a H⋅⋅⋅Cl hydrogen bond. The chiral catalytic complex selectively recognizes and activates one of the two helical conformations of substrate A, required for 1,5-suprafacial H-transfer, which dictates the stereoselectivity of the forming products.

Abstract

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