Catalytic Asymmetric 1,2-Addition of α-Isothiocyanato Phosphonates: Synthesis of Chiral β-Hydroxy- or β-Amino-Substituted α-Amino Phosphonic Acid Derivatives

Authors

  • Yi-Ming Cao,

    1. Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000 (China)
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  • Fang-Fang Shen,

    1. Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000 (China)
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  • Fu-Ting Zhang,

    1. Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000 (China)
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  • Jin-Long Zhang,

    1. Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000 (China)
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  • Prof. Dr. Rui Wang

    Corresponding author
    1. Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000 (China)
    • Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000 (China)

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  • We are grateful for grants from the National Natural Science Foundation of China (Nos. 91213302, 20932003 and 21272102), the Key National S&T Program “Major New Drug Development” of the Ministry of Science and Technology of China (2012ZX09504001-003) and the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT: IRT1137).

Abstract

α-Amino phosphonic acid derivatives are considered to be the most important structural analogues of α-amino acids and have a very wide range of applications. However, approaches for the catalytic asymmetric synthesis of such useful compounds are very limited. In this work, simple, efficient, and versatile organocatalytic asymmetric 1,2-addition reactions of α-isothiocyanato phosphonate were developed. Through these processes, derivatives of β-hydroxy-α-amino phosphonic acid and α,β-diamino phosphonic acid, as well as highly functionalized phosphonate-substituted spirooxindole, can be efficiently constructed (up to 99 % yield, d.r. >20:1, and >99 % ee). This novel method provides a new route for the enantioselective functionalization of α-phosphonic acid derivatives.

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