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Transformation of l-phenylalanine to (S)-indoline-2-carboxylic acid without group-protection

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Abstract

(S)-Indoline-2-carboxylic acid was synthesized by use of a nitro amination approach with l-phenylalanine as chiral pool. The first step of the synthesis was nitration of l-phenylalanine, with urea nitrate (UN)/H2SO4 as nitrating reagent, to give 2,4-dinitro-l-phenylalanine in 75.7 % yield in one-pot synthesis and 69.1 % yield by step-wise nitration. Intramolecular nitro amination of 2,4-dinitro-l-phenylalanine gave (S)-6-nitro-indoline-2-carboxylic acid in 65.7 % yield and more than 99.5 % enantiomeric excess (ee). The title compound, (S)-indoline-2-carboxylic acid, was obtained in 85.9 % yield and high ee by one-pot transformation of (S)-6-nitroindoline-2-carboxylic acid. The total synthesis consisted of three operations and gave the title compound in 42 % yield and more than 99.5 % ee.

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Acknowledgments

We gratefully acknowledge the generous financial support of a grant from the National Natural Science Foundation of China (nos. 20776127 and 21172105).

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Authors and Affiliations

  1. College of Chemistry and Chemical Engineering, Luoyang Normal University, Luoyang, 471022, China

    Jin-Qiang Liu, Baoming Ji & Bang-Tun Zhao

  2. Department of Chemical Engineering, Zhejiang University, Hangzhou, 310027, China

    Xin-Zhi Chen

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  1. Jin-Qiang Liu
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Correspondence to Jin-Qiang Liu.

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Liu, JQ., Chen, XZ., Ji, B. et al. Transformation of l-phenylalanine to (S)-indoline-2-carboxylic acid without group-protection. Res Chem Intermed 39, 1143–1152 (2013). https://doi.org/10.1007/s11164-012-0673-z

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