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Issue 45, 2019
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A sustainable catalytic enantioselective synthesis of norstatine derivatives

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Norstatine derivatives are of important value in pharmaceutical science. However, their catalytic asymmetric synthesis is rare. We developed a sustainable method via chiral phosphoric acid (CPA)-[Rh(OAc)2]2 co-catalyzed multi-component reactions (MCR) of diazoacetates with alcohol/water and imines. This method allows us to synthesize a library of 45 norstatines with excellent enanotioselectivites and broad substrate scope which includes anti-α-aryl-norstatines 11-1, anti-α-alkyl-norstatines 11-2, syn-α-hydro-norstatines 11-3 and syn-α-aryl-norstatines 11-4. The sustainability of this method lies in the reliable scalability, improved safety, and reusable [Rh(OAc)2]2 catalyst. The synthetic value of norstatine derivatives was demonstrated by preparing oxazolinone 14, ezetimibe analogue 15, and Taxol C-13 chain 16. Mechanistic study reveals that the synergetic catalysis of CPA and [Rh(OAc)2]2 is essential to maintain chemo- and enantioselectivity. Control experiments support the mechanism where the reactions proceed through the trapping of hyper-reactive oxonium ylides with imines. Shortly, we report herein the sustainable catalytic enantioselective synthesis of both syn- and anti-norstatine derivatives. We believe that this method might shed light on the sustainable synthesis of norstatine derivative-based drug candidates.

Graphical abstract: A sustainable catalytic enantioselective synthesis of norstatine derivatives

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Publication details

The article was received on 04 Oct 2019, accepted on 22 Oct 2019 and first published on 24 Oct 2019

Article type: Paper
DOI: 10.1039/C9OB02149C
Org. Biomol. Chem., 2019,17, 9792-9798

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    A sustainable catalytic enantioselective synthesis of norstatine derivatives

    T. Shi, C. Jing, Y. Qian, X. Xu, G. K. R. Alavala, X. Lv and W. Hu, Org. Biomol. Chem., 2019, 17, 9792
    DOI: 10.1039/C9OB02149C

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