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Enantioselective Formal C(sp3)-H Bond Activation in the Synthesis of Bioactive Spiropyrazolone Derivatives.
Angew Chem Int Ed Engl. 2019 01 02; 58(1):307-311.AC

Abstract

Herein, we report the first enantioselective annulation of α-arylidene pyrazolones through a formal C(sp3)-H activation under mild conditions enabled by highly variable RhIII -Cpx catalysts. The method has a wide substrate scope and proceeds with good to excellent yields and enantioselectivities. Its synthetic utility was demonstrated by the late-stage functionalization of drugs and natural products as well as the preparation of enantioenriched [3]dendralenes. Preliminary biological investigations also identified the spiropyrazolones as a novel class of Hedgehog pathway inhibitors.

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Authors+Show Affiliations

Li H
Max-Planck-Institut für Molekulare Physiologie, Abteilung Chemische Biologie, Otto-Hahn-Straβe 11, 44227, Dortmund, Germany.
Gontla R
Max-Planck-Institut für Molekulare Physiologie, Abteilung Chemische Biologie, Otto-Hahn-Straβe 11, 44227, Dortmund, Germany.
Flegel J
Max-Planck-Institut für Molekulare Physiologie, Abteilung Chemische Biologie, Otto-Hahn-Straβe 11, 44227, Dortmund, Germany. Technische Universität Dortmund, Fakultät Chemie und Chemische Biologie, Otto-Hahn-Straβe 4a, 44227, Dortmund, Germany.
Merten C
Ruhr-Universität Bochum, Lehrstuhl für Organische Chemie II, Universitätsstraβe 150, 44801, Bochum, Germany.
Ziegler S
Max-Planck-Institut für Molekulare Physiologie, Abteilung Chemische Biologie, Otto-Hahn-Straβe 11, 44227, Dortmund, Germany.
Antonchick AP
Max-Planck-Institut für Molekulare Physiologie, Abteilung Chemische Biologie, Otto-Hahn-Straβe 11, 44227, Dortmund, Germany. Technische Universität Dortmund, Fakultät Chemie und Chemische Biologie, Otto-Hahn-Straβe 4a, 44227, Dortmund, Germany.
Waldmann H
Max-Planck-Institut für Molekulare Physiologie, Abteilung Chemische Biologie, Otto-Hahn-Straβe 11, 44227, Dortmund, Germany. Technische Universität Dortmund, Fakultät Chemie und Chemische Biologie, Otto-Hahn-Straβe 4a, 44227, Dortmund, Germany.

MeSH

CatalysisMolecular StructureSpiro CompoundsStereoisomerism

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30511449

Citation

Li, Houhua, et al. "Enantioselective Formal C(sp3)-H Bond Activation in the Synthesis of Bioactive Spiropyrazolone Derivatives." Angewandte Chemie (International Ed. in English), vol. 58, no. 1, 2019, pp. 307-311.
Li H, Gontla R, Flegel J, et al. Enantioselective Formal C(sp3)-H Bond Activation in the Synthesis of Bioactive Spiropyrazolone Derivatives. Angew Chem Int Ed Engl. 2019;58(1):307-311.
Li, H., Gontla, R., Flegel, J., Merten, C., Ziegler, S., Antonchick, A. P., & Waldmann, H. (2019). Enantioselective Formal C(sp3)-H Bond Activation in the Synthesis of Bioactive Spiropyrazolone Derivatives. Angewandte Chemie (International Ed. in English), 58(1), 307-311. https://doi.org/10.1002/anie.201811041
Li H, et al. Enantioselective Formal C(sp3)-H Bond Activation in the Synthesis of Bioactive Spiropyrazolone Derivatives. Angew Chem Int Ed Engl. 2019 01 2;58(1):307-311. PubMed PMID: 30511449.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enantioselective Formal C(sp3)-H Bond Activation in the Synthesis of Bioactive Spiropyrazolone Derivatives. AU - Li,Houhua, AU - Gontla,Rajesh, AU - Flegel,Jana, AU - Merten,Christian, AU - Ziegler,Slava, AU - Antonchick,Andrey P, AU - Waldmann,Herbert, Y1 - 2018/12/04/ PY - 2018/09/25/received PY - 2018/12/5/pubmed PY - 2020/8/1/medline PY - 2018/12/5/entrez KW - C−H activation KW - Hedgehog pathway inhibitors KW - asymmetric catalysis KW - rhodium KW - spiropyrazolones SP - 307 EP - 311 JF - Angewandte Chemie (International ed. in English) JO - Angew Chem Int Ed Engl VL - 58 IS - 1 N2 - Herein, we report the first enantioselective annulation of α-arylidene pyrazolones through a formal C(sp3)-H activation under mild conditions enabled by highly variable RhIII -Cpx catalysts. The method has a wide substrate scope and proceeds with good to excellent yields and enantioselectivities. Its synthetic utility was demonstrated by the late-stage functionalization of drugs and natural products as well as the preparation of enantioenriched [3]dendralenes. Preliminary biological investigations also identified the spiropyrazolones as a novel class of Hedgehog pathway inhibitors. SN - 1521-3773 UR - https://www.unboundmedicine.com/medline/citation/30511449/Enantioselective_Formal_C_sp3__H_Bond_Activation_in_the_Synthesis_of_Bioactive_Spiropyrazolone_Derivatives_ DB - PRIME DP - Unbound Medicine ER -