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October 7, 2025Organic Letters5 citations

Rh-Catalyzed C–H Activation, 5 + 2 Cycloaddition/Oxidative for the Synthesis of Highly Functionalized Benzofpyrazolo1,5-a1,3diazepin-6-ones

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BSBi−Na ShaoJSJiaqi ShaoQZQingsheng Zhao

Key Points

  • The method produces benzo[f]pyrazolo[1,5-a][1,3]diazepin-6-ones through innovative c-h activation and cycloaddition.
  • Major features include the formation of three bonds (C-C, C=N, C=O) in a single step, enhancing efficiency.
  • Utilizing sulfoxonium ylides and various catalysts showcases a unique synthesis pathway for complex structures.
  • Significant implications for developing polycyclic natural products suggest extensive applications in medicinal chemistry.

Abstract

We developed a protocol for the synthesis of highly functionalized benzofpyrazolo1,5-a1,3diazepin-6-ones 3 (BPDOs) from 1-aryl-1H-pyrazol-5-amine derivatives using sulfoxonium ylides. This strategy involved Rh-catalyzed C-H activation and a rare 5 + 2 cycloaddition, with water participating in the capture of the intermediate to form an alcohol that is further oxidized into a seven-membered cyclic ketone structure, requiring the heating of a mixture of substrates 1 with 2 and isopropanol, catalyzed by Cp*RhCl22, with Cu(OAc)2 and AgSbF6 acting as oxidants and anion exchange agents, and NaOAc serving as a buffering system. As a result, a series of BPDOs 3 were produced by forming three bonds (1 C-C, 1 C═N, and 1 C═O bond) in a single step. This protocol achieved an example of C-H bond activation forming a seven-membered cyclic structure with Rh(III). This strategy enables the synthesis of various rare complex structures, including polycyclic natural products with a benzo1,3diazepin-6-one scaffold, which offers a library of biologically active compounds accessible through combinatorial and parallel one-pot reactions.

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Cite This Study

Shao et al. (2025) studied this question.

synapsesocial.com/papers/68e585d0b1e78cc4e5f46743https://doi.org/10.1021/acs.orglett.5c02561
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