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May 9, 2026Accounts of Chemical Research8 citations

Skeletal Editing of Pyridines and Pyrimidines via ANRORC Mechanism

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CLCong LvSLShun LiYSYonglin Shi

Key Points

  • This work aims to outline a modular system for the skeletal editing of pyridines and pyrimidines via the ANRORC mechanism.
  • Rational design of activators such as alkyl, vinyl, benzyl, and dinitrophenyl groups.
  • Incorporation of diverse nucleophiles like O-, C-, and N-based species.
  • Generation of varied open-chain intermediates such as Zincke aldehydes and vinamidinium salts for multiple reaction paths.
  • Efficient contraction of pyridine rings to functionalized pyrroles observed.
  • Degenerate ring transformations of pyridines were successfully achieved.
  • Transformation of pyrimidines into diverse nitrogen-containing heterocycles via vinamidinium salt intermediates

Abstract

-heteroarenes. Through the rational design of activators (including alkyl, vinyl, benzyl, dinitrophenyl and Tf groups) and the incorporation of diverse nucleophiles (O-, C-, and N-based), we have established a modular system capable of generating a range of key open-chain intermediates such as Zincke aldehydes, azatrienes (including Zincke imines), streptocyanines, and vinamidinium salts. Strategic modification of these versatile intermediates using a wide range of electrophilic, amphiphilic, or dipolar reagents enables multiple editing paradigms, including efficient pyridine ring contractions to functionalized pyrroles, degenerate ring transformations of pyridines with concurrent core functionalization, and denitrogenative annulation of pyridine to arene dialdehydes or thiophene motifs. Moreover, it facilitates the transformation of pyrimidines into diverse nitrogen-containing heterocycles via vinamidinium salt intermediates. In this Account, we systematically summarize our work on skeletal editing using tunable Zincke intermediates generated via the ANRORC pathway, with particular emphasis on mechanistic understanding, substrate scope, and synthetic applications. By outlining prospective research directions, we anticipate this Account will set the stage for future exploration of the ANRORC strategy in skeletal editing of heterocycles, promote the discovery of novel reactivity patterns, and thereby contribute to further progress in this dynamic field.

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Cite This Study

Lv et al. (2026) studied this question.

synapsesocial.com/papers/69fed123b9154b0b82878613https://doi.org/10.1021/acs.accounts.6c00077
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