Site‐Selective Functionalization of (sp<sup>3</sup>)C−H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium‐Porphyrin Cofactor

  • Yang Gu
    Department of Chemistry University of California Berkeley CA 94720 USA
  • Sean N. Natoli
    Department of Chemistry University of California Berkeley CA 94720 USA
  • Zhennan Liu
    Department of Chemistry University of California Berkeley CA 94720 USA
  • Douglas S. Clark
    Department of Chemical and Biomolecular Engineering University of California Berkeley CA 94720 USA
  • John F. Hartwig
    Department of Chemistry University of California Berkeley CA 94720 USA

書誌事項

公開日
2019-08-21
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#am
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1002/anie.201907460
公開者
Wiley

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説明

<jats:title>Abstract</jats:title><jats:p>The selective functionalization of one C−H bond over others in nearly identical steric and electronic environments can facilitate the construction of complex molecules. We report site‐selective functionalizations of C−H bonds, differentiated solely by remote substituents, catalyzed by artificial metalloenzymes (ArMs) that are generated from the combination of an evolvable P450 scaffold and an iridium‐porphyrin cofactor. The generated systems catalyze the insertion of carbenes into the C−H bonds of a range of phthalan derivatives containing substituents that render the two methylene positions in each phthalan inequivalent. These reactions occur with site‐selectivity ratios of up to 17.8:1 and, in most cases, with pairs of enzyme mutants that preferentially form each of the two constitutional isomers. This study demonstrates the potential of abiotic reactions catalyzed by metalloenzymes to functionalize C−H bonds with site selectivity that is difficult to achieve with small‐molecule catalysts.</jats:p>

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