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Transition-Metal-Catalyzed C-H Bond Activation for the Formation of C-C Bonds in Complex Molecules

Research output: Contribution to Journal/MagazineReview articlepeer-review

  • Jamie H. Docherty
  • Thomas M. Lister
  • Gillian Mcarthur
  • Michael T. Findlay
  • Pablo Domingo-Legarda
  • Jacob Kenyon
  • Shweta Choudhary
  • Igor Larrosa
<mark>Journal publication date</mark>28/06/2023
<mark>Journal</mark>Chemical Reviews
Issue number12
Number of pages69
Pages (from-to)7692-7760
Publication StatusPublished
Early online date10/05/23
<mark>Original language</mark>English


Site-predictable and chemoselective C-H bond functionalization reactions offer synthetically powerful strategies for the step-economic diversification of both feedstock and fine chemicals. Many transition-metal-catalyzed methods have emerged for the selective activation and functionalization of C-H bonds. However, challenges of regio- and chemoselectivity have emerged with application to highly complex molecules bearing significant functional group density and diversity. As molecular complexity increases within molecular structures the risks of catalyst intolerance and limited applicability grow with the number of functional groups and potentially Lewis basic heteroatoms. Given the abundance of C-H bonds within highly complex and already diversified molecules such as pharmaceuticals, natural products, and materials, design and selection of reaction conditions and tolerant catalysts has proved critical for successful direct functionalization. As such, innovations within transition-metal-catalyzed C-H bond functionalization for the direct formation of carbon-carbon bonds have been discovered and developed to overcome these challenges and limitations. This review highlights progress made for the direct metal-catalyzed C-C bond forming reactions including alkylation, methylation, arylation, and olefination of C-H bonds within complex targets.