Carbon−Hydrogen Bond Functionalization using Removable Monodentate Directing Groups



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Chapter 1: 3,5-Dimethylpyrazole was employed as a mono-dentate directing group for palladium-catalyzed ortho-sp2 C−H arylation with aryl iodides. The reaction shows good functional group tolerance and outstanding selectivity for mono-ortho-arylation. Ozonolysis of ortho-arylated arylpyrazoles gave acylated biphenylamines that were further arylated to afford unsymmetrically substituted 2,6-diarylacetanilides. Chapter 2: N-Aminopyridinium ylides were used as mono-dentate directing groups for copper-promoted C−H/N−H coupling of sp2 C−H bonds with pyrazoles, imidazoles, and sulfonamides. Reactions proceed in fluorinated alcohol solvents at elevated temperatures and require use of 1.3−3 equiv of copper(II) acetate. This appears to be the first method for copper-promoted C−H/N−H coupling directed by a removable monodentate auxiliary in absence of added ligands. Chapter 3: N-Aminopyridinium ylides are competent monodentate directing groups for cobalt-catalyzed annulation of sp2 C−H bonds with internal alkynes. Pyridine moiety in ylide serves as an internal oxidant and is cleaved during the reaction. The annulation reactions possess excellent compatibility with heterocyclic substrates, tolerating furan, thiophene, pyridine, pyrrole, pyrazole, and indole functionalities.



C-H bond activation, monodentate directing group


Portions of this document appear in: Kwak, S. H.; Gulia, N.; Daugulis, O. Synthesis of Unsymmetrical 2,6-Diarylanilines by Palladium-Catalyzed C–H Bond Functionalization Methodology. J. Org. Chem. 2018, 83, 5844–5850; and in: Kwak, S. H.; Daugulis, O. N-Aminopyridinium Ylide-Directed, Copper-Promoted Amination of sp2 C–H Bonds. J. Org. Chem. 2019, 84, 13022–13032.