Modular Chiral N-Heterocyclic Carbene Ligands for the Nickel-Catalyzed Enantioselective C–H Functionalization of Heterocycles

Authors

  • Johannes Diesel Ecole Polytechnique Fédérale de Lausanne, EPFL SB ISIC LCSA, BCH 4305, CH-1015 Lausanne
  • Nicolai Cramer Ecole Polytechnique Fédérale de Lausanne, EPFL SB ISIC LCSA, BCH 4305, CH-1015 Lausanne;, Email: nicolai.cramer@epfl.ch

DOI:

https://doi.org/10.2533/chimia.2020.278

Keywords:

Asymmetric catalysis, Carbenes, C–h functionalization, Nhc, Nickel

Abstract

N-Heterocyclic carbenes (NHCs) are the ligands of choice in a large variety of transformations entailing different transition metals. However, the number and variety of chiral NHCs suitable as stereo-controlling ligands in asymmetric catalysis remains limited. Herein we highlight the introduction of a modular NHC ligand family, consisting of a chiral version of the widely used IPr ligand. These chiral NHC ligands were applied in the nickel-catalyzed enantioselective C–H functionalization of N-heterocycles. Nickel-NHC catalysis unlocked the stereoselective C–H annulation of 2- and 4-pyridones, delivering fused bicyclic compounds found in many biologically active compounds. Applying a bulky, yet flexible ligand scaffold enabled the highly enantioselective C–H functionalization of pyridones under mild conditions. The introduction of a bulky chiral SIPr analogue enabled the nickel-catalyzed enantioselective C–H functionalization of indoles, yielding valuable tetrahydropyridoindoles. Additionally, pyrrolopyridines, pyrrolopyrimidines and pyrroles were efficiently functionalized, delivering chiral annulated azoles.

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Published

2020-04-29

How to Cite

[1]
J. Diesel, N. Cramer, Chimia 2020, 74, 278, DOI: 10.2533/chimia.2020.278.