A Bulky Chiral N‐Heterocyclic Carbene Nickel Catalyst Enables Enantioselective C−H Functionalizations of Indoles and Pyrroles

• Published in: Angewandte Chemie International Edition Vol. 58; no. 32; pp. 11044 - 11048
• Main Authors: Diesel, Johannes, Grosheva, Daria, Kodama, Shota, Cramer, Nicolai
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 05.08.2019; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: asymmetric catalysis; Chemistry; Chemistry, Multidisciplinary; chiral NHC ligands; C−H activation; Enantiomers; heterocycles; Indoles; Nickel; Physical Sciences; Pyrroles; Science & Technology; Selectivity; nickel; ACTIVATION; ANNULATION; ASYMMETRIC FUNCTIONALIZATION; ALKYLATION; ARYLATION; asymmetric catalysis; chiral NHC ligands; ALKENES; EFFICIENT ACCESS; C-H activation; heterocycles; LIGAND; HYDROHETEROARYLATION; HYDROARYLATION; C−H activation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201904774

An enantioselective nickel(0)‐catalyzed C−H functionalization of indoles and pyrroles that does not require the typical Lewis basic directing groups is disclosed. The reaction provides access to valuable tetrahydropyridoindoles and tetrahydroindolizines in high yields and enantioselectivity under mild reaction conditions. The process is characterized by a clear endo‐cyclization preference to yield the sought‐after six‐membered‐ring products. Key for the success of the activation and selectivity in the cyclization was the development of a novel chiral SIPr carbene ligand analogue with very bulky flanking groups. The incredible bulk: An enantioselective directing‐group‐free Ni0‐catalyzed C−H functionalization of indoles provides access to tetrahydropyridoindoles and tetrahydroindolizines in high yields and enantioselectivity under mild reaction conditions. The activation and selective cyclization are enabled by a novel chiral SIPr carbene ligand analogue with very bulky flanking groups.