Donets, Pavel A.Cramer, Nicolai2015-02-202015-02-202015-02-20201510.1002/anie.201409669https://infoscience.epfl.ch/handle/20.500.14299/111281WOS:000347238800045The 1,6-annulated 2-pyridone motif is found in many biologically active compounds and its close relation to the indolizidine and quinolizidine alkaloid core makes it an attractive building block. A nickel-catalyzed CH functionalization of 2-pyridones and subsequent cyclization affords 1,6-annulated 2-pyridones by selective intramolecular olefin hydroarylation. The switch between the exo- and endo-cyclization modes is controlled by two complementary sets of ligands. Irrespective of the ring size, the regioselectivity during the cyclization is under full catalyst control. Simple cyclooctadiene promotes an exo-selective cyclization, whereas a bulky N-heterocyclic carbene ligand results in an endo-selective mode. The method was further applied in the synthesis of the lupin alkaloid cytisine.CH activationcyclizationheterocyclesN-heterocyclic carbenesnickeltext::journal::journal article::research article