Premium
Ligand‐Controlled Regiodivergent Nickel‐Catalyzed Annulation of Pyridones
Author(s) -
Donets Pavel A.,
Cramer Nicolai
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201409669
Subject(s) - quinolizidine , indolizidine , chemistry , intramolecular force , stereochemistry , annulation , regioselectivity , hydroamination , catalysis , ligand (biochemistry) , olefin fiber , combinatorial chemistry , enantioselective synthesis , alkaloid , organic chemistry , receptor , biochemistry
The 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.