Regio- and Enantioselective C-H Cyclization of Pyridines with Alkenes Enabled by a Nickel/N-Heterocyclic Carbene Catalysis.

Annulated pyridines are ubiquitous scaffolds in many bioactive molecules. A highly regio- and enantioselective Ni(0)-catalyzed endo-selective C-H cyclization of pyridines with alkenes has been developed. An unprecedented enantioselective C-H activation at pyridyl 3- or 4-positions was enabled by bulky chiral N-heterocyclic carbene ligands. This protocol provides expedient access to a series of optically active 5,6,7,8-tetrahydroquinolines and 5,6,7,8-tetrahydroisoquinolines, compounds otherwise accessed with difficulty, in moderate to high yields (up to 99% yield) and enantioselectivities (up to 99% ee). To our knowledge, this is the first example of enantioselective C-H cyclization of pyridines to chiral annulated products.