Enantioselective Ni/N-Heterocyclic Carbene-Catalyzed Redox-Economical Coupling of Aldehydes, Alkynes, and Enones for Rapid Construction of Acyclic All-Carbon Quaternary Stereocenters.

Acyclic quaternary carbon stereocenters exist widely in natural products and bioactive molecules, but their enantioselective construction remains a prominent challenge. In particular, multicomponent enantioselective couplings of simple precursors to acyclic all-carbon quaternary stereocenters are very rare. We describe herein an N-heterocyclic carbene (NHC)-Ni catalyzed redox-economical three-component reaction of aldehydes, alkynes, and enones that proceeds in a highly chemo-, regio-, and enantioselective manner. A wide variety of valuable acyclic α-quaternary chiral ketones were synthesized in a single step with 100% atom economy. This reaction proceeds through the formation of a transient cyclic enolate followed by an aldol reaction/ring-opening sequence. The strategy is expected to inspire new and efficient approaches to generate other acyclic quaternary stereocenters.

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.