General access to cubanes as benzene bioisosteres.

The replacement of benzene rings with sp-hybridized bioisosteres in drug candidates generally improves pharmacokinetic properties while retaining biological activity. Rigid, strained frameworks such as bicyclo[1.1.

Modular Chiral -Heterocyclic Carbene Ligands for the Nickel-Catalyzed Enantioselective C-H Functionalization of Heterocycles.

-Heterocyclic carbenes (NHCs) are the ligands of choice in a large variety of transformations entailing different transition metals. However, the number and variety of chiral NHCs suitable as stereo-controlling ligands in asymmetric catalysis remains limited. Herein we highlight the introduction of a modular NHC ligand family, consisting of a chiral version of the widely used IPr ligand.

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

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.

Nickel-Catalyzed Enantioselective Pyridone C-H Functionalizations Enabled by a Bulky N-Heterocyclic Carbene Ligand.

Annulated pyridones are an important scaffold found in many biologically active compounds. A Ni(0)-catalyzed C-H functionalization of 2- and 4-pyridones is disclosed, providing access to annulated pyridones via enantioselective intramolecular olefin hydroarylation. Key to the success of the transformation was the development of a sterically hindered and tunable N-heterocyclic carbene ligand resembling a chiral version of IPr.