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. This ligand allows for mild reaction temperatures, and leads to the annulated pyridones in excellent yields and enantioselectivities.
An enantioselective nickel(0)-catalyzedC À Hf unctionalization 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.T he process is characterized by aclear endo-cyclization preference to yield the sought-after six-membered-ring products.K ey for the success of the activation and selectivity in the cyclization was the development of anovel chiral SIPr carbene ligand analogue with very bulky flanking groups.
C-H Functionalization has been established as an efficient way to generate molecular complexity. The formation of stereogenic carbon atoms by asymmetric C-H functionalization has seen tremendous progress over the last decade. More recently, the direct catalytic modification of C-H bonds has been powerfully applied to the formation of non-carbon stereogenic centers, which constitute a key design element of biologically active molecules and chiral ligands for asymmetric catalysis. This area was opened by a seminal report describing enantioselective C-H functionalization for the formation of a silicon stereocenter. It rapidly expanded with advances in the enantioselective formation of phosphorus(V) centers. Moreover, enantioselective routes to chiral sulfur atoms in the oxidation state IV (sulfoxides) and VI (sulfoximines) have been disclosed. Herein, we discuss methods of using selective functionalization of C-H bonds to generate a remote heteroatom stereogenic center via an inner-sphere C-H activation mechanism.
An enantioselective nickel(0)-catalyzedC À Hf unctionalization 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.T he process is characterized by aclear endo-cyclization preference to yield the sought-after six-membered-ring products.K ey for the success of the activation and selectivity in the cyclization was the development of anovel chiral SIPr carbene ligand analogue with very bulky flanking groups.
N-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. These chiral NHC ligands were applied in the nickel-catalyzed enantioselective C–H functionalization of N-heterocycles. Nickel-NHC catalysis unlocked the stereoselective
C–H annulation of 2- and 4-pyridones, delivering fused bicyclic compounds found in many biologically active compounds. Applying a bulky, yet flexible ligand scaffold enabled the highly enantioselective C–H functionalization of pyridones under mild conditions. The introduction of
a bulky chiral SIPr analogue enabled the nickel-catalyzed enantioselective C–H functionalization of indoles, yielding valuable tetrahydropyridoindoles. Additionally, pyrrolopyridines, pyrrolopyrimidines and pyrroles were efficiently functionalized, delivering chiral annulated azoles.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.