Highly Enantioselective Michael Addition of Cyclic Diketones to β,γ-Unsaturated α-Keto Esters Catalyzed by Squaramide Organocatalyst

A new tertiary amine-squaramide organocatalyst has been developed and applied to the asymmetric Michael addition of cyclic diketones to β,γ-unsaturated α-keto esters. The catalyst system performed well with a low catalyst loading of 1 mol% under mild reaction conditions. A series of synthetically and pharmaceutically useful chiral bicyclic compounds were obtained in high yields (up to 97%) with excellent enantioselectivities (up to 99 % ee). Furthermore, this catalytic system can be used efficiently in large-scale reactions with the yields and enantioselectivities being maintained.

Dearomative [4 + 3] cycloaddition of furans with vinyl-N-triftosylhydrazones by silver catalysis: stereoselective access to oxa-bridged seven-membered bicycles

The first example of dearomative [4 + 3] cycloaddition between furans and vinyl-N-sulfonylhydrazones as vinylcarbene precursors is reported. The merger of silver catalysis and easily decomposable vinyl-N-triftosylhydrazones enabled the efficient synthesis of a variety of skeletally and functionally diverse oxa-bridged seven-membered bicyclic compounds with complete and predictable stereoselectivity. The combination of experimental studies and DFT calculations disclosed that the silver-catalyzed reaction proceeds via a concerted [4 + 3] cycloaddition mechanism, rather than the generally accepted cyclopropanation / Cope rearrangement pathway by rhodium catalysis.

Ruthenium-catalyzed Asymmetric Dehydrative Allylic Cyclization of Chalcogen 5-Membered Heteroaromatics

The asymmetric dehydrative intramolecular allylation reactions of furan and thiophene were performed using a cationic cyclopentadienyl-ruthenium (CpRu) complex of a chiral pyridine carboxylic acid, namely Cl-Naph-PyCOOH. Both furan and thiophene tethered with an allylic alcohol gave the corresponding bicyclic compounds in high yields and enantioselectivities using 0.1–5 mol% of catalyst. The reaction was found to proceed via a similar enantioface selection method mechanism to that previously reported by our group, which involved halogen and hydrogen bond formation, in addition to the generation of an intermediate σ-allyl complex.

Synthesis of Nitrogen- and Oxygen-Containing Heterocycles by Prins Cyclization in Continuous Flow

Aza-silyl-Prins and oxa-Prins cyclization reactions in continuous-flow chemistry are described for the synthesis of the corresponding tetrahydropyridines and pyran derivatives, respectively. In particular, the use of pyridine-carboxaldehydes for aza-silyl-Prins reaction led to either a symmetrical triarylmethane or two new bicyclic compounds. 4-Fluorinated-2-substituted tetrahydropyran derivatives were also obtained in the oxa-Prins cyclization with good selectivity in favor of the anti-isomer.

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

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.