Qing-Feng Wu

Enantioselective Construction of Spiroindolenines by Ir-Catalyzed Allylic Alkylation Reactions

With 2-methyl-1,2,3,4-tetrahydroquinoline-derived phosphoramidite ligand (R,R(a))-L(6), Ir-catalyzed intramolecular C-3 allylic alkylation of indoles has been realized to afford highly enantioenriched spiroindolenine derivatives in 92-98% yields with up to >99/1 dr and 97% ee.

Enantioselective functionalization of indoles and pyrroles via an in situ-formed spiro intermediate.

Herein we report a highly enantioselective synthesis of polycyclic indoles and pyrroles with up to 99% ee by an iridium catalyst system consisting of a commercially available iridium precursor and a readily accessible ligand. Investigation of the reaction mechanism led to the discovery of an unprecedented dearomatized spiro intermediate and its in situ migration phenomenon. The new reaction mode features switching of the substituent from the indole C-3 position to the C-2 position (from the C-2 position to the C-3 position in the case of pyrrole) without loss of the enantiomeric purity, providing a novel concept in designing the asymmetric construction of enantiopure polycyclic indoles and pyrroles.

Asymmetric dearomatization of pyrrolesviaIr-catalyzed allylic substitution reaction: enantioselective synthesis of spiro-2H-pyrroles

Asymmetric dearomatization of pyrroles has been accomplished by using Ir-catalyzed intramolecular asymmetric allylic alkylation reactions. Reactions of allylic carbonate tethered pyrroles in the presence of [Ir(cod)Cl]2 and a BINOL-derived phosphoramidite ligand lead to efficient generation of spiro-2H-pyrrole derivatives with up to 96% ee.

Iridium-Catalyzed Intramolecular Asymmetric Allylic Dearomatization Reaction of Pyridines, Pyrazines, Quinolines, and Isoquinolines

The first Ir-catalyzed intramolecular asymmetric allylic dearomatization reaction of pyridines, pyrazines, quinolines, and isoquinolines has been developed. Enabled by in situ formed chiral Ir-catalyst, the dearomatized products were isolated in high levels of yield (up to 99% yield) and enantioselectivity (up to 99% ee). It is worth noting that the Me-THQphos ligand is much more efficient than other tested ligands for the dearomatization of pyrazines and certain quinolines. Mechanistic studies of the dearomatization reaction were carried out, and the results suggest the feasibility of an alternative process which features the formation of a quinolinium as the key intermediate. The mechanistic findings render this reaction a yet unknown type in the chemistry of Reissert-type reactions. In addition, the utility of this method was showcased by a large-scale reaction and formal synthesis of (+)-gephyrotoxin.

Direct Asymmetric Dearomatization of Pyridines and Pyrazines by Iridium‐Catalyzed Allylic Amination Reactions

The first iridium-catalyzed intramolecular asymmetric allylic dearomatization reaction of pyridines and pyrazines has been realized. 2,3-Dihydroindolizine and 6,7-dihydropyrrolo[1,2-a]pyrazine derivatives were obtained with excellent yields and enantioselectivity. This methodology features dearomatization by direct N-allylic alkylation of pyridines or pyrazines under mild reaction conditions.

Ruthenium-catalyzed intramolecular allylic dearomatization reaction of indole derivatives.

An efficient synthesis of spiroindolenine derivatives via a ruthenium-catalyzed intramolecular allylic dearomatization reaction has been developed. This method features a wide substrate scope, mild reaction conditions, and an operationally simple procedure.