Nickel-Catalyzed Regio- and Enantioselective Hydroarylation of 1,3-Dienes with Indoles

Abstract

The regio-and enantioselective functionalization of 1,3-dienes has become a powerful tool for the synthesis of allylic compounds, yet it remains a challenge for aliphatic dienes. Herein, we report a nickel-catalyzed asymmetric hydroarylation reaction of aliphatic and aromatic dienes with indoles to afford chiral indole derivatives. Because the reaction is performed under redox-neutral and mild conditions, various functional groups are tolerated in the reaction. Density functional theory calculations elucidate the mechanism of reaction and regio-and enantioselectivity of the nickel-catalyzed hydroarylation of aliphatic dienes with indoles. Keywordsnickel catalyst, aliphatic diene, asymmetric hydroarylation, chiral indole derivatives, C-C bond formation closely related to the electronic and steric nature of the diene substrate, and the use of cyclic and highly sterically hindered substrates is necessary for achieving good selectivities. 8,10,13 Therefore, a general method

Ni-Catalyzed Enantioselective Hydrofunctionalizations of 1,3-Dienes

“…Promising levels of enantioselectivity (77–84% ee ) and exquisite 1,2-regioselectivity were obtained using aryl-substituted linear dienes and a chiral spiro amino–phosphine ligand ( L9 ). In a following study, the Zhou laboratory established that nonprotected indoles were competent substrates for the selective hydro­(hetero)­arylation of 1,3-dienes (Figure B) . With the use of a chiral bisphosphine ligand ( L10 or L11 ) and diverse indole derivatives, excellent regio- and enantioselectivity were obtained for both aryl- and alkyl-substituted linear dienes over a range of ca.…”

Metal-catalyzed asymmetric heteroarylation of alkenes: diverse activation mechanisms

“…Very recently, Zhou et al also reported that nickel hydride catalysts promoted similar regio- and stereoselective addition of indoles to aliphatic 1,3-dienes. 111…”

Nickel-catalyzed hydroarylation reaction: a useful tool in organic synthesis

“…t BuOK in isopropanol at 60 °C for 72 h (Scheme 38). 59 The regio and enantioselectivity of the hydroarylation reaction was unaffected by the length and steric bulk of the diene's alkyl chain. Various functional groups such as olefins, ether, ester, and halide were also compatible in this reaction.…”