Chiral Phenol-2NO Ligand Cooperation with Achiral Organic Base in the Zn(II)-Catalyzed Asymmetric Alkylation Reaction of Indoles

The privileged C-2-symmetric rigid phenol-type ligand is more attractive but challenging in asymmetric catalysis. Herein, we designed and synthesized a class of rigid-featured chiral tridentate Phenol-2NO ligands, that incorporate the advantages of both the phenol skeleton and pyrroloimidazolone-based N-oxide moiety, from readily available L-prolinamides in operationally simple two steps and up to 44% overall yield. More importantly, using an achiral quinoline derivative as an additive, the newly developed Phenol-2NO ligand could serve as the anioic ligand upon deprotonative activation to coordinate to Zn(II) to form a highly enantioselective catalyst for the asymmetric Michael-type Friedel-Crafts alkylation reaction of indoles with 2,3-dioxopyrrolidines. Excellent yields (up to 90%) and high enantioselectivities (up to 99% ee) are obtained for a wide range of substrates under mild conditions. Experiments and DFT calculations revealed the reaction mechanism and the origins of the enantioselectivity. This also represented the first activation of phenol-type ligand/metal complex by an achiral organic base as the additive in asymmetric catalysis.