Mechanism Change of (+)-Nonlinear Effect in a Phase Separation System in a CuII-Catalyzed Asymmetric Friedel-Crafts Reaction Using a C2-Chiral Dioxolane-Containing-Bisamidine Ligand, Naph-diPIM-dioxo-iPr

Abstract

Abstract A CuII complex of bisamidine ligand LS, chirally modified naphtho[1,2-b:7,8-b′]dipyrroloimidazole (Naph-diPIM), catalyzes the enantioselective Friedel-Crafts (FC) reaction of indole (1a) with ethyl trifluoropyruvate (2) to give quantitatively the FC adduct 3a with a 98:2 S/R enantiomer ratio (er). The reaction shows no nonlinear effect (NLE) under the standard conditions of [1a] = [2] = 100 mM; [Cu(OTf)2] = [LS + LR] = 0.10 mM; CPME; and 0 °C irrespective of the catalyst aging temperature. A five-fold increase in the catalyst concentration (0.50 mM) changes the situation, leading to a strong (+)-NLE with phase separation of a white solid. The NLE is expressed by the Noyori-type mechanism: Aggregate of heterochiral dimer CuLSCuLR is separated from the reaction system (Khetero > 1 > Khomo). Furthermore, a strong (+)-NLE is observed via a purple solid liberation even with [CuII] = 0.10 mM after the catalyst aging at 100 °C in the presence of an excess amount of chiral ligand. A mechanistic study has revealed i) that the sterically disfavored homochiral 1:2 complex CuLSLS is more stabilized by an intramolecular n-π* interaction than the sterically favored heterochiral 1:2 complex CuLSLR and ii) that the (+)-NLE originates from the phase separation of heterochirally interacted (CuLSLSCuLRLR).