Asymmetric Friedel−Crafts reaction of unsaturated carbonyl-tethered heteroarenes via vinylogous activation of Pd0-π-Lewis base catalysis

Abstract

The alkyne group can undergo facile transformations under palladium catalysis, such as hydropalladation, Wacker reaction, etc. Here we demonstrate that a chiral Pd⁰ complex can chemoselectively dihapto-coordinate to the alkyne moiety of 2-indolyl propiolates, and raise the Highest Occupied Molecular Orbital (HOMO)-energy ofthe deactivated heteroarenes via π-Lewis base catalysis. As a result, asymmetric C3-selective Friedel−Crafts addition to activated alkenes occurs, finally affording [3 + 2] or [3 + 4] annulation products with high enantioselectivity and exclusive E-selectivity. Moreover, this π-Lewis base vinylogous HOMO-activation strategy can be extended to remote Friedel−Crafts reaction of diverse five-membered heteroarenes tethered to a 2-enone or 2-acrylate motif with imines or 1-azadienes, and excellent enantiocontrol is generally achieved for the multifunctional adducts, which can be effectively converted to diverse frameworks with higher molecular complexity. In addition, NMR and density functional theory calculation studies are conducted to elucidate the catalytic mechanism.