Enantioselective Friedel-Crafts Alkylation Reactions of 3-Substituted Indoles with Electron-Deficient Alkenes.

Highly enantioselective Friedel-Crafts C2-alkylation reactions of 3-substituted indoles with α,ß-unsaturated esters and nitroalkenes were developed using chiral Lewis acids as catalysts, which afforded chiral indole derivatives bearing C2-benzylic stereogenic centers in good to excellent yields (up to 99%) and enantioselectivities (up to 96% ee).

Asymmetric Friedel-Crafts alkylation of α-substituted ß-nitroacrylates: access to ß(2,2)-amino acids bearing indolic all-carbon quaternary stereocenters.

A highly enantioselective Friedel-Crafts alkylation reaction of indoles with acyclic α-substituted ß-nitroacrylates is developed under the catalysis of Ni(ClO4)2-bisoxazoline complex at 1 mol % catalyst loading, affording chiral indolic ß-nitroesters bearing all-carbon quaternary stereocenters in excellent yields and ees of up to 97%. Transformation of one of the products to ß(2,2)-amino ester and tetrahydro-ß-carboline through nitro reduction and sequential Pictet-Spengler cyclization was exemplified.