Cooperative Cation-Binding Catalysis as an Efficient Approach for Enantioselective Friedel-Crafts Reaction of Indoles and Pyrrole

In this study, we demonstrated the cooperative cation-binding catalysis as an efficient approach for enantioselective Friedel-Crafts reaction of indoles and pyrroles. By using highly accessible chiral oligoethylene glycol (oligoEG) as the cation-binding catalyst and KF as the base, a highly enantioselective Friedel-Crafts reaction of indoles, 4,7-dihydroindoles, and pyrrole with bench-stable alpha-amidosulfones as in-situ equivalents of sensitive imines was achieved. The scope of this new catalytic protocol was not limited to aromatic imines. Heteroaromatic and aliphatic substrates as well as alpha-iminoethyl glyoxylate also afforded the desired products with excellent yields and ees. The enforced proximity of the catalyst and substrates in a chiral cage in situ formed by incorporation of the potassium salt enhanced the reactivity and efficiently transferred the stereochemical information, mimicking the action of enzymes.