Asymmetric Friedel-Crafts Alkylation of Indoles: The Control of Enantio-and Regioselectivity

The asymmetric Friedel-Crafts reaction of indoles is a synthetic methodology that enables direct access to the enantiopure indole derivatives. In this review, work mainly carried out by You and his co-workers on the regio- and enantioselective synthesis of indole derivatives will be discussed. Chiral Bronsted acids or iridium complexes promote highly enantioselective Friedel-Crafts reactions of indoles and 4,7-dihydroindoles starting with various electrophilic reagents, such as imines, N-tosyl-substituted amines, beta,gamma-unsaturated a-keto esters, nitro-substituted olefins, aldehydes, and allyl carbonates. These methodologies can be used to readily prepare diverse enantioenriched indoles, such as indol-3-ylmethanamines, indol-2-ylmethanamines, unsymmetrical arylbis(indol-3-yl)methanes, 9-indol-3-ylfluorenes, tetrahydropyrano[3,4-b]indoles, tetrahydro-gamma-carbolines, and tetrahydro-beta-carbolines.