The asymmetric Friedel–Crafts reaction is one of the most powerful methods to synthesize optically active aromatic compounds. Particularly, the Friedel–Crafts alkylation of arenes with unsaturated compounds activated by chiral Bronsted acids provides direct access to enantiopure aromatic derivatives with perfect atom economy. In this tutorial review, recent progress in the development of chiral Bronsted acid-catalyzed asymmetric Friedel–Crafts reactions is presented.

Chiral Bronsted acid catalyzed Friedel-Crafts alkylation reactions

Highly Enantioselective Friedel–Crafts Reaction of 4,7‐Dihydroindoles with Imines by Chiral Phosphoric Acids: Facile Access to 2‐Indolyl Methanamine Derivatives

Room Temperature Copper‐Catalyzed 2‐Functionalization of Pyrrole Rings by a Three‐Component Coupling Reaction

Synthesis of polysubstituted dihydropyridines by four-component reactions of aromatic aldehydes, malononitrile, arylamines, and acetylenedicarboxylate.

A highly efficient Friedel-Crafts reaction of 4,7-dihydroindoles with β,γ-unsaturated α-keto esters by a chiral N-triflyl phosphoramide was realized, affording the 2-substituted 4,7-dihydroindoles with up to 98% ee for a wide range of substrates. The Friedel-Crafts alkylation together with a subsequent oxidation of the product with p-benzoquinone led to a 2-alkylated indole derivative in 98% ee.

Highly Enantioselective Friedel–Crafts Reaction of 4,7‐Dihydroindoles with β,γ‐Unsaturated α‐Keto Esters by Chiral Brønsted Acids

Reaction of 4,7-dihydroindole and dimethyl acetylenedicarboxylate provided a convenient route to functionalized 2-vinylindoles. Diels-Alder reactions of the 2-vinylindoles with naphthoquinone, p-benzoquinone, 1,2-dicyano-4,5-dichloroquinone, N-phenyltriazolinedione, and tetracyanoethylene were investigated to give [c]annelated 1,2-dihydro, 1,2,3,4-tetrahydro, and fully aromatized carbazoles. The structure and formation mechanism of both 2-vinylindoles and their cycloadduct are discussed.

Synthesis of new 2-vinylation products of indole via a Michael-type addition reaction with dimethyl acetylenedicarboxylate and their Diels-Alder reactivity as precursors of new carbazoles.

Hiiseyin Cavdar

Papers

Synthesis of new 2-vinylation products of indole via a Michael-type addition reaction with dimethyl acetylenedicarboxylate and their Diels-Alder reactivity as precursors of new carbazoles.