Catalytic enantioselective and site-specific Friedel–Crafts alkylation of 4-aminoindoles with β,γ-alkynyl-α-ketoimines for the synthesis of C7-functionalized indoles†

Abstract

Chiral phosphoric acid-catalyzed enantioselective Friedel–Crafts alkylation of 4-aminoindoles with β,γ-alkynyl-α-ketoimines has been developed. A range of optically pure C7-functionalized indoles bearing a quaternary α-amino acid or trifluoromethylated tetrasubstituted alkylamine motif were obtained with up to 98% yield and 99% ee. This protocol effectively incorporates site-specific Friedel–Crafts alkylation at the C7 site of 4-aminoindoles and regio-specific quaternary stereocenter construction at the α-position of β,γ-alkynyl-α-ketoimines, and opens a new avenue to access chiral C7-functionalized indoles.