Iridium-Catalyzed Enantioselective C4-Alkylation of Indoles with α-Olefins and Styrenes

Indoles bearing a stereogenic center at the C4 position are key motifs in natural products and pharmaceuticals, yet their catalytic enantioselective synthesis remains a formidable challenge. Herein, we report an iridium-catalyzed enantioselective C4-alkylation of indoles with α-olefins and styrenes. The reaction proceeds with exclusive C4 selectivity and excellent enantioselectivity across a broad range of substrates. The C3 N, N -dibenzylamide directing group and the chiral spiro diphosphite ligand are essential for achieving high regio- and enantioselectivity. Density functional theory calculations elucidate the origins of regio- and enantioselectivity. This method provides a general atom- and step-economical route to chiral C4-alkylated indoles.