Iridium-Catalyzed Enantioselective C4-Alkylation of Indoles with α-Olefins and Styrenes
Kai Wang1, Kai-Yuan Tian1, Wen-Yao Wang1
1State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Frontiers Science Center for New Organic Matter, Nankai University, Tianjin 300071, China.
Abstract:
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.
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