Organocatalytic Regio- and Enantioselective 1,8-Additions of Nitrogen and Sulfur Nucleophiles to 6-Methylene-6<i>H</i>-indoles
Qianqian Song, Pei Zhang, Shuai Liang, Xuling Chen, Pengfei Li, Wenjun Li
Abstract
Remote stereocontrolled 1,8-addition of heteroatom nucleophiles to 6-methylene-6H-indoles generated in situ from 6-indolylmethanols has been developed for the first time. With the aid of a chiral phosphoric acid, 6-indolylmethanols reacted with benzotriazoles to furnish 1,8-adducts with a nitrogen-containing tertiary carbon stereocenter in 54–80% yield with 76–92% ee. Importantly, the stereoselective 1,8-addition of benzotriazoles featured N2 selectivity. Furthermore, using thioacids as nucleophiles enabled the formation of 1,8-adducts with a sulfur-containing tertiary carbon stereocenter in 70–78% yield with 75–94% ee.
Topics & Concepts
StereocenterChemistryNucleophileEnantioselective synthesisHeteroatomMethyleneAdductYield (engineering)Organic chemistrySulfurOrganocatalysisCarbon fibersSelectivityStereoselectivityMedicinal chemistryCatalysisRing (chemistry)MetallurgyMaterials scienceComposite materialComposite numberSynthesis of Indole DerivativesSulfur-Based Synthesis TechniquesChemical Synthesis and Reactions