Organocatalytic Regio- and Enantioselective 1,8-Additions of Nitrogen and Sulfur Nucleophiles to 6-Methylene-6H-indoles

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 N-2 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.