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Organocatalytic Enantioselective Friedel–Crafts Aminoalkylation of Indoles in the Carbocyclic Ring

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journal contribution
posted on 21.03.2016, 00:00 by Marc Montesinos-Magraner, Carlos Vila, Alejandra Rendón-Patiño, Gonzalo Blay, Isabel Fernández, M. Carmen Muñoz, José R. Pedro
The first general catalytic method for the, so far elusive, enantioselective Friedel–Crafts functionalization of indoles in the carbocyclic ring is presented. This transformation contrasts with the usual tendency of these heterocycles to react at the azole ring. For this purpose, the four regioisomeric hydroxy carbocyclic-substituted indoles were reacted with several isatin-derived ketimines, using a Cinchona alkaloid-based squaramide, in a low 0.5–5 mol % catalyst loading, as a bifunctional catalyst. This methodology allows the functionalization of indoles in every position of the carbocyclic ring in a regio- and enantioselective fashion, by switching only the position of the hydroxy group in the starting material. Furthermore, several transformations were carried out, including the reductive elimination of the hydroxy group.