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

Abstract

The first general catalytic method for the, so far elusive, enantioselective Friedel−Crafts functionalization of
\nindoles in the carbocyclic ring is presented. This transformation contrasts with the usual tendency of these heterocycles to react
\nat the azole ring. For this purpose, the four regioisomeric hydroxy carbocyclic-substituted indoles were reacted with several isatinderived
\nketimines, using a Cinchona alkaloid-based squaramide, in a low 0.5−5 mol % catalyst loading, as a bifunctional catalyst.
\nThis methodology allows the functionalization of indoles in every position of the carbocyclic ring in a regio- and enantioselective
\nfashion, by switching only the position of the hydroxy group in the starting material. Furthermore, several transformations were
\ncarried out, including the reductive elimination of the hydroxy group.