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

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.