Regioselective hydroarylation reactions of C3 electrophilic N-acetylindoles activated by FeCl3: an entry to 3-(hetero)arylindolines.
A method for the direct and rare umpolung of the 3 position of indoles is reported. The activation of N-acetylindole with iron(III) chloride allows the C-H addition of aromatic and heteroaromatic substrates to the C2=C3 double bond of the indole nucleus to generate a quaternary center at C3 and leads regioselectively to 3-arylindolines. Optimization, scope (50 examples), practicability (gram scale, air atmosphere, room temperature), and mechanistic insights of this process are presented. Synthetic transformations of the indoline products into drug-like compounds are also described.
Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), Equipe Méthodologie, Synthèse et Molécules Thérapeutiques, Univ Paris Sud and CNRS, 15 rue Georges Clemenceau, Bat 410, 91406, Orsay (France), Fax: (+33) 1-69-15-46-79.
Rodolphe
R
Beaud
Régis
R
Guillot
Cyrille
C
Kouklovsky
Guillaume
G
Vincent
CH activation; electrophiles; heterocycles; indoles; iron