Intermolecular dearomative C2-arylation of N-Ac indoles activated by FeCl₃

Abstract

We report the FeCl3-mediated direct addition of electron-rich arenes to the C2-position of electrophilic N-Ac indoles under mild conditions (room temperature, air). No functional group is required on the arene nucleophile: one of its C-H bonds is added to the C2[double bond, length as m-dash]C3 double bond of the indole nucleus in a Friedel-Crafts-type reaction. This dearomatisation process delivered a broad range of C2-arylated indolines.

Dearomatization Reactions of Indoles to Access 3D Indoline Structures

“…We learned that the regioselectivity was dependent of the substitution of the C3 position since exclusively 2-aryl-N-Ac indolines 19 were obtained (Scheme 6). 15 Simultaneously to this work, Nishina reported the same transformation with boron trifluoride etherate in hexafluoroisopropanol (HFIP) but probably with a distinct mechanism since in the case of a 3-substituted indole, the 2-aryl-indoline is also obtained in a modest yield instead of the 3-arylindoline of type 8. 16 We then gathered mechanistic insights of this general hydroarylation reaction which requires 2 equivalents of Fe-Cl 3 .…”

Triflic Acid as an Efficient Brønsted Acid Promoter for the Umpolung of N‐Ac Indoles in Hydroarylation Reactions

“…In particular the thiophene‐containing spirocyclic derivative 4 d was obtained in 97% yield with TfOH in 2 hours, compared to 27% with FeCl 3 . We recently established that if the N−Ac indole was unsubstituted at the C3‐position, the aryl nucleophile reacted at the C2‐position in presence of FeCl 3 . The same regioselectivity was observed with TfOH for the reaction with p ‐methyl anisole 2 a , leading to 5 a – c .…”

Iron(III) Chloride as a Mild Catalyst for the Dearomatizing Cyclization of N-Acylindoles

“…In the 2-substituted derivatives the phenyl (2q) or cyclohexyl units (2r) stick out vertical to this plane. The corresponding intermolecular reaction between 1x and 4methyl phenol 13 only proceeds with stoichiometric amounts of FeCl 3 and as described earlier 14 results in 15 % yield of the C-C coupling product 3 (Scheme 4,(a)). Cyclizations of the pyrrole 1y, benzimidazole 1z or amine derivative 1zb do not proceed.…”