Unbiased C3‐Electrophilic Indoles: Triflic Acid Mediated C3‐Regioselective Hydroarylation of N−H Indoles. (2nd June 2022)

• Record Type: Journal Article
• Authors: Sabat, Nazarii; Zhou, Weiping; Gandon, Vincent; Guinchard, Xavier; Vincent, Guillaume
• Is Part Of: Angewandte Chemie. Volume 134:Number 30(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-02
• Subjects: Dearomatization -- Indoles -- Indolines -- Super Acids -- Umpolung; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202204400
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: The direct dearomative addition of arenes to the C3 position of unprotected indoles is reported under operationally simple conditions, using triflic acid at room temperature. The present regioselective hydroarylation is a straightforward manner to generate an electrophilic indole at the C3 position from unbiased indoles in sharp contrast to previous strategies. This atom‐economical method delivers biologically relevant 3‐arylindolines and 3, 3‐spiroindolines in high yields and regioselectivities from both intra‐ and intermolecular processes. DFT computations suggest the stabilization of cationic or dicationic intermediates with H‐bonded (TfOH) n clusters. Abstract : Direct dearomative C3‐functionalization of indoles provided access to privileged scaffolds by an umpolung strategy. Against all odds, C3‐indolium intermediates could be generated from NH‐indoles under operationally simple conditions with triflic acid at room temperature to promote intra‐ and intermolecular C3‐regioselective hydroarylation. DFT studies suggest that these cationic or dicationic intermediates could be stabilized by H‐bonded clusters.