Asymmetric para-Functionalization of Anilines via Chiral Phosphoric Acid Catalysis: Access to CF₃-Substituted Indole–Aniline Quaternary Stereocenters

Parida, Chandrakanta; Granda, Jarosław M.

Asymmetric para-Functionalization of Anilines via Chiral Phosphoric Acid Catalysis: Access to CF₃-Substituted Indole–Aniline Quaternary Stereocenters

Abstract

We report a chiral phosphoric acid-mediated para-selective functionalization of diphenylamines with propargylic 3-methyleneindoles, enabling the construction of acyclic quaternary stereocenters bearing a trifluoromethyl substituent under mild conditions. This protocol delivers indole-aniline frameworks in good yields and excellent enantioselectivities (up to 99% ee) across 26 examples with broad tolerance to indole, alkyne, and aniline substitution. Late-stage modification of estrone and L-menthol derivatives and diversification to urea and triazole scaffolds underscore utility, expanding asymmetric para-functionalization of anilines.

Keywords

chiral phoshoric acids organocatalysis indole asymmetric synthesis diphenylamine

Citation

Parida, Chandrakanta, Granda, Jarosław 2025, "Asymmetric para-Functionalization of Anilines via Chiral Phosphoric Acid Catalysis: Access to CF₃-Substituted Indole–Aniline Quaternary Stereocenters". https://open.icm.edu.pl/handle/123456789/26255