Work

meta ‐Methylation of Aniline and Anisole Derivatives via Palladium/S, O‐Ligand/Norbornene Cooperative Catalysis

Year: 2026

Type: article

Abstract: The introduction of methyl groups into drug candidates is a widely used strategy in medicinal chemistry to improve pharmaceutical properties. However, the introduction of methyl groups to the meta ‐position of electron‐rich arenes is a key challenge, since it is complementary to the natural reactivity in electrophilic aromatic substitutions and therefore mostly relies on prefunctionalized substrates or directing groups. Herein, we disclose a selective meta ‐CH methylation of anilines and anisole derivatives that eliminates the need for less step‐economical prefunctionalization strategies, enabled by a Pd/S, O‐ligand/norbornene cooperative catalytic system with the potential for modification and isotope labeling of drug candidates and natural products.

Source: ChemistryEurope

DOI: 10.1002/ceur.70299

Authors: Florian Papp, Verena Sukowski, Jos Verboom, Magnus J. Johansson, M. Ángeles Fernández‐Ibáñez

Institutions: University of Amsterdam, AstraZeneca (Sweden)

Language: English

Topic: Catalytic C–H Functionalization Methods

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: diamond

Funder: Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Awards: G4379530237, Navigating bias and inequality in the digital job market: Investigating annotated bias and impression management strategies in online profiles