Work

Development of a Ligand for Cu-Catalyzed Amination of Base-Sensitive (Hetero)aryl Chlorides

Year: 2025

Type: article

Abstract: We report a new N 1, N 2 -diarylbenzene-1,2-diamine ligand, L6, that supports a copper catalyst capable of coupling base-sensitive aryl chlorides and amines that were previously unsuccessful substrates for Cu-catalyzed C–N coupling. A detailed structure–activity relationship study, combined with density functional theory (DFT) calculations, was used to uncover two key structural features that contribute to the efficacy of the catalyst derived from L6 . First, steric repulsion caused by a methyl substituent induces a conformational change that opens up additional space for ligand deprotonation and oxidative addition. Second, the trifluoromethyl groups create electrostatic interactions between the ligand and aryl chloride substrates that facilitate oxidative addition via through-space ligand–substrate interaction.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.5c10910

Authors: Han-Jun Ai, Binh Khanh Mai, Cecilia Liu, Peng Liu, Stephen L. Buchwald

Institutions: Massachusetts Institute of Technology, University of Pittsburgh

Language: English

Topic: Catalytic Cross-Coupling Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Awards: G1309160875, Metal-Catalyzed Methods for Organic Synthesis