Ligand-Enabled meta-Selective C–H Arylation of Nosyl-Protected Phenethylamines, Benzylamines, and 2‑Aryl Anilines

• Published in: Journal of the American Chemical Society Vol. 139; no. 1; pp. 417 - 425
• Main Authors: Ding, Qiuping, Ye, Shengqing, Cheng, Guolin, Wang, Peng, Farmer, Marcus E, Yu, Jin-Quan
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 11.01.2017; Amer Chemical Soc
• Subjects: Aniline Compounds - chemistry; Benzylamines - chemistry; bromides; Chemistry; Chemistry, Multidisciplinary; iodides; Ligands; Molecular Structure; palladium; phenethylamines; Phenethylamines - chemistry; Physical Sciences; pyridines; Science & Technology; standard operating procedures; AROMATIC FUNCTIONALIZATION; C(SP)-H BONDS; PALLADIUM; CATALYSIS; ACTIVATION; NORBORNENE; NITROGEN-HETEROCYCLES; ALKYLATION; ARENES; ALIPHATIC-AMINES
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.6b11097

A Pd-catalyzed, meta-selective C–H arylation of nosyl-protected phenethylamines and benzylamines is disclosed using a combination of norbornene and pyridine-based ligands. Subjecting nosyl protected 2-aryl anilines to this protocol led to meta-C–H arylation at the remote aryl ring. A diverse range of aryl iodides are tolerated in this reaction, along with select heteroaryl iodides. Select aryl bromides bearing ortho-coordinating groups can also be utilized as effective coupling partners in this reaction. The use of pyridine ligands has allowed the palladium loading to be reduced to 2.5 mol %. Furthermore, a catalytic amount of 2-norbornene (20 mol %) to mediate this meta-C–H activation process is demonstrated for the first time. Utilization of a common protecting group as the directing group for meta-C–H activation of amines is an important feature of this reaction in terms of practical applications.