Cobalt‐Catalyzed Electrophilic Amination of Aryl‐ and Heteroarylzinc Pivalates with N‐Hydroxylamine Benzoates

• Published in: Angewandte Chemie International Edition Vol. 57; no. 4; pp. 1108 - 1111
• Main Authors: Chen, Yi‐Hung, Graßl, Simon, Knochel, Paul
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 22.01.2018; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Amination; Amines; Aromatic compounds; Benzoates; Benzoic acid; Chemistry; Chemistry, Multidisciplinary; Cobalt; cobalt catalysis; cross-coupling; electrophilic amination; Hydroxylamine; organozinc pivalates; Physical Sciences; Science & Technology; Tuberculosis; ENHANCED AIR; PALLADIUM; tuberculosis; ARENES; COPPER; organozinc pivalates; electrophilic amination; CENTER-DOT-LICL; SENSITIVE AROMATICS; NUCLEOPHILES; ZINC REAGENTS; HETEROARENES; cross-coupling; cobalt catalysis; CARBON-NITROGEN BONDS
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201710931

Aryl‐ and heteroarylzinc pivalates can be aminated with O‐benzoylhydroxylamines at 25 °C within 2–4 h in the presence of 2.5–5.0 % CoCl2⋅2 LiCl to furnish the corresponding tertiary arylated or heteroarylated amines in good yields. This electrophilic amination also provides access to diarylamines and aryl(heteroaryl)amines. A new tuberculosis drug candidate (Q203) was prepared in six steps and 56 % overall yield by using this cobalt‐catalyzed amination as the key step. Animating aminations: A range of aryl‐ and heteroarylzinc pivalates underwent cobalt‐catalyzed electrophilic aminations with O‐benzoylhydroxylamines in good yields under mild conditions. This reaction can be applied to prepare arylamines and diarylamines. A new tuberculosis drug candidate was prepared in six steps and 56 % overall yield by using the cobalt‐catalyzed amination as the key step.