Efficient Aerobic Oxidative Coupling of Methyl Heteroarenes with Indoles

• Published in: Chemistry : a European journal Vol. 29; no. 5; pp. e202202240 - n/a
• Main Authors: Zhang, Lei‐Yang, Wang, Nai‐Xing, Yan, Zhan, Wu, Yue‐Hua, Gao, Xue‐Wang, Feng, Ke, Lucan, Dumitra, Xing, Yalan
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 24.01.2023; Wiley Subscription Services, Inc
• Subjects: aerobic coupling reactions; C(sp3)−H; Catalysis; Chemistry; Chemistry, Multidisciplinary; Coupling; heteroarylacylation; Hydrogen bonds; Indoles; Indoles - chemistry; Intermediates; Ketones; Mass spectrometry; Mass spectroscopy; Oxidative Coupling; oxidative coupling reactions; Physical Sciences; Science & Technology; Substrates; FUNCTIONALIZATION; indoles; oxidative coupling reactions; C-H BOND; VINYLARENES; aerobic coupling reactions; C(sp)-H; heteroarylacylation; C(sp3)−H
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202202240

Direct oxidative coupling of inert C(sp3)−H bond has been a great challenge. Herein, an environmentally friendly aerobic oxidative coupling of α‐methyl substituted N‐heteroarenes with indoles is reported. A variety of diheteroaryl ketones were prepared in good yields (up to 72 %). This protocol features simple operation and broad substrates scope (26 examples). Significantly, a plausible mechanism about catalytic cycle was proposed, and two key intermediates were confirmed by high resolution mass spectrometry. A sustainable and environmentally friendly aerobic oxidative coupling of α‐methyl substituted N‐heteroarenes with indoles was first reported. A series of di‐heteroaryl ketones (26 examples) were obtained in moderate yields (up to 72 % yield), providing a highly atom‐economic approach for synthesizing complex pharmaceutical intermediates from small molecules. A plausible mechanism about cyclic catalysis was proposed and confirmed.