Divergent rhodium-catalyzed electrochemical vinylic C–H annulation of acrylamides with alkynes

• Published in: Nature communications Vol. 12; no. 1; pp. 930 - 9
• Main Authors: Xing, Yi-Kang, Chen, Xin-Ran, Yang, Qi-Liang, Zhang, Shuo-Qing, Guo, Hai-Ming, Hong, Xin, Mei, Tian-Sheng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.02.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 140/131; 140/58; 639/638/161/886; 639/638/549/933; 639/638/77/888; Alkynes; Biological activity; Catalysis; Chemical reactions; Divergence; Electrochemistry; Humanities and Social Sciences; multidisciplinary; Natural products; Organic chemistry; Oxidants; Oxidizing agents; Reaction mechanisms; Rhodium; Science; Science (multidisciplinary); Substrates; Transition metals
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-21190-8

α-Pyridones and α-pyrones are ubiquitous structural motifs found in natural products and biologically active small molecules. Here, we report an Rh-catalyzed electrochemical vinylic C–H annulation of acrylamides with alkynes, affording cyclic products in good to excellent yield. Divergent syntheses of α-pyridones and cyclic imidates are accomplished by employing N- phenyl acrylamides and N- tosyl acrylamides as substrates, respectively. Additionally, excellent regioselectivities are achieved when using unsymmetrical alkynes. This electrochemical process is environmentally benign compared to traditional transition metal-catalyzed C–H annulations because it avoids the use of stoichiometric metal oxidants. DFT calculations elucidated the reaction mechanism and origins of substituent-controlled chemoselectivity. The sequential C–H activation and alkyne insertion under rhodium catalysis leads to the seven-membered ring vinyl-rhodium intermediate. This intermediate undergoes either the classic neutral concerted reductive elimination to produce α-pyridones, or the ionic stepwise pathway to produce cyclic imidates. α-Pyridones and α-pyrones are ubiquitous structural motifs found in natural products and components of biologically active small molecules. Here, the authors report an oxidant-free Rh-catalyzed electrochemical divergent vinylic C–H annulation of acrylamides with alkynes to α-pyridones and cyclic imidates.