C6‐Selective Direct Arylation of 2‐Phenylpyridine via an Activated N‐methylpyridinium Salt: A Combined Experimental and Theoretical Study. Issue 20 (4th September 2018)

• Record Type: Journal Article
• Authors: Yin, Changzhen; Zhong, Kangbao; Li, Wenjing; Yang, Xiao; Sun, Rui; Zhang, Chunchun; Zheng, Xueli; Yuan, Maolin; Li, Ruixiang; Lan, Yu; Fu, Haiyan; Chen, Hua
• Is Part Of: Advanced synthesis & catalysis. Volume 360:Issue 20(2018)
• Page Start: 3990
• Page End: 3998
• Publication Date: 2018-09-04
• Subjects: N-methylpyridinium -- C−H arylation -- Palladium -- Copper -- DFT; Catalysis -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Chemistry -- Periodicals; Chemistry, Technical -- Periodicals; Chemistry -- Periodicals; Catalysis -- Periodicals; Technology, Pharmaceutical -- Periodicals; 547.2
• DOI: 10.1002/adsc.201800666
• Languages: English
• ISSNs: 1615-4150

Abstract

Abstract: An elegant pre‐activation strategy, based on the formation of N ‐methylpyridinium iodide salts for C6 ‐selective direct arylation of 2‐phenylpyridines using Pd/Cu cooperative catalysis, has been developed. By this methodology, a wide range of unsymmetrical 2, 6‐diarylpyridines were synthesized with high reactivity and regioselectivity as well as good functional group tolerance. In particular, challenging substrates bearing electron donating groups (EDGs), such as OMe, NMe2, were also successfully employed in this reaction. Deuterium incorporation studies revealed that the C−H bond acidity is improved significantly in N ‐methylpyridinium salts compared with their N ‐Oxide and N ‐iminopyridinium ylide counterparts, thus solving the long‐standing problem associated with previous strategies for the synthesis of diaryl pyridines. Finally, the control experiments and DFT calculations supported a Pd‐catalyzed and Cu‐mediated mechanism in which a carbenoid copper species that is formed in‐situ from N ‐methylpyridinium salts, participates in a Pd‐catalyzed arylation followed by an iodide‐promoted N ‐demethylation process. Abstract :