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C 6 ‐Selective Direct Arylation of 2‐Phenylpyridine via an Activated N ‐methylpyridinium Salt: A Combined Experimental and Theoretical Study
Author(s) -
Yin Changzhen,
Zhong Kangbao,
Li Wenjing,
Yang Xiao,
Sun Rui,
Zhang Chunchun,
Zheng Xueli,
Yuan Maolin,
Li Ruixiang,
Lan Yu,
Fu Haiyan,
Chen Hua
Publication year - 2018
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201800666
Subject(s) - chemistry , catalysis , regioselectivity , reactivity (psychology) , ylide , iodide , carbenoid , medicinal chemistry , salt (chemistry) , density functional theory , combinatorial chemistry , inorganic chemistry , organic chemistry , rhodium , computational chemistry , medicine , alternative medicine , pathology
An elegant pre‐activation strategy, based on the formation of N ‐methylpyridinium iodide salts for C 6 ‐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, NMe 2 , 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.