Synthesis of Densely Substituted Pyridine Derivatives from 1-Methyl-1,3-(ar)enynes and Nitriles by a Formal [4+2] Cycloaddition Reaction

Authors：He, Dandan; Wang, Bowen; Duan, Kanghui; Zhou, Yang; Li, Meng; Jiang, Huanfeng; Wu, Wanqing^*

Source：Organic Letters, 2022, 24(6): 1292-1297.

DOI：10.1021/acs.orglett.1c04192

• H BOND ADDITION
• ISOQUINOLINES
• ACTIVATION
• COMPLEXES
• CATALYSIS
• AMIDE

An attractive method for assembling densely substituted pyridine derivatives from 1-methyl-1,3-(ar)enynes and nitriles via a formal [4+2] cycloaddition has been established. The well-balanced affinities of two alkali metal salts enable C(sp(3))-H bond activation and excellent chemo-and regioselectivities. Experimental studies revealed that nitrile functions only as a partial nitrogen source for pyridine synthesis, and the addition of a metalated imine intermediate to an intramolecular alkyne is the rate-limiting step.