Copper-Catalyzed Nitrogen Atom Transfer to Isoquinolines via C-N Triple Bond Cleavage and Three-Component Cyclization

A copper(I)-catalyzed tandem reaction of 2-bromoaryl ketones, terminal alkynes, and CH3CN is developed, which combines N atom transfer and three-component [3 + 2 + 1] cyclization, and efficiently produces densely functionalized isoquinolines in a facile, highly selective, and general manner. In the reaction, the formation of aromatic C-N bonds along with the complete C-N triple bond cleavage is first realized; Cu(III)-acetylide species might serve as the intermediates, which allow highly selective 6-endo-dig cyclization.

Automated summary

A copper(I)-catalyzed tandem reaction has been developed for the efficient synthesis of densely functionalized isoquinolines. This reaction combines N atom transfer and three-component cyclization, and demonstrates facile, highly selective, and general characteristics. The formation of aromatic C-N bonds and complete C-N triple bond cleavage are achieved in this reaction, possibly through the intermediates of Cu(III)-acetylide species enabling highly selective 6-endo-dig cyclization.