The annulation of N -hydroxyoximes and 1,3-diyne to synthesize alkynylated isoquinolines regioselectively catalyzed by ruthenium: a theoretical study.

The mechanisms of the regioselective annulation of N -hydroxyoximes and 1,3-diyne to synthesize alkynylated isoquinolines by using the catalyst [RuCl 2 ( p -cymene)] 2 have been theoretically investigated with the aid of density functional theory (DFT) calculations. The role of the additive KPF 6 employed in this experiment is clarified based on our mechanistic studies. PF 6 - could displace one free Cl - to activate the proximal arene C-H bond via the achievable outer-sphere base-assisted concerted metalation/deprotonation mechanisms. It can be deduced that the 1,3-diyne migratory insertion mode plays a key role in controlling the regioselectivity. The origin of the regioselectivity is probed by investigating electronic effects. The stronger electron-donating effect of the phenyl group compared with the alkynyl group facilitates the generation of 4-alkynylated isoquinoline. The impact of substituent groups on the regioselectivity could also be attributed to the electronic effects. The high electron density of the proximal arene carbon and Ru atoms in the oxime moiety would restrict the formation of 4-alkynylated isoquinoline.