Efficient Access to Isoquinolines via Rhodium-Catalyzed Oxidative Annulation of Pyridyl C-H Bonds Directed by Carbonyl with Internal Alkynes

An efficient synthesis of amino-substituted isoquinolines via Rh(III)-catalyzed oxidative [2+2+2] annulation of pyridines with alkynes has been developed, which is cooperatively enabled by a directing carbonyl and steric hindrance adjacent to the amino group of the pyridine, via a six-membered rhodacyclic intermediate without coordination with the pyridinic nitrogen. The establishment of this C-H activation strategy also paves the way for other oxidative transformations of heterocyclic C-H bonds.

Automated summary

An efficient synthesis of amino-substituted isoquinolines was achieved through Rh(III)-catalyzed oxidative [2+2+2] annulation, which was cooperatively enabled by a directing carbonyl and steric hindrance adjacent to the amino group of the pyridine. This C-H activation strategy also opens up possibilities for other oxidative transformations of heterocyclic C-H bonds.