Endo -Selective Intramolecular Alkyne Hydroamidation Enabled by NiH Catalysis Incorporating Alkenylnickel Isomerization.

Intramolecular alkyne hydroamidation represents a straightforward approach for the access to synthetically valuable cyclic enamides. Despite some advances made in this realm, the ability to attain a precise regiocontrol still remains challenging, especially for endo cyclization that leads to six-membered and larger azacyclic rings. Herein, we report a NiH-catalyzed intramolecular hydroamidation of alkynyl dioxazolones that allows for an excellent endo selectivity, thus affording a range of six- to eight-membered endocyclic enamides with a broad scope. Mechanistic investigations revealed that Ni(I) catalysis is operative in the current system, proceeding via regioselective syn -hydronickelation, alkenylnickel E / Z isomerization, and Ni-centered inner-sphere nitrenoid transfer. In particular, the key alkenylnickel isomerization step, which previously lacked mechanistic understandings, was found to take place through the η 2 -vinyl transition state. The synthetic value of this protocol was demonstrated by diastereoselective modifications of the obtained endocyclic enamides to highly functionalized δ-lactam scaffolds.