Ni(0)-Catalyzed Synthesis of Polycyclic α,β-Unsaturated γ-Lactams via Intramolecular Carbonylative Cycloaddition of Yne-imines with CO

A Ni(0)-catalyzed intramolecular carbonylative cycloaddition between 1,5-yne-imines and carbon monoxide (CO) is disclosed. When Ni(CO)(3)PCy(3)was employed as a pre-catalyst, a variety of polycyclic alpha,beta-unsaturated gamma-lactams were prepared in up to 78% yield with 100% atom efficiency. Aza-nickelacycles, generated by the oxidative cyclization of yne-imines on the Ni(0) center, were experimentally confirmed as key intermediates. Moreover, diastereoselective transformations of the obtained products to afford highly substituted polycyclic gamma-lactams with three contiguous carbon stereocenters are reported.

Automated summary

A Ni(0)-catalyzed intramolecular carbonylative cycloaddition between 1,5-yne-imines and carbon monoxide was explored in this study. By using Ni(CO)(3)PCy(3) as a pre-catalyst, various polycyclic alpha,beta-unsaturated gamma-lactams were efficiently synthesized, with a yield of up to 78% and 100% atom efficiency. Aza-nickelacycles were confirmed as key intermediates, and diastereoselective transformations of the products led to highly substituted polycyclic gamma-lactams with three contiguous carbon stereocenters.