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 η2-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.

Citation

Hoonchul Choi, Xiang Lyu, Dongwook Kim, Sangwon Seo, Sukbok Chang. Endo-Selective Intramolecular Alkyne Hydroamidation Enabled by NiH Catalysis Incorporating Alkenylnickel Isomerization. Journal of the American Chemical Society. 2022 Jun 08;144(22):10064-10074

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PMID: 35621341

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