The formal hydroamination/hydroamidation utilizing metal hydride is an appealing synthetic tool for the construction of valuable nitrogen-containing compounds from unsaturated hydrocarbons. While significant advances have been made for the functionalizations of alkenes in this realm, the direct hydroamidation of alkynes remains rather limited due to the high feasibility of the key metal-alkenyl intermediate to choose other reaction pathways. Herein, we report a NiH-catalyzed strategy for the hydroamidation of alkynes with dioxazolones, which allows convenient access to synthetically useful secondary enamides in (E)-anti-Markovnikov or Markovnikov selectivity. The reaction is viable for both terminal and internal alkynes and is also tolerant with a range of subtle functional groups. With H 2 O found as an essential component for high catalyst turnovers, the involvement of inner-sphere nitrenoid transfer is proposed that outcompetes an undesired semireduction process, thus representing the first example to show the competence of Ni catalysis for metal-nitrenoid formation from dioxazolones.

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.

Synthetic methods for constructing enantioenriched β-lactams are highly valuable given the ubiquity of this privileged heterocyclic unit in bioactive compounds, most notably in antibiotics such as penicillins and carbapenems. Intramolecular hydroamidation of β,γ-unsaturated amides would provide a convenient means to reach this alluring chemical space, yet it remains limited due to the regioselectivity issue arising from the difficulty associated with the formation of strained four-membered rings. Here we describe a NiH-catalysed strategy that addresses this challenge through the use of readily accessible alkenyl dioxazolone derivatives. The reaction transcends the conventional NiH operation mode via an unprecedented mechanism initiated by N-activation, thus allowing for proximal C–N bond formation with excellent regioselectivity, regardless of the electronic properties of substituents. This mechanistic platform is also highly effective for the enantioselective intramolecular hydroamidation of alkenes, which represents the first example of such a type of processes that enables the access to enantioenriched β-lactams.