Merging NiH Catalysis and Inner-Sphere Metal-Nitrenoid Transfer for Hydroamidation of Alkynes

Abstract

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.

Thioether-Directed NiH-Catalyzed Remote γ-C(sp3)–H Hydroamidation of Alkenes by 1,4,2-Dioxazol-5-ones

“…When 2,9-dibutyl-1,10-phenathroline ( L4 ) was utilized as the ligand, a highly γ selective methylene C­(sp 3 )–H amidation (up to 24:1 rr) was achieved in up to 90% yield (>40 examples). Recently, dioxazolones have emerged as versatile reagents for transition-metal-catalyzed hydroamidation . However, the use of dioxazolones in NiH-catalyzed alkene functionalization is less established.…”

Mechanism-Guided Development of Transition-Metal-Catalyzed C–N Bond-Forming Reactions Using Dioxazolones as the Versatile Amidating Source

“…A NiH-catalyzed strategy for the hydroamidation of alkynes with dioxazolones was developed by our group most recently, 75 which allowed convenient access to synthetically useful secondary enamides with either (E)-anti-Markovnikov or Markovnikov selectivity by the choice of bipyridine (bpy) ligands. In that study, H 2 O was found to be an essential component for high catalyst turnovers (Scheme 40).…”

NiH-Catalyzed Hydroamination/Cyclization Cascade: Rapid Access to Quinolines

“…Compared with the widespread success of CuH catalytic systems in alkene functionalization, NiH catalysis is more commonly used in the hydrofunctionalization of alkynes probably due to the slow protodemetalation of alkenylnickel intermediates . Recently, Chang and Seo achieved the first NiH-catalyzed hydroamidation of alkynes with dioxazolones for the selective synthesis of enamides . Given the intrinsic reactivity of NiH complexes, we recently questioned whether a NiH catalytic system could be applied to further expand the research on hydroamination of simple alkynes which is a long-standing challenge in Cu or Co catalytic systems.…”

“…These results strongly support that the expected hydroamination completely outcompetes the semireduction process in this NiH catalytic system. Compared with the easy protonation of well-established alkenylcopper intermediates, the protodemetalation of the alkenylnickel species is unfavorable because of the relatively high energy barrier …”