Ni-Catalyzed direct iminoalkynylation of unactivated olefins with terminal alkynes: facile access to alkyne-labelled pyrrolines

Abstract

The direct iminoalkynylation of unactivated olefins with terminal alkynes is achieved for the first time by nickel-catalyzed cascade iminyl-radical cyclization/Sonogashira-type coupling of γ,δ-unsaturated oxime esters under mild conditions. This transformation...

The Alkynylative Difunctionalization of Alkenes

“…In 2021, Zhang reported the Ni‐catalyzed amino‐alkynylation of unactivated alkenes with terminal alkynes for the first time in the presence of K 3 PO 4 (Scheme 22). [60] The key feature of the protocol is the use of terminal alkynes as alkynylating reagents and the side reactions were avoided effectively that oligomerization and/or dimerization of terminal alkynes under the catalysis of a low‐valent metal [61,62] . Based on the results of the radical trap experiment and radical clock experiment, they also proposed a radical mechanism (Scheme 23).…”

Nickel-Catalyzed Reductive Iminoarylation of Oxime Ester-Tethered Alkenes: Rapid Entrance to Diverse Functionalized Pyrrolines

“…8 Moreover, it offers a rapid and modular protocol for the synthesis of pyrroline derivatives, which are inaccessible for obtaining by carboamination with nucleophilic amines. 9 Prior work from Bower, Zhu, Selander, and our group has demonstrated the good performance and high robustness of the umpolung method by palladium-or nickel-catalyzed coupling of unsaturated oxime esters with nucleophiles such as organoboron or tin compounds, 10 heteroarenes, 11 and terminal alkynes 12 metallic reagents and specific substrates limited its generalizability and practicability. On the contrary, reductive crosscoupling has emerged as a powerful and reliable tool in organic synthesis since the utilization of air-and moisture-sensitive organometallics is avoided.…”

“…16 The mass balance for this reaction was ascribed to the generation of some inevitable byproducts such as ketone (from imine hydrolysis) and hydrogenated pyrroline (from reductive cyclization). Ligand screening indicated that the tridentate nitrogen-based ligands (e.g., L1−L3), which gave the best results in our nickel-catalyzed alkynylation reactions, 12,15 were inferior for this transformation, while the bidentate ones (e.g., L4−L6) delivered superior performance; the relatively electron-rich L6 remained the optimal ligand (entries 2−6). Other nickel sources, including NiCl 2 (glyme), NiI 2 , and Ni(acac) 2 , were also effective precatalysts for this iminoarylation process, albeit with reduced yields (entries 7−9, respectively).…”

“…With our continued interest in developing novel transformations by nickel catalysis and recent work on iminoalkynylation of unsaturated oxime esters with terminal alkynes, herein, we disclose the first example of nickel-catalyzed iminoarylation of oxime ester-tethered alkenes with (hetero)­aryl halides via a reductive strategy (Scheme B). This transformation features mild conditions, a broad substrate scope, excellent functional group tolerance, and efficient late-stage modification of several drug derivatives.…”

Enantioselective Reductive N-Cyclization–Alkylation Reaction of Alkene-Tethered Oxime Esters and Alkyl Iodides by Nickel Catalysis

“…To further expand the scope of this chemistry from carbo- to heterocyclization, we wondered whether γ,δ-unsaturated oxime esters could cyclize and couple to alkyl halides enantioselectively. In addition to the enantioselectivity challenge noted above, such an effort will suffer from complicated chemoselectivity issues raised by the cross-electrophile reaction . To our knowledge, not even racemic aza-Heck cyclization and coupling with alkyl–X or alkyl–M is known.…”