Nickel-catalyzed Cycloaddition of Aromatic (O-Benzyl)ketoximes with Alkynes to Produce Isoquinoline and Isoquinoline N-Oxide Derivatives

Abstract

A nickel-catalyzed cycloaddition of aromatic (O-benzyl)ketoximes with alkynes to afford 3,4-disubstituted isoquinoline derivatives has been developed. The reaction involves oxidative addition of N–O bond of O-benzylketoxime to Ni(0) and subsequent intermolecular C–H bond activation via elimination of benzyl alcohol. It was also found that ketoximes participate in the nickel-catalyzed reaction with alkynes to furnish isoquinoline N-oxide derivatives.

Advancements in the Synthesis and Applications of Cationic N‐Heterocycles through Transition Metal‐Catalyzed C−H Activation

“…[52] The scope of the reaction was examined with al imited number of substrates to afford moderate yields of the two products (Scheme 8). [52] The scope of the reaction was examined with al imited number of substrates to afford moderate yields of the two products (Scheme 8).…”

“…In 2011, Kurahashi and Matsubara observed isoquinoline Noxide formation along with isoquinoline in the Ni 0 -catalyzed [4+ +2] cycloaddition of aromatic ketoximesa nd alkynes. [52] The scope of the reaction was examined with al imited number of substrates to afford moderate yields of the two products (Scheme 8). Later, Glorius et al developed an ovel methodf or the synthesis of isoquinoline N-oxides by the Rh III -catalyzed annulationr eaction of oximes and diazo compounds through CÀ Ha ctivation.…”

Manganese‐Catalyzed Dehydrogenative [4+2] Annulation of NH Imines and Alkynes by CH/NH Activation

“…Remarkably, the reaction produces H 2 as the predominant byproduct and eliminates the need for an oxidant. Though rhodium-, ruthenium-, palladium-, and nickel-catalyzed isoquinoline syntheses from imines (or its structural analogues) and alkynes by C À H activation have been reported, [8][9][10][11] an external or internal oxidant is generally needed in the reaction to induce catalytic turnover. In principle, the extrusion of H 2 is the most atom-economic, arguably ideal, and unprecedented feature among the reported annulations.…”

“…Various aromatic and aliphatic acetylenes reacted with 1 a readily to form the corresponding isoquinolines in high yields (3 ab-g, 3 ar, as). It is noteworthy that terminal alkynes, which are often challenging substrates for rhodium-, palladium-, nickel-, and ruthenium-catalyzed isoquinoline synthesis, [8][9][10][11]14] proved to be amenable to the current system. A broad range of terminal alkynes including aromatic (2 h-k), aliphatic (2 l,m), silylated (2 n), and heteroaromatic (2 o,p) alkynes, participated smoothly in the reaction to generate 3 ah-ao and 3 hp as single regioisomers in moderate to excellent yields.…”

High-Valent Co(III)- and Ni(II)-Catalyzed C–H Activation

“…A report of oximes directed C-H activation suggest that monodenate directing groups might also function of high-valent C-H activation; see:[99].…”