A Bioinspired Organocatalytic Cascade for the Selective Oxidation of Amines under Air

Abstract

A bioinspired organocatalytic cascade reaction for the selective aerobic oxidative cross-coupling of primary amines to imines is described. This approach takes advantages of commercially available pyrogallol monomeric precursor to deliver low loadings of natural purpurogallin in situ, under air. This is further engaged in a catalytic process with the amine substrate affording, under single turnover, the active biomimetic quinonoid organocatalyst and the homocoupled imine intermediate, which is then converted into cross-coupled imine after dynamic transimination. This organocatalytic cascade inspired by both purpurogallin biosynthesis and copper amine oxidases allows the aerobic oxidation of non-activated primary amines that non-enzymatic organocatalysts were not able to accomplish alone.

Recent Advances in the Synthesis of Benzimidazole Derivatives from the Oxidative Coupling of Primary Amines

“…45 Based on this insight, we have developed a double biomimetic reaction pathway resulting in the formation of 1,2-disubstituted benzimidazoles. 46 The reaction sequence starts from inexpensive commercially available pyrogallol and allows, under ambient air, the in situ generation of not easily accessible natural purpurogallin, which is further engaged in the transamination process analogous to that reported in Scheme 16, for producing, under single turnover, the active biomimetic organocatalyst IMQ′ (Scheme 17). Dynamic transimination followed by intramolecular cyclization and subsequent oxidation reactions produced the 1,2-disubstituted benzimidazole derivatives.…”

Pyrazine Radical Cations as a Catalyst for the Aerobic Oxidation of Amines

“…Imines are an important class of compounds with ample use in pharmaceutical and chemical industry, as they are key precursors for many biologically active heterocycles . Many of the reported procedures for oxidative cross‐coupling and homocoupling of amines use noble‐metal catalysts such as Co, Au, Pd, Ru, and V . Recently, many research groups focused on less expensive non‐noble catalysts, including Cu, Fe, Al,[21d], and others .…”

“…However, traces of heavy metals in the final product still represent a major issue. [21d], [21e], Due to this fact, metal‐free catalytic procedures gained much attention in the last years. It has been shown that graphite oxide and doped porous carbon[8b], are also suitable catalysts for amine oxidation.…”

“…Other approaches for amine oxidation involve also peroxides, TEMPO radicals, and other organocatalysts. [21e], [31b], However, some of these methodologies require either solid‐state catalysts (of complex preparation) or strong, sometimes hazardous, oxidants. Hence, the search for alternate mild metal‐free aerobic oxidation processes is still of high interest.…”

Redox‐Active Guanidines in Proton‐Coupled Electron‐Transfer Reactions: Real Alternatives to Benzoquinones?

“…[15][16][17] Moreover,l ow-potential o-quinone-type catalysts were recently shownt oe nablem anifold (bioinspired) aerobic oxidations. [18][19][20][21][22][23][24][25][26] Despite of the outstandings uccesss tory of quinones, some drawbacks oppose their large-scale applications.H ence cyanoor halo-substituted benzoquinones like CA are highly toxic, as they induce reactiveo xygen speciesa nd oxidative stress, showinga ni nflammatory response both in vivo and in vitro. [27] Moreover,the recycling of the quinones is sometimesproblematic due to side reactions.…”