Environmentally Friendly Chemoselective Oxidation of Primary Aliphatic Amines by Using a Biomimetic Electrocatalytic System

Abstract

Environmentally friendly oxidation of primary aliphatic amines to imines has been successfully achieved, under metal-free conditions, by the use of diverse electrogenerated o-azaquinone mediators. High catalytic performance, together with high chemoselectivity, were observed with electron-poor o-azaquinone catalysts generated from 2-aminoresorcinol derivatives. Similar to copper amine oxidase enzymes, these mediators exhibited lower reactivity toward alpha-branched primary amines and no reactivity toward secondary amines. In the case of 3,4-aminophenol derivatives lacking a 2-hydroxy group, the generated o-azaquinone species failed to catalyze the oxidation of the amine to the corresponding imine. Further mechanistic considerations allowed a rationalization of the crucial role of the 2-hydroxy group in converting a catalytically inert species into a highly effective biomimetic catalyst.

A Metalloenzyme‐Like Catalytic System for the Chemoselective Oxidative Cross‐Coupling of Primary Amines to Imines under Ambient Conditions

“…Of particular note, only the reaction of 4‐methylbenzylamine 2 a with n ‐hexylamine 3 e (Table 2, entry 5) or aminomethylcyclohexane 3 f (Table 2, entry 6) revealed the simultaneous formation of homo‐ and cross‐coupled products ( 4 e or 4 f ) from the outset of the reaction, but with a preference for the homocoupled product 5 . These observations indicated that the homocoupled product was first generated as the sole imine product through the transamination mechanism reported earlier 14. 16 The homocoupled product was further alkylated by the second primary amine R′NH 2 through a transimination process19 to give the cross‐coupled product, the formation of which could be driven by continuous oxidation of the extruded primary amine RCH 2 NH 2 (self‐sorting step) as shown in Scheme .…”

“…The reaction progressed in all of the solvents used (entries 5–8). But, after 10 h, complete conversion was observed only in MeOH probably because strong solvation of the o ‐iminoquinone 1 ox by MeOH was required to enhance the electrophilicity of its quinonoid moiety, thereby favoring the nucleophilic attack of 4‐methylbenzylamine 2 a 14…”

“…We have ourselves described a biomimetic homogeneous catalytic system for the aerobic oxidation of primary amines to imines, based on the synergistic combination of copper and a topaquinone‐like organocatalyst 1 ox , first discovered from electrochemical investigations 14. Low catalyst loadings (2 mol % of 1 red precursor of 1 ox and 0.2 mol % of Cu I ) were sufficient to oxidize benzylic and aliphatic amines to self‐coupled imines under ambient conditions.…”

Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance

“…This one-pot procedure commences with the anodic dehydrogenation of a primary amine where an aminophenol is used as the mediator. 529–531 Electrochemical oxidation of the mediator furnishes an iminoquinone which can oxidize the amine through condensation and imine isomerization (Figure 34C, right column). The resulting N -aryl-imine can engage another primary amine, giving rise to an N -alkyl-imine.…”

Aerobic Oxidation of Amines to Imines by Cesium-Promoted Mesoporous Manganese Oxide

“…Aliphatic amines are relatively difficult to oxidize as mentioned in the previous studies 51 Along with symmetrical imine formation, the catalyst was also effective for the formation of asymmetrical imines. Depending on the molar ratio and nucleophilic properties of the partner amines, asymmetrical imines can be synthesized efficiently.…”