Biomimetic Oxidative Deamination Catalysis via ortho-Naphthoquinone-Catalyzed Aerobic Oxidation Strategy

Abstract

An ortho-naphthoquinone-catalyzed oxidative deamination reaction has been developed where the molecular oxygen and water serve as the sole oxidant and nucleophile. The current aerobic deamination reaction proceeds via the ketimine formation between ortho-naphthoquinones and amines followed by the prototropic rearrangement and hydrolysis by water, representing a biomimetic oxidative deamination of amine species in the human body by the liver and kidneys. The compatibility of ortho-naphthoquinone organocatalysts with molecular oxygen and water opens up a new biomimetic catalyst system that can function as versatile deaminases for a variety of amine-containing molecules such as amino acids and DNA nuclear bases.

Catalytic Oxidative Deamination by Water with H2 Liberation

“… 33 More recently, a biomimetic oxidative deamination of benzylic amines was reported, which employs an ortho -naphthoquinone as the catalyst under aerobic conditions. 34 Compared to the enzymatic processes, traditional synthetic methods for the oxidative deamination of linear primary amines usually suffer from poor selectivity, affording a mixture of aldehydes, imines, and carboxylic acids ( Scheme 1 b). 35 , 36 Until now, all reported methods required the use of sacrificial oxidants, which can be problematic in being intolerant toward other oxidizable functionalities and generating waste.…”

One‐Pot Direct Oxidation of Primary Amines to Carboxylic Acids through Tandem ortho‐Naphthoquinone‐Catalyzed and TBHP‐Promoted Oxidation Sequence

“…The imine 2 and naphthol‐amine C are liberated from B , and the subsequent aerobic oxidation of C to the naphthol‐imine A requires molecular oxygen and another amine 1 , which results in the formation of H 2 O 2 and NH 3 . The involvement of intermediates A , B , and C has been verified in the mechanistic studies through HRMS‐ESI experiments [8] . Previously, the catalytic cycle of o ‐NQ 1 was facilitated in the presence of a catalytic amount of Cu(OAc) 2 , where the amounts of o ‐NQ 1 could be lowered to 2 mol % [16] .…”

“…The involvement of intermediates A, B, and C has been verified in the mechanistic studies through HRMS-ESI experiments. [8] Scheme 3. Control Experiments and Unseen TBHP Oxidation Capability.…”

Aerobic catalytic systems inspired by copper amine oxidases

“…The group of Luo [29] was the first to describe an effective ortho-quinone 10 as organocatalyst (10 mol%) which operates at room temperature, under one atmosphere of dioxygen without any metal cocatalyst (Scheme 6), showing the higher performance of ortho-quinone 10 vs. para-quinone 1 in the aerobic oxidation of alphabranched primary amines. Ortho-naphthoquinone 6 (10 mol%), described by Oh and co-workers for the oxidation of unbranched primary amines (Scheme 2), could also be used for the conversion of alpha-branched primary amines into imines [30]. However, whereas 10 promoted aerobic oxidation without any additives, the cooperative action of 6 and acetic acid (20 mol%), together with the dehydrating effect of 3 Å molecular sieves, was necessary for the interruption of the oxidation reaction at the ketimine stage.…”