Aerobic oxidation of tertiary amines

An aerobic oxidation of tertiary amines catalyzed by Cobalt Schiff-base complexes afforded N-oxides in high yields [120]. The reaction was run at room temperature with 0.5 mol% of the cobalt catalyst 35 (Eq. (8.28)). The presence of molecular sieves (5 enhanced the rate of the reaction. With this procedure, various pyridines were oxidized to their corresponding N-oxides in yields ranging from 50 to 85%. Electron-deficient pyridines such as 4-cyanopyridine gave a slow reaction with only 50% yield. 

The same author also reported on an aerobic oxidation of tertiary amines and pyridines to their corresponding N-oxides catalyzed by ruthenium trichloride [121]. 

Aerobic oxidation of tertiary amines to N-oxide on a heterogeneous gold catalyst (Au/C) was reported to give high yields and selectivity in aqueous solution [122]. 

Recently, a new type of reaction - that is, aerobic oxidative cyanation of tertiary amines - was discovered. In this reaction, oxidation with molecular oxygen in place of peroxides, in addition to direct carbon-carbon bond formation by trapping of the iminium ion intermediates with a carbon nucleophile under oxidative conditions, is accomplished simultaneously. The ruthenium-catalyzed oxidation of tertiary amines with molecular oxygen (1 atom) in the presence of sodium cyanide gives the corresponding a-aminonitriles (Eq. 3.74) [132], which are useful for synthesis of a-amino acids and 1,2-diamines. 

The aerobic flavin system with NHzNHzasa reducing agent that was employed for the sulfoxidation (Section 8.2.2.2) can also be used for the N-oxidation of tertiary amines [59]. However the reaction requires elevated temperature (60 °C) (Eq. (8.27)), most likely because elimination of O H from the flavin-OH (cf. 26 17, Scheme 8.4) is difficult for the N,N,N-3,5,10-trialkylated flavin at the higher pH caused by the amine. 

As a further extension, the Kim group very recently developed the aerobic oxidation and [l,5]-hydride transfer/cyclization sequence starting from readily available ortho tertiary amine substituted cinnamyl alcohols 24 (Scheme 4.12). The tetrapropylammonium perruthenate (TPAP) was identified as the competent catalyst for the initial aerobic oxidation of the allylic alcohols. The synthetically useful tetrahydroquinoline derivatives 25 were prepared in moderate yields and high level of enantioselectivity. 

Murahashi et al. [1] reported Ru(III)-catalyzed aerobic oxidative cyanation of N,N-dimethylanilines with NaCN in 2003, and the next year Li and co-workers developed an efficient Cu(I)-catalyzed alkynylation of tertiary amines with TBHP... 

Scheme 2.4 Cu-catalyzed aerobic oxidative aliyiation of tertiary amines and mechanistic studies [18]...

Scheme 2.5 Cu-catalyzed aerobic oxidative as3Tumetric olefination of tertiary amines [29]...

Recently, Kanai and co-workers developed a novel catalytic system for oxidation of benzyl amines and anilines to the corresponding imines with molecular ojg gen under mild conditions (Scheme 7.11). Inspired by Iwa-buchi s 2-azaadamantane-AI-03grl (AZADO) oxidation, they designed 9-azabi-cyclo[3.3.1]nonan-3-one AT-ojgrl (ketoABNO) as a more electron-deficient redox mediator and found that the combination with Cu(I) was effective for efficient aerobic oxidation of amines. Based on this result, they successfully applied their oxidation chemistry to CDC reactions. When the chiral Box ligand was used, an aerobic nitro-Mannich reaction between N-PMP glycine and 1-nitropropane proceeded with excellent diastereo- and enantioselectivity (20 1 diastereomeric ratio (dr) and 95% ee of the major syn isomer). In this case, EtgN was used as a co-catalyst to accelerate the addition reaction, because tertiary amines are inert to the ketoABNO/Cu(i) system. 

The dihydroxylation of olefins with an osmium catalyst also utilizes chiral tertiary amine ligands to achieve high yields and enantioselectivity. Soon after Krief and coworkers reported on the coupled 02/PhSeCH2Ph oxidation [34], Bel-ler and coworkers discovered a direct 02-coupled catalytic aerobic oxidation of olefins was possible using a phosphate-buffered pH 10.4 solution (Scheme 5.21) [69]. Under increased pressure with air rather than O2, the catalyst remains active and a TOP of 40 h is possible. This system does not quite achieve as high an enantioselectivity as the AD-Mix methods [70]. 

Several functional groups, including nitro, azo, tertiary amine N-oxide, aldehyde, ketone, sulfoxide, and alkyl polyhalide, are reduced by mammals in vivo. Toxic free radicals are often formed as intermediates during reduction. Although some of these reactions, or more accurately the initial sequence of the reactions, occur under aerobic conditions in vitro,... 

This combination of anaerobic and aerobic environment adds some complexity to the process but enables larger loads to be purified such as shown in Figure 2-23. One of the primary effluent gasses is trimethylamine. This tertiary amine has the very characteristic odor of rotten fish. Combustion methods can be used to treat this waste but these will produce NOj, effluents unless very special measures are employed in waste treatment. An alternative wet chemical processes was developed (Bohrer, 1999). The liquid solution waste can also be oxidized to produce a non-odoriferous solid using hydrogen peroxide. This alternative waste treatment process keeps the nitrogen fixed, reducing the atmospheric... 

On the other hand, novel photosensitizers were synthesized and applied in the visible-light-mediated oxidative hmctionalization of A-Aryl tetrahydroisoquinolines. A promising organogold complex was developed for aerobic oxidative C (sp )-H functionalization of secondary and tertiary amines (Scheme 3.5) [31]. Another feature of this novel gold complex was imderUned by production of... 

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