Tertiary amines enantioselective oxidation

Oxiranes may also be prepared by the cooxidation of aldehydes and olefins. There are two assumptions as regards the mechanism the oxidation occurs via either an acylperoxy radical or a peracid. The peracid oxidation is stereospecific. Experiments carried out with a view to assessing the radical versus nonradical mechanism indicate that the extent of the radical epoxidation depends on the structure of the olefin and the olefin/aldehyde ratio. Cooxidation in the presence of oxygen was achieved by irradiating the aldehyde and carrying out the reaction with the alkene after a suitable quantity of peracid had been obtained. Enantioselective epoxidation has been described in the reaction of (1-phenyl-alkylidene)malonitriles 63 catalyzed by optically active tertiary amines. ... 

The bulk of oxidations with tert-butyl hydroperoxide consists of epoxidations of alkenes in the presence of transition metals [147, 215, 216, 217, 218]. In this way, a,p-unsaturated aldehydes [219] and ketones [220] are selectively oxidized to epoxides without the involvement of the carbonyl function. Other applications of tert-butyl hydroperoxide such as the oxidation of lactams to imides [225], of tertiary amines to amine oxides [226, 227], of phosphites to phosphates [228], and of sulfides to sulfoxides [224] are rare. In the presence of a chiral compound, enantioselective epoxidations of alcohols are successfully accomplished with moderate to high enantiomeric excesses [221, 222, 223]. 

In the laboratory of F.G. West, the stereoselective silyl-directed [1,2]-Stevens rearrangement of ammonium ylides was investigated as a potential key step toward the enantioselective synthesis of various hydroxylated quinolizidines. The dimethylphenylsilyl group served as a surrogate for one of the hydroxyl groups in the product. The Fleming-Tamao oxidation was performed under Denmark s conditions to avoid oxidation of the tertiary amine to the corresponding A/-oxide, and the desired quinolizidine did was obtained in 81% yield. 

Recently, Chi and co-workers reported a highly enantioselective oxidative coupling reaction of aldehydes 14 with tertiary amines 13 under cooperative... 

The Wang group also realized enantioselective oxidative cross-coupling reactions between tertiary amines and the activated olefins by merging Cu(OTf)2 with quinine as the best cooperative catalysts/ A Morita-Baylis-Hillman-type mechanism is in operation. It was notable that molecular oxygen was employed as the sole oxidant. As shown in Scheme 2.12, the reactions between Ai-aryl THIQs and the a,p-unsaturated aldehydes or ketones 30 proceeded smoothly to afford the a-functionalized products 31 in up to 81% yield and 99% ee. 

Owing to the importance of optically active amino acid derivatives and the lack of successful systems for catalytic asymmetric CDC reactions of glycine derivatives with p-keto esters, Wang and co orkers embarked on the study of enantioselective CDC reactions of secondary and tertiary amines for the synthesis of optically active a-alkyl a-amino acids. In the presence of a catalytic amount of Cu(OTf)2 and BOX ligand L2 as the chiral catalyst, in combination with DDQ as the stoichiometric oxidant, the reactions of glycine esters 47 with a-substituted p-keto esters 48 underwent smoothly to afford the desired products 49 in satisfactory yields, moderate dr and excellent ee (Scheme 2.17). 

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. 

In the same year, Chi et al. developed an enantioselective oxidative coupling of tertiary amines with ahphatic aldehydes by combination of copper catalysis and aminocatalysis (Scheme 2.6) [31]. Both A -Aryl tetrohydroisoquinolines and simple A-Aryl tertiary amines can undergo this enantioselective alkylation reaction. Soon afterwards, organocatalytic enantioselective CDC reaction of ethers with aliphatic aldehydes [32] and Cu-catalyzed asymmetric CDC reaction of iV-carbamoyl tetrahydroisoquinohnes with terminal alkynes [33] were reported. 

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. 

Amine oxidases (AOs) can be used to synthesize primary, secondary and tertiary amines. Deracemization of chiral amines can be achieved by an enantioselective oxidation by an AO followed by a reduction using a nonselective reducing agent (Figure 7.12) [47d,76]. There are two types of AOs Type 1 (Cu/TOPA dependent, CAOs, EC.1.4.3.6) and Type 11 (Flavin dependent, EC 1.4.3.4). This chapter will solely focus on the flavin dependent monoamine oxidases. 

The catalytic asymmetric dihydroxylation reaction developed by Sharpless (Sharpless asymmetric dihydroxylation [SAD]) allows the straightforward oxidation of alkenes 76 to the corresponding cw-diols 77 with good to excellent yields and enantioselectivities without suffering from the presence of oxygen and moisture. The core of the catalytic system is based on an Os(VIII) metal center that coordinates the alkenes and transfers an oxygen atom to it using KsFe (CN)6 as terminal oxidant in the presence of enantiopure tertiary amines derived by dihydroquinidine 78 or... 

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]. 

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