Aldehydes hydroxyamination

Method B (catalysed by polymer-supported chiral fl-hydroxyamines) The aldehyde (1 mmol) is added to the polymer-supported catalyst (0.298 g) in n-C6Hu (2 ml) at 0°C and the mixture is stirred for 15 min. The dialkylzinc (1M in rt-C6H 4, 2.2 ml) is added and the mixture is stirred for 1-8 days at 0°C. The reaction is quenched with aqueous HCI (1M, 5 ml) and the mixture is filtered and extracted with CH2C12 (3x10 ml). The dried (Na2S04) extracts are evaporated to yield the chiral secondary alcohol. 

Low-valent niobium and tantalum react with imines to give the corresponding imine-niobium or -tantalum complexes. Some of these are isolated, and structures of the complexes are confirmed by X-ray analyses. These imine complexes react with aldehydes to give /3-hydroxyamines in good to excellent yields (Equation... 

Substituted imidazole 1-oxides 228 can be prepared by N-oxidation of imidazoles 248, by N-alkylation of 1-hydroxyimidazoles 249, or by cycliza-tion using suitable starting materials derived from a 1,2-dicarbonyl compound, an aldehyde, an amine, and hydroxyamine. The substituents at the three first starting materials are transferred to the product and make control over the substituents in the imidazole 1-oxide 228 possible depending on the protocol used by the synthesis. The synthesis of 3-hydroxyimidazole 1-oxides is presented in Section 3.1.6. 

Starting from aldehydes, which are converted into cyanohydrins whose hydroxyl group is protected as an acetal, one can also obtain a-hydroxyaldehydes by reaction with Red-Al or a-hydroxyamines via reduction by LAH [SBl] (Figure 4.9). 

The hydroxyamine (f) readily loses NH3 on the heating to give the aldehyde. This sequence achieves the removal of Cl from an aldose to form a new aldose with one less carbon, just like the Wohl and Ruff degradations. 

In other reactions that proceed via an acyliminium ion, O-vinyl iV,0-acetals rearrange smoothly to /3-(A-acylainino)aldehydes at 0 °C in CH2CI2 in the presence of TMSOTf with moderate to high diastereoselectivities (eq 78). However, TMSOTf failed to promote aprotic alk)fne-iminium cyclizations, which are readily enhanced by TMSCl, TMSBr, or SiCU. On the other hand, TMSOTf assists in the addition of enols to heteroaromatic imines or hydroxyaminal intermediates. ... 

Proline-derived tetrazole 5a was used for the reaction of nitrosobenzene with a-branched aldehydes. Selective formation of an a-hydroxyamination product over an a-amino>ylation product was observed by Kim and Park. Remarkably, N- vs. O- addition selectivity was observed for a,a-disubstituted aldehydes however, the enantioselectivities were only moderate (Scheme 9.45). 

The synthesis of (-)-A -acetyl-O-methylacosamine, " an amino sugar, is an interesting application of the process of cis-hydroxyamination catalyzed by palladium complexes of olefins developed by Trost and Sudhakar. Enantiomerically pure aldehyde 263 was first transformed to vinyl epoxide 264. The latter reacted smoothly with p-toluene sulfonyliso-cyanate in the presence of 1-3 mol% of palladium and 6-18 mol% of tiiisopropyl phosphite in THF at room temperature. As thermal reaction favored 0-aIkylation, these conditions led exclusively to A-p-toluenesulfonyl-2-oxazolidone 265 as shown in Scheme 60. 

The reactions between nitrosobenzene and enamines as activated carbonyl compounds are known to provide aminoxylation or hydroxyamination products, depending on the catalyst used. In the absence of relatively strong acids such as carboxylic acids, the organocatalytic reaction of aldehydes with nitrosobenzene led to hydroxyamination products exclusively. This phenomenon was checked by Maruoka and Kano by performing the precedent reaction in the presence of a closely related catalyst which did not bear a carboxylic... 

Conversion of aldehydes to nitriles using hydroxyamine and /7-nitrobenzonitrile sequentially. 

Catalyst 14a (20mol%) led to products 71 (R = H) in moderate yields and high enantiomeric excesses (40-75%, ee 91-99%) in the reaction of nitrosobenzene (70a) with Unear aldehydes in dichloromethane at 0°C [66a]. For this reaction, DFT calculations showed that the free activation energy AG for the non-catalyzed hydroxyamination was higher than that obtained in the presence of water or N,N-dimethylhydroxyamine, which mimics product 71 or its precursor. In addition, the AG values found for the catalyzed aminoxylation process are higher than those of the hydroxyamination. In this case, the observed (S)-preference for product 71 was rationalized by proposing an enamine intermediate with steric control approach from the Si face. Further calculations on the mechanism proposed that the lowest energy barrier proceeds via a trons-enol intermediate [66b], formed by... 

Also, A-hydroxy- 3-amino alcohols 44 (R = H, Scheme 4.6) were achieved in high yields and enantioselectivities using axially chiral secondary amine catalyst 46a (10 mol%) to perform the hydroxyamination of linear aldehydes 42 with nitrosobenzene (43a, Ar=Ph), with excellent results (77-90%, 97-99% ee) [45]. Due to the instability of the resulting hydroxyamination product, in situ reduction to the corresponding alcohol was carried out using NaBH. ... 

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