Asymmetric a-aminoxylation

Hayashi, Y. Yamaguchi, H., Sumiya, T. and Shoji, M. Direct Proline-catalyzed Asymmetric a-Aminoxylation of Ketones. Angew. Chem. Int. Ed. 2004, 43, 1112 -1114. 

This asymmetric a-aminoxylation can be applied to a wide range of aldehydes (Table 6.1) and six-membered cyclic ketones (Table 6.2). Because of the easy conversion of a-aminoxy moiety to the a-hydroxy group, " operational simplicity, and the... 

Table 6.1 Proline-catalyzed direct asymmetric a-aminoxylation of aldehydes.

Recently, some extensive research has been devoted to exploring a diastereo-selective and enantioselective route for the synthesis of a-hydroxyaldehydes or a-hydroxyketones because they are important building blocks for the construction of complex natural products and biologically active molecules [91]. In parallel with the transition-metal-catalyzed asymmetric nitroso-aldol reaction [92], much interest has also been expressed towards the proline-catalyzed direct asymmetric a-aminoxylation of aldehydes or ketones for the synthesis of optically active a-hydroxyladehydes and a-hydroxyketones [93]. Wang [94] and Huang [95] independently reported an L-proline-catalyzed asymmetric a-aminoxylation reaction in ionic liquids, whereby it was found tliat aldehydes and ketones could undergo... 

Yamamoto and coworkers have developed an asymmetric a-aminoxylation of cyclic tributyltin enolates using nitrosobenzene (5.85) as oxygen source in the presence of Lewis acidic 1 1 silver-BINAP complexes. For example, the enolate (5.86) is converted into the a-aminoxyketone with high ee using this procedure. Cleavage of the N-0 bond is then effected with no racemization, using catalytic copper sulfate in methanol. 

Scheme 22.22 CIL 62-catalyzed asymmetric a-aminoxylation and a-amination reactions of carbonyl compounds.

Recently, the same authors discovered that CIL 65 could serve as an efficient promoter in asymmetric a-aminoxylation of carbonyl compounds with nitrosoben-zene in IL media [86]. They managed to recycle and reuse the catalytic system 65/[bmim]BF4 up to five times however, the enantioselectivities and yields of products 68 decreased with each recycle and the reaction time had to be increased to achieve complete conversion of the starting material. The authors explained the... 

Scheme 22.23 Formation of off-side oxazolidinone 70 in CIL 65

Zhong G (2003) A facile and rapid route to highly enantiopure 1,2-diols by novel catalytic asymmetric alpha-aminoxylation of aldehydes. Angew Chem Int Ed Engl 42 4247 1250... 

Strategy A. The enamine strategy to asymmetric transformations of carbonyl compounds is also exploited for the construction of carbon-heteroatom bonds using proline as catalyst, dissolved in ionic liquid media. Thus, a highly enantioselective a-aminoxylation of aldehydes and ketones has been reported based on the use of nitrosobenzene as the aminoxylating agent and catalysed by proline in [bmim] and [pmim] [BF4] and The reaction reported in Figure 6 affords poorer values in terms of yield and reaction rate when carried out in molecular solvents. Conversely, proline dissolved in the IL is recovered up to 6 times without appreciable loss of activity. 

Aldehydes and ketones could be asymmetrically a-amino-oxylated [36, 37] or a-aminated [38] to corresponding poly-functional compounds 8 and 9 by proline-catalyzed reactions with nitrosobenzene or diethyl azodicarboxylate in molten imidazoUum salts (Scheme 22.5). As compared to those in common solvents, the yields of a-aminoxylation products 8 of both aldehydes and ketones improved significantly in the IL medium and the enantioselectivity was excellent Yields and enantiomeric enrichment of hydrazino-aldehydes 9 were somewhat lower. The ionic environment considerably accelerated the processes and the (S)-proline/IL system could be quantitatively recovered after completion of the aminoxylation reaction and reused (5-6 times) without any loss of catalytic performance. Aldehyde-derived products 8 and 9 (R = H) could be reduced to chiral 1,2-diol derivatives 10 or configurationally stable heterocycles 11, which are valuable intermediates in asymmetric synthesis. 

For example, in 2004, Wang and coworkers reported a series of asymmetric transformations, for example, a-aminoxylation, Mannich reactions, and a-sulfenylation, under the catalysis of pyrrolidine trifluoromethanesulfonamide 36 the product yields and diastereo- and enantioselectivities are quite good in most... 

Among the existing methods for the asymmetric synthesis of chiral a-hydroxy carbonyl compounds, the direct enantioselective a-aminoxylation of carbonyl compounds is one of the most important strategies to achieve this purpose. Although its nitrogen versus oxygen electrophihc reactivity in nitroso compounds should be carefully controlled through the election of appropriate catalysts and reaction conditions. 

Asymmetric line broadening is commonly observed for aminoxyl radicals, which are therefore used in a wide variety of spin label and spin probe studies (see Section 18.6.5.2). 

In 2009, Wang et al. developed an asymmetric synthesis of 3-hydroxyl-2-alkanones via a tandem organocatalytic aminoxylation of aldehydes and a chemoselective diazomethane homologation. An accelerating effect of water was observed for the aminoxylation catalysed by L-proline, while MgCl2 served... 

In addition, an asymmetric aminoxylation reaction of aldehydes by nitroso-benzene catalysed by a binaphthyl-based chiral amino sulfonamide was reported by Maruoka et As shown in Scheme 4.9, combinations of excellent yields... 

On the other hand, however, trimethylsilyl-protected catalyst 18 was suitable for the asymmetric bromination of aldehydes, and the resulting a-bromoaldehydes can be diastereoselectively transformed into the corresponding bromohydrin in one-pot (Scheme 7.31) (54). An additional utility of catalyst 18 was highlighted by application to the development of the direct aminoxylation of aldehydes with an oxoammonium salt generated from 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) by in situ oxidation with benzoyl peroxide, allowing for the highly enantioselective synthesis of stable a-aminoxy aldehydes, which could subsequently be reduced to the corresponding alcohol (55). 

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