Reactions aminoxylation

In 2013, Mamoka and coworkers published a one-pot cross double Mannich reaction of acetaldehyde catalyzed by a binaphthyl-based aminosulfonamide [4]. The functionalized diamines were obtained as a single stereoisomer in moderate yields (45-57%) with excellent enantioselectivity (99%). The procedure was also extended to other electrophiles such as nitrosobenzene. Two examples of a one-pot Mannich reaction-aminoxylation were described, and the yn-p-amino-a-hydroxyaldehydes were obtained with excellent stereoselectivity (dr > 20 1, ee 99%). These reactions were performed by using a large excess of acetaldehyde to produce the single Mannich adduct, and the excess amount of acetaldehyde was removed by evaporation before the addition of the second electrophile. This operational procedure lowers the synthetic appeal of this strategy, and, as a result, it is in the limit of the field of MBFTs. 

Another strategy to perform an electrophilic amination of a carbonyl compound is through the reaction of an enamine or enolate with a nitroso derivative. As the nitroso compound contains two nucleophilic sites two possible processes could take place. The first one, generally promoted by the presence of carboxylic groups in the catalysts, is the C-O bond forming reaction (aminoxylation or 0-nitroso aldol... 

There is some evidence in favor ° of the captodative effect, some of it is from ESR studies. However, there is also experimental and theoretical evidence against it. There is evidence that while FCH2 and p2CH are more stable than CH3, the radical Cp3- is less stable that is, the presence of the third F destabilizes the radical. " Certain radicals with the unpaired electron not on a carbon are akso very stable. Diphenylpicrylhydrazyl is a solid that can be kept for years. We have already mentioned nitroxide radicals. Compound 29 is a nitroxide radical so stable that reactions can be performed on it without affecting the unpaired electron (the same is true for some of the chlorinated triarylmethyl radicals mentioned above ). ot-Trichloromethylbenzyl(rer/-butyl)aminoxyl (30) is extremely stable. In... 

In atmospheric chemistry, reactions between pure nitric oxide and a range of activated alkenes have been examined. However, no addition products were observed." Only in the presence of NO2 was addition to give jS-nitroalkyl radicals, followed by trapping to /3-nitronitroso compounds, observed. These final products can also trap other radicals to give aminoxyl radicals. 

Chiral non-racemic 0-(2-ketoalkyl) A-phenylhydroxylamines such as 115 (equation 84) can be prepared through catalytic enantioselective a-aminoxylation of carbonyl compounds catalyzed by proline. This reaction proceeds with a variety of ketones and aldehydes although it has been tried only with a nitrosobenzene component ... 

Additional clues confirm the radical nature of the reaction of BTNO with RH substrates. A Hammett correlation, obtained on plotting log A h for reaction of BTNO with p-substimted benzyl alcohols, gave a p value of —0.55 vs. a+. This small value, which is reasonable for a radical reaction, compares well with the p values ranging from —0.54 to —0.70 and obtained vs. the same substrates with the aminoxyl radicals generated from X-aryl-substituted HPIs (Table 5). In all cases better Hammett correlations were obtained vs. the values. Hence, a uniform pattern of selectivity emerges among these electrophilic >N—O" species in H-abstraction reactions. 

It will be useful to evaluate and compare the reactivity of additional aminoxyl radicals in the H-abstraction reaction in future investigations. 

At the end of this long fist of procedures, a few additional data from the recent literature are commented on. First of all, it is a common notion that a supported catalyst is easier to separate from the end products, and its re-use is facilitated. Accordingly, several reports deal with TEMPO immobilized on appropriate polymeric supports (i.e. PIPO) , or similar heterogeneous devices. Apart from the above anticipated advantages, the immobilized TEMPO leads to the same reactive intermediate (i.e. the oxoammonium) and gives the same reaction products seen before, thereby presenting no additional synthetic or mechanistic value. Then, some specialized TEMPO-like aminoxyl radicals begin to appear in the literature, in order to tackle specific needs. 

The reaction of 2,2,6,6-tetramethylpiperidyl radical with 02 has been studied using EPR at low temperature. Evidence indicates a possible reversible reaction with initial formation of the piperidylperoxyl radical followed by conversion to the aminoxyl... 

Singh, R. Tsuneda, T Hirao, K. An examination of density functionals on aldol, Mannich and a-aminoxylation reaction enthalpy calculations, Theor. Chem. Acc. 2011,130,153-160. 

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. 

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... 

Very recently, Pericas reported a new strategy to immobihze trans-4-hydroxypro-line onto an insoluble Merrifield-type polymer by exploiting Cu(I)-catalyzed 1,3-dipolar cycloaddition ( click chemistry ) [42]. The supported catalyst 25 was successfully employed in the a-aminoxylation of ketones and aldehydes (Scheme 8.13). Under the optimized reaction conditions (20mol%/cat, 2 equiv. ketone, DMF, 23 °C, 3 h), the reaction of cyclohexanone with nitrosobenzene catalyzed by 25 gave the product in 60% yield and 98% ee (Scheme 8.13 Equation a). It should be noted that the reaction rates of cyclic ketones with supported catalyst are faster than those reported with (S)-proline. The use of a supported catalyst allowed for a simplification of the work-up procedure, as the product could often be obtained after simple filtration of the catalyst and evaporation of the solvents. Furthermore, 25 was recycled up to three times without any decrease in either the chemical and/or stereochemical efficiency. 

In a similar way, Hawker and Hedrick [220] synthesized a-amino,cw-aminoxyl PS. Before performing the NMP of styrene, they synthesized a new protected amino diazoic initiator by reaction of N-(ferf-butoxycarbonyl)-4-aminophenol with a bisacid chloride diazo initiator. The resulting initiator was heated in the presence of styrene and TEMPO at 130 °C (Scheme 37). 

PAMAM scaffolds have been decorated with carbohydrates via oxime ligation [177], RAFT scaffolds have been functionalized with D-mannose, /V-acetylga-lactosamine and lactose via the reversed oxime ligation, i.e. the sugar molecules were aminoxylated (cf. Scheme 1) and then reacted in aqueous acetic acid with the RAFT scaffold provided on solid support and presenting four glyoxaldehyde functions. Excess sugar was recovered and RP-HPLC analysis of a reaction sample, cleaved from the resin, showed only the expected product [72],... 

Reaction is catalyzed with benzotriazole. Performing the reaction in EPR spectrometer ampule permitted to trace isomeric benzotriazolyl spin adducts 120 and 121. The latter transform to aminoxyl radical 122. Under... 

In the photoinduced cleavage of N-alkoxyamines, where the transient and the persistent radical are an alkyl and an aminoxyl radical, Fischer et al. used time-resolved CIDNP to clarify the mechanism of cross-termination and to determine the rate constant of the recombination. They concluded that disproportionation plays no role in this system, and that no unknovm side reactions occur. Later, Ananchenko and Fischer compared the recombinations of the transient ferf-butyl and 2-hydroxy-... 

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