Substitution hydroxylamines

Compounds of the type R NH—OR are named (1) as alkoxyamino derivatives of compound R H, (2) as A, 0-substituted hydroxylamines, (3) as alkoxyamines (even if R is hydrogen), or (4) by the prefix aminooxy- when another substituent has priority for parent name. Examples of each type are... 

Furthermore the formation of <9-substituted hydroxylamines 12, e.g. by migration of an allyl or benzyl substituent, is possible ... 

The most widely employed methods for the synthesis of nitrones are the condensation of carbonyl compounds with A-hydroxylamines5 and the oxidation of A+V-di substituted hydroxylamines.5 9 Practical and reliable methods for the oxidation of more easily available secondary amines have become available only recently.10 11 12 13. These include reactions with stoichiometric oxidants not readily available, such as dimethyldioxirane10 or A-phenylsulfonyl-C-phenyloxaziridine,11 and oxidations with hydrogen peroxide catalyzed by Na2W044 12 or Se02.13 All these methods suffer from limitations in scope and substrate tolerance. For example, oxidations with dimethyldioxirane seem to be limited to arylmethanamines and the above mentioned catalytic oxidations have been reported (and we have experienced as well) to give... 

The formation of appreciable quantities (up to "oQ0% based on the initial additive concentration) of the grafted substituted hydroxylamine O W0PP as from reaction 7) in photo-degrading PPH can be demonstrated by indirect methods (10, 11). For example after the rapid loss of the initial concentration of a piperidine or its nitroxide in PPH film, heating the film immersed in isooctane for several hours at 100 C in the presence of oxygen causes the re-appearance of nitroxide in appreciable quantities as measured by e.s.r. spectroscopy (ll). This nitroxide most likely results from a reaction analogous to reaction 8 (l2). In addition we have observed the ) N-0-C band (at 1306 cm 1) in the infrared spectrum of irradiated, nitroxide-containing PP films by Fourier Transform IR spectroscopy (ll)., ... 

The substituted hydroxylamine from reaction 7 (>N0PP) may also contribute to the stabilization process by scavenging peroxyl radicals (reaction 9)- From a study of model compounds in k9... 

The substituted hydroxylamine C NOPP from reaction 7) can take part in various dark reactions, even at ambient temperature. From a study of the low molecular weight model I in the liquid phase, two decomposition pathways are possible (reaction 8) (12). The products from the disproportionation reaction 8a were only observed in the absence of a radical trap such as O2. In a given solvent ks kaa-Uo (solvent air saturated and degassed respectively). Both k8a and ke were found to increase by an order of magnitude on going from a non-polar solvent (iso-octane) to a polar solvent (methanol or tert.-butyl hydro peroxide, BuOOH). 

The cycloaddition, reduction and oxidation reactions emanating from a,/J-unsatu-rated nitroalkenes provide easy access to a vast array of functionalities that include nitroalkanes, N-substituted hydroxylamines, amines, ketones, oximes, and a-substi-tuted oximes and ketones [73-75], Consequently, there are numerous possibilities of using these in situ generated nitroalkenes for the preparation of valuable building blocks and synthetic precursors. 

Condensation of N -substituted hydroxylamines with aldehydes and ketones is widely used in the synthesis of various spin traps and biologically active nitrones (Fig. 2.5) (161-186). 

Addition of lithium derivatives of acetylenides (Li—C=C-C02R) to chiral nitrones proceeds with high stereoselectivity, giving a-acetylene substituted hydroxylamines (410a,b) (656). This reaction has been successfully applied to the synthesis of y-hydroxyamino-a, 3-ethylene substituted acids (411a,b), formed in the reduction of (410) with Zn in the presence of acid (657, 658), and to chiral 5-substituted-3-pyrroline-2-ones (412a,b) (Scheme 2.184) (658). 

The propensity of trialkyltin radicals to add to the terminal position of allenes has been applied in the synthesis of substituted hydroxylamines from N-oximinoallenes,... 

Bu3Sn Bu3Sn-20 21 Scheme 11.9 Formation of N-substituted hydroxylamines 24 and 25 [61]. 

An anodic azacyclization, producing tropane-related 11-substituted dibenzo[a,d]cycloheptimines 123, was recently developed by Karady et al. [136, 137]. This two-electron process is initiated by anodic oxidation of the O-substituted hydroxylamine 119 in nucleophilic solvent. It is proposed that the first one-electron oxidation leads to the aminium radical cation 120 which adds rapidly to the double bond. The electron-rich carbon radical 121 is readily oxidized to the carbocation 122. Selective nucleophilic attack on 122 from the less hindered exo-side yields the 11- substituted product 123. Depending on the... 

The aUcoxylamines have a >N—O—C substrucmre and may be considered O-substituted hydroxylamine ethers. The simplest example of these species is MeONH2 with a gas phase enthalpy of formation of —25.1 kJmol which was discussed in a previous section. Consider now the perfluorinated species (CF3)2N0CF2CF20N(CF3)2 and its synthesis shown in equation 9. 

Hydrolysis of nitrones, oximes and hydroxamic acids is frequently used as a final step in the preparation of substituted hydroxylamines. Although hydrolysis is the most commonly utilized method for oximes, oxime ethers and nitrones, formation of sensitive hydroxylamines can also be achieved under milder reaction conditions by treatment of... 

Reaction of hydroxylamine as well as O- and A-substituted hydroxylamines with aldehydes 63 results in formation of oximes and/or oxyiminium salts of type 64 (equation 42). Subsequent reaction with carbon, nitrogen, oxygen or phosphorous nucleophiles provides A-substituted hydroxylamines of type 65. 

In this context Miller " has demonstrated that all these issues could be overcome by hydroxamic-acids-based heteroatom activation.Therefore, S-halo or /S-hydroxy carboxylic acids 148a and 148b are converted to the corresponding hydroxamates 149a and 149b by active ester condensation with 0-substituted hydroxylamines (Scheme 69). Since chiral... 

Often, the use of expensive O-substituted hydroxylamines and the azodicarboxylates could be avoided by direct hydroxaminolysis of protected amino acid esters 151 with hydroxylamine itself, followed by in situ acylation and finally substitution of Ph3P/CCl4/ EtsN for PhsP/DEAD during the cyclization step from 152 to 153 (Scheme 70) . 

O-linked polymer-bound Af-substituted hydroxylamines are prepared by reduction of resin-bound oximes with borane-pyridine complex in the presence of dichloroacetic acid (Scheme 94). Other reducing systems commonly used for imine or oxime reduction are ineffective, including borane-pyridine in the presence of acetic acid. Subsequently, the A-substituted products are acylated and cleaved from the resin to afford Af-substituted hydroxamic acids 220. ... 

Electrophilic C-amination with 0-substituted hydroxylamines, oximes and O-substituted oximes... 

Substituted hydroxylamines 1-5 (R = R = H) and their A-mono- or A,A-disub-stituted derivatives 1-5 have been used extensively for electrophilic amination of both carbanions and enolates since the first report in 1938 on the use of 0-methylhydroxylamine 1 (R = Me) for conversion of Grignard reagents to primary amines. Oximes 7 (Z = H) have found limited applicability as amination reagents for carbon nucleophiles and then-use was first reported in 1907. Ketone 0-sulfonyloximes 7 (Z = SO2R) have recently been developed. 

This chapter on electrophilic amination using O-substituted hydroxylamines 1-5 and oximes 7 is focused on the various methods that have been reported for the amination of carbon nucleophiles. Synthetic aspects and applications of the methods for C—N bond formation are accompanied by a brief discussion of the reaction mechanisms. The preparation of O-substituted hydroxylamines and oximes has not been considered in detail. This review covers the literature up to August 2007 and is partly based on reviews on the electrophilic amination of carbanions and a-amination of carbonyl compounds. ... 

There are quite a large number of reported methods on the amination of carbon nucleophiles with O-substituted hydroxylamines 1-5 (R = = H) and their A-mono- and... 

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