Hydroxylamine, 0- electrophilic / /-aminations

Boche, G., R. H. Sommerlade and F. Bosold. 1986. N-Aryl-0-(diphenylphosphinoyl)hydroxylamines electrophilic amination of amines to hydrazines a model reaction for the carcinogenicity of aromatic amines. Angew. Chem. Int. Ed. Engl. 25 562-563. 

The reaction of 2-chloro-4,5-dihydroimidazole 347 with hydroxylamine-O-sulfonic acid gives 2-hydroxylamino-4,5-dihydroimidazolium-O-sulfonate 348, which reacts with aldehydes and cyclic ketones to give the imidazo[l,2-f] fused 4,5-dihydro-l,2,4-oxadiazoles 350 (Scheme 58). Mechanistically, the reaction may be explained by the reaction of an imidazoline NH with the carbonyl followed by intramolecular electrophilic amination of the anionic oxygen present in the resultant intermediate 349 and elimination of the sulfate group <2003JOC4791>. 

The efficiencies of 0-(diphenylphosphinoyl)hydroxylamine and hydroxylamine-O-sulphonic acid as electrophilic aminating agents have been compared96. The conversion of... 

Direct formation of 5,5-dihydro-5-iminothianthrene by reaction with hydroxylamine mesitylsulfonate presumably involves, first, electrophilic amination at sulfur (74TL1973). Electrophilic S-bromination (see also Section III, A, 3, b) must be presumed to initiate the conversion of thianth-rene into the sulfurane 25 by reaction with bromine in the presence of the alcohol (RfOH = l,l,l,3,3,3-hexafluoro-2-phenyl-2-propanol) (77JOC3222). 

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. ... 

Recently, a direct kinetic study on the amination of substituted phenyhnagnesium bromides using Af,Af-dimethyl O-mesitylenesulfonyl hydroxylamine 3b as amination reagent has been reported by Erdik and Ate Ulkii . Rate data, the Hammett relationship and activation entropy support an Sn2 displacement of the carbon nucleophile on the electrophilic nitrogen. These results are consistent with the competition kinetics for electrophilic amination of substituted phenyl Grignard reagents with O-methylhydroxylamine In. ... 

There are a few reports on the use of oximes as electrophilic amination reagents. Since 1984, ketone O-sulfonyloxknes have found applicability as amino transfer reagents to car-banions. In the reaction of organometaUic compounds with oximes, carbanions attack the carbonyl carbon of the oxime, giving Af-substituted hydroxylamines as addition products (Scheme 53, path a). However, a number of scattered reports have been also published on the formation of aziridines by a-deprotonation, followed by addition (path b) or formation of azirines by a-deprotonation before addition (path c). Addition of carbanions to azirines also yields aziridines, which are hydrolyzed to a-aminoalcohols. 

The discussion in this chapter highlights the performance of O-substituted hydroxylamines and oximes as electrophilic amino transfer reagents. In conclusion, the scope of electrophilic amination will be greatly enhanced by developing new O-substituted hydroxylamines and oximes and further improvements in electrophilic amination would be of great synthetic interest. 

Hydroxylamino-4,5-dihydroimidazolium-<9-sulfonate 303 is prepared by reacting 2-chloro-4,5-dihydroimidazole with hydroxylamine-O-sulfonic acid. Reaction of 303 with carbon disulfide in the presence of triethylamine presumably proceeds via intermediate 304 to yield the 6,7-dihydro-5//-imidazo[2,l-c][l,2,4]thiadiazole-3-thione 305 by a tandem nucleophilic addition-electrophilic amination reaction <03JOC4791>. In an interesting photochemical reaction, irradiation of 5-phenyl-1,2,4-thiadiazole 306 results in the formation of benzonitrile 307 <03JOC4855>. 

The Schmitz reaction can be unsuccessful in sterically demanding environments in such circumstances, the electrophilic aminating agent reacts faster with ammonia than with hindered ketones <1965JA2665>. Consequently, the synthesis of 2-azi-camphane 64, a compound which is unobtainable under standard conditions <1996TL6647>, was achieved by slow diaziridination of camphor imine hydrochloride 63 (rather than camphor itself) with hydroxylamine-O-sulfonic acid (HOSA)-ammonia, followed by iodine-mediated oxidation (Scheme 22) <2001S379>. 

To further extend fhe substitution pattern of fhese building blocks, benzarmelated N-amino-N-heterocycles were prepared Electrophilic amination of indole, 2-mefhylindole, or carbazole using hydroxylamine-O-sulfonic acid [25] yielded fhe corresponding N-amino-indole 17, -2-methyhndole 18, and -carbazole 19, respectively. However, attempting the same reaction with 2,7-dimethyhndole or dibenza-zepine (iminostilbene) failed, most likely due to steric hindrance. 

There are a number of important methods worthy of merit for the synthesis of phosphorylglycines. Thus, electrophilic amination of diethyl l-(ethoxycarbonyl)methylphosphonate proceeds in one simple operation via the sodium salt in THF or DME. A variety of aminating agents are used with variable yields, such as 0-mesitylenesulfonylhydroxylamine (39 7%), chloramine (23-84%), and diphenyl (O-hydroxylamine)phosphine oxide (60%). Diethyl 1-ethoxycarbonyl- or l-(tert-butoxycarbonyl)methylphosphonate may also be efficiently transformed into oxime or diazo derivatives and then converted to an amine by a further reduction step. The oximes are prepared from EtONO via the sodium diethyl l-(tert-butoxycarbonyl)methylphosphonate (17% or 36%), from NOCl and diethyl l-(ethoxycarbonyl)methylphosphonate in the presence of tEtOljMg, Al-Hg, or Al(O7-Pr)3, 8 from NOCl and diethyl l-(methoxycarbonyl)ethylphosphonate, ° or from NOCl/ROH and diethyl l-tchlorocarbonyl)mclhy I phosphonate. ... 

The majority of diaziridine syntheses proceed by intramolecular electrophilic amination in a geminal compound 84/ ° an aminallike °° compound from an amine, a carbonyl compound, and an electrophilic aminating agent like chloramine or hydroxylamine-O-sulfonic acid. The different ways of diaziridine synthesis differ mainly in the timing of the build-up of this geminal intermediate 84, from which the diaziridine 85 is isolated. 

The electrophilic amination of the sodium salts of a-unsubstituted 3-dicarbonyl compounds is one of the few examples of an amination where hydroxylamine O-sulfonic acid gives useful yields (Eq. 161) 472 with two equivalents of the substrate, pyrroles are formed.472,473 Chloramine,62 64 O-arylhydroxylamines,93,124,474 O-sulfonylhydroxylamines,134 and 0-(diarylphos-phinoyl)hydroxylamines106,139,475 have also been employed, although a low yield and formation of the hydroxylation product as a side product have been reported in one instance with (4-Me0C6H4)2P(0)0NH2.145 Some of these animations use chiral auxiliaries in the substrates with modest diastereoselectivities,124,475,476 but these have been superseded by the catalytic methods discussed below. 

An ortho amide 78 of propiolic acid has been prepared it readily condenses with acetylacetone (equation 11). Novel A,A-bis(trimethylsilyl)ynamines 80 are obtained by electrophilic amination of lithium acetylides with the hydroxylamine derivative 79 a,b The action of lead tetraacetate on di(alk-l-ynyl)mercury compounds or alk-1-ynyltrimethylstannanes gives highly unstable alk-l-ynyllead triacetates 81 (R = pj. 

Electrophilic amination of the sulfur atom to give zwitterionic A(-ylides (68) or l-aminopyrimidin-2-ones has been carried out employing 1-aminopyrimi-dine-2-thiones and 3,3-pentamethyleneoxaziridine or hydroxylamine-O-sulfonic acid (93T(49)3767). 4,6-Dichloro-S-pyrimidinecarboxaldehydes have been employed to construct thieno 2,3-r/ pyrimidines (69) (93JHC(30)1065). 

Electrophilic aminations with 0-substituted hydroxylamines H2NOAr and H2NOCOAr (Ar = mesityl or dinitromesityl) have been reviewed . Numerous heterocycles have been transformed by the mesityl derivative 79 into the salts 80 and tatiary amines into 81. The action of 0-(2,4-dinitrophenyl)hydroxylamine 82 [Ar = 2,4-(02N)2C6H3] on aldehydes RCHO (R = CsHis, Ph, 4-MeOC6H4 and 4-O2NC6H4) results in oximes, which form nitriles under basic conditions . 

Electrophilic amination can be achieved using hydroxylamine-based ammonia equivalents. The preferred conditions for this transformation utilize sodium hydride in dioxane. Addition of the anion to 0-(p-nitrobenzoyl)hydroxylamine (NbzONH2) generates theiV-amino-2-oxazolidinone (eq 44). Although the amino compound can be isolated, typically the product is converted to the more stable hydrazone. 

Handling, Storage, and Precautions reagents for electrophilic aminations with f (f tdimethyl(dialkyl) functionality like (1) are much more stable than their NH2 analogs. Thus the pure compound (1) can be stored at —30°C for at least 1 year. Impure (1) (and related compounds), however, may decompose at rt, as also reported for fV,yV-diethyl-0-(mesitylsulfonyl)hydroxylamine. ... 

Electrophilic amination of organolithium compounds with methyllithium-methoxamine or amination of higher order cuprates by N,0-bis(trimethylsilyl)hydroxylamine. Also amination of aryllithium by vinyl azides. ... 

Umpolung Cross-Coupling Johnson and coworkers reported electrophilic amination of organozinc nsing o-benzoyl hydroxylamine as electrophilic nitrogen (Scheme 20.26) [56]. This process allows the facile synthesis of sterically hindered amines via ort/io-metalation/frans-metalation/catalytic amination. 

Electrophilic Amination of Alkoxides. Generation of the lithium alkoxide of benzyl alcohol with LHMDS in THF at —78 °C, followed by the addition of oxaziridine 1 and slow warming to ambient temperature, delivered an essentially quantitative yield of the desired 0-benzyl-iV-Boc-hydroxylamine (eq 30). ... 

Benzotriazole-related methodology publications appeared in 2006. Reaction of 1-formylbenzotriazole with triphenylphosphine/carbon tetrachloride afforded l-(2,2-dichlorovinyl)benzotriazole, where lithiation followed addition of electrophiles gave a variety of functionalized M-(ethynyl)benzotriazoles <06T3794>. Novel mono- and symmetrical di-/V-hydroxy- and IV-aminoguanidines were readily prepared from the reaction of diverse hydroxylamines or hydrazines with reagent classes di(benzotriazol-l-yl)methanimine, (bis-benzotriazol-1 -y 1-methy lene)amines, benzotriazole-1 -carboxamidines, benzotriazole-1 -... 

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