0-Acylhydroxylamine

A-Mono- and iV,iV-disubstituted 0-benzoylhydroxylamines 2a-i recently developed for amination of organozinc and Grignard reagents and 0-acylhydroxylamines 2j-l for amination of enolates have been listed in Table 2. 0-Benzoylhydroxylamines were prepared by Berman and Johnson " by oxidation of primary and secondary amines with... 

TABLE 2. 0-Acylhydroxylamine-type electrophilic amination reagents... 

The use of 0-acylhydroxylamine-type reagents for amination of a-metallated carbonyl compounds is limited. The use of 0-mesitoylhydroxylamine 2j or 0-(3,5-dinitromesitoyl) hydroxylamine 2k in the amination of the enolate derived from 3-methylbutanoic acid was unsuccessful ". 

The reduction of 0-acyl oximes to 0-acylhydroxylamines also is accomplished under mild conditions with pyridine-BHs/HCl, NaBHsCN/HCl, and NaBHsCN/AcOH in a similar fashion as with other oxime derivatives. In addition, BH3 (1 equiv.) and the combination of EtsSiH/TFA also effects efficient reduction. With the former reagent, rearrangement to N-acylhydroxylamines has been observed (equation 3). Representative examples of 0-acyl oxime reductions are presented in Table 12. The related derivatives nitrones are also reduced by LAH, or NaBHsCN/H to hydroxylamines (equation 4).202... 

Acyl derivatives, RCO—NH—OH and HjN—O—CO—R, are named as A-hydroxy derivatives of amides and as O-acylhydroxylamines, respectively. The former may also be named as hydroxamic acids. Examples are A-hydroxyacetamide for CH3CO—NH—OH and O-acetylhydrox-ylamine for HjN—O—CO—CH3. Further substituents are denoted by prefixes with O- and/or A-locants. For example, C5H5NH—O—C2H5 would be O-ethyl-A-phenylhydroxylamine or A-ethox-ylaniline. 

Methylhydroxyurea (28, Fig. 7.5) oxidizes oxyHb to metHb and reduces metHb to deoxyHb but neither of these reactions produces HbNO, further supporting the mechanism depicted in Scheme 7.16 for the formation of NO and HbNO from the reactions of hydroxyurea and hemoglobin [115]. The O-methyl group of 27 prevents the association and further reaction of 27 with the heme iron [115]. Scheme 7.16 predicts the redox chemistry observed during the reaction of 28 with hemoglobin and the failure to detect HbNO shows the inability of 28 or any derivative radicals to transfer NO during these reactions [115]. These results indicate that nitric oxide transfer in these reactions of hydroxyurea requires an unsubstituted acylhydroxylamine (-NHOH) group. 

An analogous method was used by Endo and colleagues in a-amination of unreactive carboxylic acids. Treatment of iV-acylhydroxylamine O-carbamates 92 by KHMDS or LDA followed by [3,3]-sigmatropic rearrangement and decarboxylation provided a-amino acid analogues 93 (equation 29). 

V-Acylhydroxylamines are oxidized to the interesting intermediates acylnitroso compounds by the action of Dess-Martin periodinane.59... 

Aliphatic nitroso compounds can be prepared from IV-alkylhydioxylamines oxidation widi bromine, chlorine or sodium hypochlorite in weakly acidic solution, reaction with potassium dichromate in acetic or sulfuric acid, and by oxidation widi yellow mercury(II) oxide in suspension in an organic solvent. Silver carbonate on Celite has also been used to prepare aliphatic nitroso compounds, such as ni-trosocyclohexane, in high yield from the corresponding hydroxylamines." Aqueous sodium periodate and tetraalkylanunonium periodates, which are soluble in organic solvents, are the reagents most commonly used for the oxidation of hydroxamic acids and IV-acylhydroxylamines to acylnitroso compounds... 

When acylnitroso derivatives are employed as dienophiles in the cycloaddition, the re-gioselectivity of the reaction is inverted with respect to the mode of addition of nitrosobenzene. Thus l,2-dihydro-A -methoxycarbonylpyridine. by reaction with V-acylhydroxylamines in the presence of tetraalkylammonium periodate at 78 r C in dichloromethane, leads to the corresponding 2-oxa-3,5-diazabicyclo[2.2.2]oct-7-enes in good yield. The regiochemistry of the cycloaddition product 2 was determined by 13C NMR84-86. 

Good results were obtained by oxidation of the /V-acylhydroxylamine derived from (/ )-methoxymandelic acid with the Swern reagent at — 78 "C in dichloromethane100. 

Following another synthetic pathway, an intramolecular cycloaddition was carried out by treating the JV-acylhydroxylamine 5 a with tetrapropylammonium periodate in chloroform. Under these conditions intramolecular [4 + 2] cycloaddition occurs with complete simple diastereoselectivity to give the corresponding bicyclic dihydro-1,2-oxazine cis-6a as the sole product118-121. However, when the IV-acyl hydroxy larnine bears a substitutent R1 the stereocontrol is incomplete. 

Finally, low diastereoselectivity was observed in the intramolecular cycloaddition starting from the (V-acylhydroxylamine 7 in order to obtain a tetracyclic adduct 8. A d.r. of only 67 33 was observed and this has been explained on the basis of mechanistic considerations122. 

The Af-aryl-Af-acylhydroxylamines 289 and 290 rearrange to aminophenol derivatives in the presence of sulfonyl chlorides (equation 138) as well as of iodonium salts in a reaction similar to the benzidine rearrangement (equation 139). The A-aryl-N,0-diacylhydroxylamine 291 undergoes isomerization on heating to produce dibenzoylated aminophenol 292 (equation 140) . The Wallach rearrangement consists of isomerization of aromatic azoxy compounds 293 to form the hydroxyazobenzenes 294 on heating in... 

N -I henylmorpholine (Amination of an Arylzinc Derivative with an O-Acylhydroxylamine). This procedure is found in Organic Syntheses.111... 

A high reactivity of HAS with diacylperoxides was observed in low-temperature oxidation of PO and yields O-acylhydroxylamines [206] ... 

Inactive A-acylhydroxylamines 135 result in free-radical scavenging of acyl radicals by nitroxides (Scheme 24, pathway a) [126, 173, 174, 191]. Alternative pathways b and c starting with NOH were proposed as well [26] and include reactivity with aldehydes or carboxylic acids formed in oxidized PO. Aldehydes generate hemiacetals 136 in the first step and are transformed into 135 after scavenging ROO. ... 

Dihydro-2//-l,2,4-oxadiazin-5(6//)-ones (222) are synthesized in 50-80% yield by acid-catalyzed condensation of arylaldehydes with (7-alky 1-A-acylhydroxylamines (e.g., (221)) (Equation... 

Formation of 1,2,4-oxadiazines occurs by acid-catalyzed ring expansion of a-aziridino oximes and dioximes, and by 1,3-dipolar cycloaddition of arylcarbonitrile oxides and 2-acyl-2//-azirines (Section 6.14.10). Preparation of l,2,4-oxadiazin-5-ones can be achieved by ring closure of A-carboxymethyl and A-alkoxycarbonylmethyl amidoximes (Section 6.14.9.1.1), by the acid-catalyzed condensation of arylaldehydes with O-alkyl-A-acylhydroxylamines (Section 6.14.9.2.3.1), and by reaction of A-hydroxyureas or amidoximes with a two-carbon fragment such as an a-halo ester or an acyl halide (Section 6.14.9.2.2.1). 

Alkylations. There are reports on the alkylation of Al-acylhydroxylamines, 1,2,4-tricizole, and glycine methyl ester using DBU as base. In the last case, an a,N,Al-triallyl derivative results because of a [2.3]Stevens rearrangement. 

Triorganotin acetylacetonates and iV-acylhydroxylaminates exhibit contrasting behaviour, and have the cis trigonal bipyramidal structures, (65) and (66). 

The synthesis of a series of hexahydro derivatives (44 R = Ph, OPh, CH2OC6H4—Cl-p, CH2C6H4—CN-p, OCsH —SMe-o), as well as the iV-tosyl analogue, through the electrochemical reduction/dialkylation of various -acylhydroxylamines with 1,6-dibromohexane (or l-bromo-6-chlorohexane) has been reported (Equation (10)) <89JAP01221371, 89Japoi221372, 90Japo2229175>. 

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