A-Acylhydroxylamine

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). 

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. 

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... 

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 ". 

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). 

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. 

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 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... 

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... 

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

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. 

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>. 

Sodium cyanoborohydride-acetic acid and triethylsilane-trifluoroacetic acid have been found to be excellent reducing systems for oxime benzoates, providing a new general synthesis of O-acylhydroxylamines (Scheme 38). ... 

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