A?-Oxides rearrangement

Regioselective chlorination at C-5 of 3-pivaloyloxymethylpyrido[4,3- pyrimidine A -oxide 198 with POCI3 (100°C/2h) gave 199 via a Meisenheimer A -oxide rearrangement (Equation 15)<2004TL3737>. 

Trichloropyrazine may also be prepared by chlorination of 2,3-dichloro-pyrazine296 or, as previously mentioned, from triketopiperazine,273 296 but A-oxide rearrangement is probably the laboratory method of choice. A further application of A-oxide rearrangement for chloro-pyrazine preparation is taken from the work of Cragoe and his colleagues (Scheme 28).265... 

Aqueous permanganate converts l,3-dibenzyl-2-phenylimidazolidine into a mixture of benzamide and benzoic acid. When 1-alkyl-3-phenylimidazolidines are subjected to N-oxidation the unstable A-oxides rearrange to give tetrahydro-l,2,5-oxadiazines (180) via the ring-opened product (Scheme 89) (77LA956). 

A 5-alkoxypyridoL4,3-4]pyrimidin-4(3f/)-one has been synthesized via a selective A-oxidation followed by a regioselective Meisenheimer A-oxide rearrangement <04TL3737>. 1,2,3,4,5,6,7,8-Octahydroquinazolinediones and 3,4-dihydro-l/f-indeno l,2-rf]pyrimidine-2,5-diones were obtained by a modified Biginelli synthetic route <041JC135>. A series of l//-pyrazolo[3,4-af -... 

This reaction has been extended to a synthesis of 2-acetoxybenzodiazepine via an A-oxide rearrangement (eq 36). 

Within the cubane synthesis the initially produced cyclobutadiene moiety (see p. 329) is only stable as an iron(O) complex (M. Avram, 1964 G.F. Emerson, 1965 M.P. Cava, 1967). When this complex is destroyed by oxidation with cerium(lV) in the presence of a dienophilic quinone derivative, the cycloaddition takes place immediately. Irradiation leads to a further cyclobutane ring closure. The cubane synthesis also exemplifies another general approach to cyclobutane derivatives. This starts with cyclopentanone or cyclohexane-dione derivatives which are brominated and treated with strong base. A Favorskii rearrangement then leads to ring contraction (J.C. Barborak, 1966). 

Furthermore, the catalytic allylation of malonate with optically active (S)-( )-3-acetoxy-l-phenyl-1-butene (4) yields the (S)-( )-malonates 7 and 8 in a ratio of 92 8. Thus overall retention is observed in the catalytic reaction[23]. The intermediate complex 6 is formed by inversion. Then in the catalytic reaction of (5 )-(Z)-3-acetoxy-l-phenyl-l-butene (9) with malonate, the oxidative addition generates the complex 10, which has the sterically disfavored anti form. Then the n-a ir rearrangement (rotation) of the complex 10 moves the Pd from front to the rear side to give the favored syn complex 6, which has the same configuration as that from the (5 )-( )-acetate 4. Finally the (S)-( )-mal-onates 7 and 8 are obtained in a ratio of 90 10. Thus the reaction of (Z)-acetate 9 proceeds by inversion, n-a-ir rearrangement and inversion of configuration accompanied by Z to isomerization[24]. 

When alkoxypyridazine 1-oxides are heated alone or in the presence of p-toluenesulfonic acid the methyl group migrates from the methoxy group to the A-oxide group. In this manner, 4-methoxypyridazine 1-oxide rearranges to l-methoxypyridazin-4(l//)-one, 5-methoxypyridazine 1-oxide to 2-methylpyridazin-5(2//)-one 1-oxide and substituted 3,6-dimethoxypyridazine 1-oxides to l,3-dimethoxypyridazin-6(l//)-ones. 

A useful approach to the substitution of ring C—H positions lies in the activation of the heteroaromatic system by an A-oxide group, initiating a formal intramolecular redox reaction. 1-Methyllumazine 5-oxide reacts with acetic anhydride in a Katada rearrangement... 

However, the thermolysis of diacylfuroxans (429) yielded two types of nitrile Af-oxides. An uncrowded diacylfuroxan such as (429a) rearranged to the a- acyloximino nitrile A-oxide (430) the diacylfuroxan with bulky substituents such as in (429b) gave rise to the half molecule acyl nitrile Af-oxide (431). Both types of nitrile Af-oxides (431) and (430) have been trapped with DMAD and hexafluoro-2-butyne to give isoxazoles in good yield. These reactions are shown in Scheme 97. 

POLONOVSKY N-oxide Rearrangement Conversion of heterocyclic N-oxIdes to a-acetoxyheterocycles... 

Kubota and co-workers describe a novel oxidative rearrangement of the diosphenol (58) of 17iS-hydroxyandrost-4-ene-2,3-dione to the A-nor-A -1,2-diketone (59) in 33 % yield by the action of specially prep d manganese dioxide in boiling acetone. The rate of ring contraction is very sensitive to the source of the oxidant, and a trace of dilute sulfuric acid in the reaction mixture causes oxidative fission of ring A. 

Oxidative rearrangement of 5a-cholestan-3-one (62) with hydrogen peroxide and a catalytic amount of selenic acid affords 2a-carboxy-A-nor-5a-cholestane, isolated in about 35 % yield as the methyl ester (63)." However, the reaction gives a complex mixture of A-nor- and seco-acids, and under... 

Ring contraction by oxidative rearrangements of A-ring a-diketones by manganese dioxide... 

The formation of a library of 2-substituted quinolines employed a variation on the Boekelheide reaction. Treatment of A-oxide 41 with isobutylchloroformate did not result in the typical rearrangement. However, subsequent exposure to Grignard reagents resulted in loss of the carbonate with concomitant formation of the 2-substitute derivatives 42. 

A series of oxidative rearrangements of tetrahydro-j8-carbolines may be rationalized on the basis of a general reaction of 2,3-disub-stituted indoles which was recently recognized by Taylor. Attack at the 4a-position of the tetrahydrocarboline (341) by an electrophile yields the indolenine derivative 342, which is in equilibrium with the isomeric species 342a. Compounds of structure 342 and 342a can undergo a variety of reactions leading to different products. 

The amination of 2-chloropyridine-A-oxide (53) with potassium amide in liquid ammonia yielded a mixture of 2-(55) and 3-amino-pyridine-A-oxide (56) in 5-10% total yield.This rearrangement might be explained by an aryne mechanism involving 2,3-pyridyne-A-oxide (54). Since the structure of 56, with its quaternary nitrogen atom, is more analogous to that of 3-methoxybenzyne (39) than to that of 2,3-pyridyne (26), an orientation effect directing the amide ion to C-3 can be expected here. 

Another example of this rearrangement has been used to prepare 1,2,3-triazole 146 from furazanic phenylhydrazone 147 (Scheme 84) [93JCS(P1)2491]. Interestingly, furoxanic Z-phenylhydrazones 150 underwent thermal recyclization to 1,2,3-triazole A-oxides 152, evidently through intermediate 151. Treatment of the hydrazone 150 with rerr-BuOK leads to the nitromethyl derivative 149 [OOOMIl] (Scheme 84). Lead tetraacetate oxidation of 147 with subsequent Lewis acid treatment of the initially formed intermediate afforded indazole 148 (Scheme 84) (85JHC29). 

The electron impact positive ion spectrum of l,2,5-oxadiazolo[3,4-/]quinoline IV-oxide 46 shows the loss of N2O2 from the molecular ion, a process that must be followed by a substantial rearrangement to enable the observed loss of propyne-nitrile. This remarkable result apparently arises through a series of H-atom shifts which relocate the dehydroaromatic moiety in the heteroring (890MS465). 

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