Bromonitrile oxide

Dihydromuscimol (49) is a conformationally restricted analogue of the physiologically important neurotransmitter y-aminobutyric acid (GABA) and has been prepared using the cycloaddition of dibromoformaldoxime to A-Boc-allylamine followed by N-deprotection with sodium hydroxide (Scheme 6.52) (278). The individual enantiomers of dihydromuscimol were obtained by reaction of the bromonitrile oxide with (5)-( + )-l,2-0-isopropylidene-3-butene-l,2-diol, followed by separation of the diastereoisomeric mixture (erythro/threo 76 24), hydrolysis of respective isomers, and transformation of the glycol moiety into an amino group (279). 

Let us now consider the synthesis of isoxazole 4.28, a drug for the treatment of bronchial asthma. The most direct preparation of isoxazolyl ketone 4.24 is the cycloaddition of unstable bromonitrile oxide 4.22 (prepared in situ by dehydrobromination of 4.21) with acetylenic ketone 4.23. Observe the regioselectivity of this reaction. Both electron-donating and electron-withdrawing groups on the acetylenic components in such cycloadditions tend to occur at the C5 position in the final isoxazole and not at C4. Bromination of ketone 4.24 affords bromoketone 4.25 which is 4.23 n... 

Bromonitrile oxide, see Formonitrrle oxide, bromo-Bronchodilators... 

A useful route to 3-bromo-isoxazoles rests on the cycloaddition of bromonitrile oxide. ... 

An unusual influence of water on the rate of 1,3-dipolar cydoadditions was first observed when 2,6-dichlorobenzonitrile N-oxide was allowed to react with 2,5-di-methyl-p-benzoquinone [50]. Likewise, bromonitrile oxide, generated in water at acidic pH, gave cycloadducts effidendy with water-soluble alkenes and alkynes [51]. In highly aqueous media remarkable accelerations for the cycloaddition of phenyl azide to norbomene were observed [52]. 

Bacher et al. reported the synthesis of a potentially active anti-inflammatory steroid, 16o -carbomethoxyprednisolone 225, via bromonitrile oxide (221) cycloaddition to steroidal enones 220a,b (Scheme 53) [ 155]. The bromo-isoxazoline 222b was subjected to reductive cleavage and the resulting nitrile 223 was hydrolyzed and esterified to afford 225. Although direct displacement of bromide in 222 by methoxide was not feasible, the authors succeeded in the above transformation via protection/deprotection of the primary alcohol. However, all attempts to transform methoxyisoxazoline 224 to the ester 225 via reductive cleavage of the N-0 bond proved futile. 

Sodium hydrogen carbonate 3-Bromo-l,2,4-oxadiazoles from nitriles 1,3-Dipolar cycloaddition with bromonitrile oxide... 

The adducts (102) were obtained as a mixture of anti- and -isomers in a 76 24 ratio by cycloaddition of bromonitrile oxide to the alkene (101), After separation they were converted into the two enantiomers of dihydromuscimol (103) (Scheme 17). The pyrrole... 

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