Hydroxylamines, addition

The two major methods of preparation are the cycloaddition of nitrile oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamines. Additional methods include reaction of /3-haloketones and hydroxylamine, the reaction of ylides with nitrile oxides by activation of alkyl nitro compounds from isoxazoline AT-oxides (methoxides, etc.) and miscellaneous syntheses (62HC(i7)i). 

Allylboronates of type 103 react with equivalent amounts of aldoximes 102 (equation 73) giving allylhydroxylamines 104 in good yields. Similar reactions of aldoximes and glyoxylate oxime ethers with allyl bromide and indium also provide hydroxylamines. Additions of substituted allyl boronates to oximes produce mixtures of stereoisomers with ratio highly dependent on the steric size of substituents in both molecules. Addition of allyltri-n-butyltin to aldoxime ether 105 (equation 74) was found to proceed with a considerable diastereoselectivity. 

As an alternative to an olefination method, the Cope elimination can be used as a preparative method for unsymmetrical hydroxylamines. Addition of unsymmetrical secondary amine 41 to a,p-unsaturated compounds gave access to compound 42, which underwent oxidation and Cope elimination to yield the unsymmetrical hydroxylamine product 44.16... 

The utility of the organocatalytic hydroxylamine addition has been demonstrated with the preparation of a wide range of interesting enantioenriched compounds such as, P-antino acids [345,346], P-amino alcohols [345,346], 1,3-diamines [346], and different five- and six-membered nitrogen-containing heterocycles [347], as depicted in Schane 2.122 for the enantioselective synthesis of the alkaloid (+)-Angustureine... 

The hydroxylamine addition reaction was used for the preparation of P-N-hydroxyaminophenylpropionic acid (115) (Scheme 26) from cinnamic acid 148). Prolonged heating of a mixture of (115) and hydroxylamine gives the appropriate P-amino acid 150). 

Aldehyde analysis based on bisulfite or hydroxylamine addition involves a nucleophilic attack on the carbonyl groups. As shown in Table 6. the aldehyde content determined this way is only half of what is to be expected from the periodate consumption and of what is determined via iodine oxidation in alkaline medium . The latter method does not involve a nucleophilic attack at the aldehyde carbon atoms and is valid for hemiacetal determination as well. 

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