Isoxazolin-5-imines

Isoxazolin-5-imines were produced by nitrile oxide addition to cyanoacetates (62HC(17)l,p.7), by the reaction of nitrones with phenylacetonitrile (74CB13), and by base addition of nitrosobenzene to nitriles (Scheme 148) (72LA(762)154). 

Isoxazolin-5-imine, 2,3,4-triphenyl-photolysis, 6, 43 Isoxazolin-5-imines synthesis, 6, 105 2-Isoxazolin-5-ol synthesis, 6, 100 Isoxazolinols synthesis, 6, 100-102 Isoxazolin-3-one, 5-methyl-2-phenyl-rearrangement, 6, 43 Isoxazolin-5-one, 4-acyl-reactions... 

Spiro-isoxazoline 57 (Scheme 16) undergoes thermolytic rearrangement followed immediately by cyclization of the intermediate enaminone to bicyclic 58 (89J(P1)1253). Imine 59 when heated gives iminium salt 60, hence providing a new and efficient route to parent substance 2 (03T3099). 

Imines can be photoreduced by hydrogen donors such as propan-2-ol, but in some cases it is clear that a small amount of carbonyl compound (arising from hydrolysis of the imine) is necessary to initiate the process. For example, N-alkytirnines of benzaldehyde give elhane-1.2-diamine derivatives on irradiation in 95% ethanol (5.6). but they are inert when irradiated in a perfectly dry alcohol. The C=N chromophore is capable of abstracting a hydrogen atom, and both the photoreduclion of a tetrahydropyridine (5.7) and the photoaddition of p-xylene to an isoxazoline (5.6) occur by such a direct reaction. 

Likewise, trifluoromethyl-substituted nitrile imines [172] and nitrile oxides [173,174, 775] have been used to synthesize trifluoromethyl substituted five-membered ring systems of the pyrazole, isomzole, isoxazoline, and 1,2,4-oxadiazole... 

Vinyl boronates 228 undergo 1,3-dipolar cycloaddition with aryl hydroximinoyl chloride 229 to furnish the imine-oxide 231. The boronate moiety is highly labile under the reaction conditions and it undergoes protonolysis to yield isoxazolines 232. Alternatively, the boronates could be oxidized with hydroperoxides or sodium percarbonate to furnish the 4-hydroxyisoxazolines 233 in good yield (Scheme 39) <2000T965>. 

This is believed to involve a free radical cleavage of the isoxazoline to the [3-hydroxy imine 11, which then undergoes hydrolysis (Scheme 15.5).5... 

The neurotropic activity of germatranes, germsesquioxanes, germyl-substituted amines, imines, hydroxamic acids, isoxazolines and organogermanium derivatives of furan and adamantane has been studied4,5,10,40,44,50-54. 

The N—O bond of isoxazolines can easily be cleaved via reduction. It is for this reason that isoxazolines are interesting synthetic intermediates. y-Amino alcohols are formed by reduction with LiAlH4 (for an example, see Figure 15.46, left). Hydrogenolysis of isoxazolines catalyzed by Raney nickel yields /j-hydroxy imines, which undergo hydrolysis to / -hydroxy-carbonyl compounds in the presence of boric acid (Figure 15.46, right). 

Secondary amines can be oxidized at the N-H bond to hydroxylamines and nitroxides, and via nitrones via C-N oxidation. Nitrones are valuable intermediates in the production of isoxazolines. Initial C-N oxidation of secondary amines gives imines which can react further to oxaziridines. The latter can be converted to nitrones, and both to amides. Primary amines are oxidized at the N-H bond to mono-substituted hydroxylamines, which are readily converted further to nitroso and nitro compounds by the more activated peroxygen... 

Imines can be hydrolyzed in quantitative yield by use of boric acid in ethanol under reflux [1]. Imines that are susceptible to intra- and intermolecular attack in the presence of other catalysts have been successfully hydrolyzed by use of boric acid [2], The conversion of isoxazolines into y3-hydroxy ketones and yS-hydroxy esters involves hydrogenolysis of the N-O bond and imine hydrolysis in a single step [3]. In the presence of boric acid, racemization is inhibited (Eq. 1) [3a]. 

Hydrogenation of 2-isoxazolines over Raney nickel as catalyst and in the presence of acids often leads first to 1,3-hydroxyimines, and then, through hydrolysis, to 1,3-hydroxycarbonyl compounds. In some cases the stereochemical integrity of the starting material is maintained, but in others hydrolysis of the intermediate imines may cause scrambling of stereochemistry at the a-carbon atom. Rapid protonation of the imine function minimizes this possibility and the use of Lewis acids, such as boron trichloride or aluminum trichloride which release hydrochloric acid on contact with moist methanol, is frequently recommended. Boric acid serves a similar purpose and is effective in, for example, the stereocontrolled reductive ring opening of the 2-isoxazoline (135) en route to crispatic acid (136 Scheme 6). ... 

Indoles have been prepared from reactions of o-aminophenylketones with reactive , or stable " arsonium ylides. Oxo-stabilized ylides reacted with 2-chloro-oximes to give trans-5-acyl-A -isoxazolines, and isoxazoles have been obtained from reactive arsonium ylides and a-isonitrosoketones, and from triphenylarsonium methylide and nitrile oxides The latter ylide reacts similarly with nitrile imines to give pyrazoles. With triphenylarsonium benzylides and benzoylylides,benzene diazonium salts give 1,3,4,6-substituted 1,4-dihydro-1,2,4,5-tetrazines in a reaction in which initial coupling of the reagents is followed by a dimerisation. ... 

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