Isoxazolines, from

Pyrroles from 1,4-dicarbonyl compounds and ammonia isoxazolines from olefins and nitrile oxides. 

In theory, three isoxazolines are capable of existence 2-isoxazoline (2), 3-isoxazoline and 4-isoxazoline. The position of the double bond may also be designated by the use of the prefix A with an appropriate numerical superscript. Of these only the 2-isoxazolines have been investigated in any detail. The preparation of the first isoxazoline, 3,5-diphenyl-2-isoxazoline, from the reaction of )3-chloro-)3-phenylpropiophenone with hydroxylamine was reported in 1895 (1895CB957). Two major syntheses of 2-isoxazolines are the cycloaddition of nitrile A-oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamine. Since 2-isoxazolines are readily oxidized to isoxazoles and possess some of the unique properties of isoxazoles, they also serve as key intermediates for the synthesis of other heterocycles and natural products. 

A number of clever syntheses have employed this strategy. Entry 8 in Scheme 6.5 shows the final steps in the synthesis of the alkaloid pseudotropine. The proper stereochemical orientation of the hydroxyl group is ensured by the structure of the isoxazoline from which it is formed by reduction. Entry 9 portrays the early stages of a synthesis of the biologically important molecule biotin. 

Transformations of Isoxazolines from Intramolecular Cycloadditions via Isoxazolinium Salts... 

Both nltroaldol15 and t,3-dipolar cycloaddition products (e.g., isoxazolines, from alkenes)13 14 have shown that nitroacetaldehyde diethyl acetal 1 constitutes a versatile C2 building block in organic synthesis, notably what concerns amino sugar... 

Another method used in the diastereoselective synthesis of isoxazo-lines involved reactions of the iron complexed trienes (115) with nitrile oxides to give the cycloadducts (116) and (117) in a ratio of ca. 9 1 (Scheme 53) (89TL6517). There have been reports on the use of baker s yeast in the enantioselective synthesis of isoxazolines from 4-vinyIpyridine and arylnitrile oxides, and of the enhancement of that selectivity using jS-cyclodextrin (90TL3201 92PACI141). 

Between the three classes of dihydroderivatives, the 2-isoxazolines are by far the most easily prepared and widely studied. The preparation of the first derivative, 3,5-diphenyl-2-isoxazoline from /3-chloro-/3-phenylpropiophenone and hydroxylamine, was reported in 1895 <1895CB957> however, the synthesis of saturated compounds was not described until 1918 <1918CB192> and isoxazolidine itself was prepared in 1942 <1942JCS432>. 

Synthesis of isoxazolidines and isoxazolines from nitrones by 1,3-dipolar cycloaddition on solid supports 05CSR507. 

Isoxazolines from Nitro Compounds Synthesis and Applications... 

Namboothiri INN, Rastogi N (2008) Isoxazolines from Nitro Compounds Synthesis and Applications. 12 1-44 Natarajan R, see Basak SC (2006) 3 39-80... 

Construction of stmcturally inspiring spiroisoxazolines 13COS661. Functional 3-arylisoxazoles and 3-aryl-2-isoxazolines from reaction of aryl nitrile oxides and enolates ... 

---