On the reaction of sterically hindered α,β-unsaturated ketones with hydroxylamine: preparation of 5-hydroxy derivatives of isoxazolidine and 4,5-dihydroisoxazole

A Simple Environmentally Friendly Method for the Synthesis of Hydroxyisoxazolidine Derivatives

“…Mavrov and Firgang [5] explained the extra set of signals by an intramolecular hydrogen bond (or its lack). This sound quite probably taking into consideration observed contact through space for regioisomers between the − OH and the − NH group.…”

“…[1,5,[7][8][9] For the last fifty years, there have been few articles about the synthesis of hydroxyl isoxazolidines from unsaturated carbonyl compounds and hydroxylamine (or its derivatives/ analogs). [4,5,[17][18][19][20][21][22][23][24][25][26][27][28][29] The formation of 5-hydroxyisoxazolidines easily occurred in neutral pH at room temperature (in rather an anhydrous condition), few examples of 3-hydroxyisoxazolidines synthesis are also known, but only for benzohydroxyamic acid and its analogs (p-NO 2 , p-Br and 2,3,5-(CH 3 ) 3 ). Hydroxy isoxazolidines are rather unstable (decompose when exposed to light and upon heating) and undergo chain-ring tautomerism.…”

“…The isoxazolidine scaffold can be treated as unusual β-amino acids, mimetic of carbohydrates, PNAs, nucleosides, and steroids analogs. [1][2][3] Moreover, isoxazolidines are interesting intermediates in organic chemistry-by reductive cleavage of a ring, a lot of bifunctional compounds can be efficiently formed (for more details see [1,[4][5][6] ).…”

“…For the hydroxyisoxazolidine derivatives the “green approach” is often skipped. The most common reagents are alkali hydroxides, metal complexes and toxic organic solvents, such as toluene [1,5,7–9] …”

“…Formation hydroxyisoxazolidines in the reaction of enones and hydroxylamine was tested only by Belly (aliphatic enones, scheme 2) [28] and Mavrov and Firgang (aliphatic‐aromatic enones, scheme 3). [5,29] Mavrov and Firgang tested several bases and only for NaOH observed the formation of 5‐hydroxy isoxazolidine with low to moderate yield. Mavrov in 1998 also reported the formation of 3‐hydroxy isoxazolidines (two examples) in the reaction of hydroxylamine and arylideneketones, but no proof was given to confirm the structure of this regioisomer [29] …”