Organocatalytic synthesis of 5‐hydroxyisoxazolidine catalyzed by camphor sulfonyl hydrazines through aza‐Michael addition/cyclization

Abstract

A series of chiral 5‐hydroxy isoxazolidines has been successfully synthesized through camphor sulfonyl hydrazine‐catalyzed asymmetric aza‐Michael addition reaction between N,O‐protected hydroxyamines and enals. Moderate yields with moderate to good enantioselectivities (up to 96% enantiomeric excess [ee]) were achieved. It provides an alternative asymmetric approach to preparing isoxazolidine derivatives.

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

“…We have used ᴅʟ-proline for three reasons: first, it provides the target compounds 1 and 2 in their racemic form, second, it is able to catalyze the conjugate addition between N -EWG-protected hydroxylamines and enals effectively, and third, based on our experience, the products obtained by the proline catalysis are of higher purity (after purification by silica gel column chromatography), than those synthesized by other methods [ 16 ]. Definitely, the effective asymmetric organocatalytic conjugate additions of hydroxylamines to enals using various catalysts provide access to enantiomerically enriched isoxazolidin-5-ols [ 18 – 24 ], which, if needed can be converted into the desired pyrrolidine alkaloids. Treatment of 8 with Tf 2 O in the presence of 2-fluoropyridine in NMP at room temperature afforded 2,3-dihydroisoxazole 9 in good 68% yield.…”

A Simple Environmentally Friendly Method for the Synthesis of Hydroxyisoxazolidine Derivatives

“…[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.…”