Ring Opening of 3‐Bromo‐2‐Isoxazolines to β‐Hydroxy Nitriles

An Approach to Mimicking the Sesquiterpene Cyclase Phase by Nickel-Promoted Diene/Alkyne Cooligomerization

“…Cycloadditions with 1,1-dibromoformaldoxime have been shown to proceed with high regioselectivity at room temperature, which was crucial to avoid Cope rearrangement. The intended endgame would then involve fragmentation of the resulting isoxazoline moieties to the bis-β-hydroxynitrile rac - 43 with Raney-Ni , or TMSCl/NaI . Following elimination of the secondary alcohols, a vinyl nitrile cross-coupling based closely on the work of Dankwardt could be employed in order to access the lowly oxidized germacrene skeleton 44 …”

“…The intended endgame would then involve fragmentation of the resulting isoxazoline moieties to the bis-β-hydroxynitrile rac-43 with Raney-Ni 96,97 or TMSCl/NaI. 98 Following elimination of the secondary alcohols, a vinyl nitrile crosscoupling based closely on the work of Dankwardt could be employed in order to access the lowly oxidized germacrene skeleton 44. 99 In practice, 1,1-dibromoformaldoxime afforded the desired isoxazoline rac-45, unfortunately as the minor regioisomer (2.7:1 ratio, Scheme 8).…”

Pentafulvene for the Synthesis of Complex Natural Products: Total Syntheses of (±)‐Pallambins A and B

“…Methods for functionalizing bromoisoxazolines are rare. Most commonly, they are converted into β ‐hydroxy nitriles using either TMSCl/NaI13a or NaSEt13b or reduced to β ‐hydroxy amines. After extensive experimentation, including transition‐metal‐catalyzed couplings, radical dehalogenations, or substitution reactions with vinyl anions, no effective functionalization of 19 could be established.…”

Synthesis and Reactivity of 3‐Halo‐4,5‐dihydroisoxazoles: An Overview

“…3‐bromo‐Δ 2 ‐isoxazolines are versatile masked cis ‐disubstituted structural templates that can be easily inserted into the target molecules and exploited as intermediates for the generation of diverse chemical motifs. In particular, in contrast to other 3‐substituted‐Δ 2 ‐isoxazolines, this exquisite nucleus allows easy access to γ‐amino alcohols, [66,72,108] β‐hydroxy nitriles [62,105,109–111] and β‐hydroxy esters, depending on the reaction conditions [112] . Furthermore, the synthetic strategy involving 1,3‐dipolar cycloaddition with DBF followed by reductive ring‐opening is particularly valuable for many reasons, especially because it ensures high yields with an often predictable regio‐ and stereoselective outcome.…”

“…Kociolek and Kalbarczyk [109] proposed another valuable alternative for the ring‐opening of different 3‐bromo‐Δ 2 ‐isoxazolines ( 32 ) to β‐OH nitriles ( 34 ) by using NaI and two different Lewis acids (trimethylsilyl iodide or p ‐toluenesulfonic acid) in MeCN, obtaining good to excellent yields. The Lewis acid was found to be essential, because the reaction with the only presence of NaI does not occur, and its role consists in the coordination of the isoxazolinic oxygen to favour the iodine ion attack on the bromine atom, thus releasing IBr (Scheme 15).…”