Organocatalysis “on water”. Regioselective [3 + 2]-cycloaddition of nitrones and allenolates

Abstract

The first example of a regioselective and organocatalyzed 1,3-dipolar cycloaddition reaction between conjugated alkynoates and nitrones "on water" is described.

Organic Synthesis “On Water”

“…53,54 Thus, nitrone 44 reacted with methyl propiolate 45 , providing the approximately 1:1 mixture of the trisubstituted isoxazoline 46 and hydroxylamine 47 in 90% combined yield. The yields were very low in toluene, benzene and dichloromethane.…”

Water—More Than Just a Green Solvent: A Stereoselective One‐Pot Access to All‐Chiral Tetrahydronaphthalenes in Aqueous Media

“…Inspired by the recent reports by the groups of Barbas10 and Ma6e that brine and water are good media for the organocatalytic Michael reactions of aldehydes and nitroolefins, we hypothesized that water might interact with the dipole of the reactant and direct the configuration of the [3+2] cycloaddition reaction 11. If the in situ formation of a 1,3‐dipole (nitrone) followed by an intramolecular cycloaddition could be carried out in water, it would represent a potent and greener approach to organic synthesis12 as most of the reactions used to form nitrones are dehydrations of substituted hydroxylamine and carbonyl compounds that require anhydrous conditions, dehydrating agents, or surfactant catalysts 13.…”

Green Protocols in Heterocycle Syntheses via 1,3-Dipolar Cycloadditions

“…Triphenylphospine and tertiary amines can be used to activate conjugated carbonyl alkynes toward 1,3-dipolar cycloaddition. In fact, β-phosphonium (or ammonium) allenolates perform as reactive dipolarophiles in aqueous 1,3-dipolar cycloadditions and have been used to give 2,3-dihydroisoxazole (Scheme 13) (Gonzalez-Cruz et al, 2006). The reaction increased the reaction yield up to 68% when LiCl was used and interestingly only one regioisomer was isolated, while no reaction was observed in toluene and DCM.…”