Dipolar Cycloadditions of HMF- based nitrones: stepwise and multicomponent reactions, stereochemical outcome and structural scope

Lianjie Wang (1) , Charlie Verrier (1) , Mohammed Ahmar (1) , Yves Queneau (1)

1 COB - Chimie Organique et Bioorganique

The straightforward preparation of new 3-furanyl isoxazolidines by 1,3-dipolar cycloaddition of 5-hydroxymetylfurfural (HMF) derived nitrones with electrodeficient olefins is investigated. The study addresses the stepwise reaction, with isolation of the intermediate nitrone, and the multicomponent protocol involving directly HMF and other reaction partners and reagents. Optimal reaction parameters (solvent, temperature, stoichiometry) for the stepwise and multicomponent reactions are defined, resulting on a choice a clean and direct conditions leading to cycloadducts in good yields. Isopropanol is found the most appropriate solvents both in terms of acceptability and efficiency depending on the solubility of the different substrates and on specific requirements for either the stepwise or multicomponent protocols. The stereochemical outcome of the reaction and the structural scope with respect to various dipolarophiles (acrylates, cycloalkenones, acrylamides, acrylonitrile), variously substituted hydroxylamines, using HMF and O-substituted HMF analogs are also fully assessed. The structural considerations allowing more regioselective reactions are also defined. This study provides the basic elements necessary for considering the use of HMF in such strategies.

Keywords: Dipolar cycloadditions; nitrones; isoxazolidines; HMF; bio-based chemistry

Domains: Chemical Sciences; Organic chemistry

Lianjie Wang, Charlie Verrier, Mohammed Ahmar, Yves Queneau. Dipolar Cycloadditions of HMF- based nitrones: stepwise and multicomponent reactions, stereochemical outcome and structural scope. Green Chemistry, 2020, pp.1 - 17. ⟨10.1039/D0GC03004J⟩. ⟨hal-02959119⟩