Cyclodextrin-catalyzed Retro-Henry Reaction

Supramolecular catalysis is a form of catalytic reaction similar to that of natural enzymes,which is mainly accomplished through non-covalent interactions between host and guest molecules.Cyclodextrins（CDs）are among the most commonly used hosts in supramolecular catalysis,which have a rigid stereostructure with a hydrophilic outer wall and a hydrophobic inner cavity.CDs can wrap a wide range of guest molecules,including hydrophobic organic molecules,thereby promoting the water solubility of guest molecules and enabling the reaction to proceed in water.Nevertheless,the catalytic performance of CDs is usually hurt by their insufficient water solubility and functional homogeneity.Structural modification of CDs could be a promising solution.In this dissertation,five Per-6-substituted amino-CDs were designed and synthesized for catalytic retro-Henry reaction in water.The main research work of this dissertation is as follows:1.Five functionalized amino-CDs（Per-6-NH₂-α-CD,Per-6-NH₂-β-CD,Per-6-NH₂-γ-CD,Per-6-EDA-β-CD,Per-6-DME-β-CD）were synthesized and used to catalyze the retro-Henry reaction.（1）The retro-Henry reaction of 1-（4-methoxyphenyl）-2-nitroethane-1-ol in water was studied as the template reaction,and the reaction conditions were optimized.（2）The scope of the reaction substrate was investigated.（3）According to the existing reports and the characteristics of CDs,the possible reaction mechanism was proposed.A total of 15β-nitro alcohols were involved in retro-Henry reaction.It was found that Per-6-DME-β-CD could efficiently catalyze the retro-Henry reaction in water with a catalytic amount of 1 mol%（up to 99%yield）,and with a wide substrate scope.2.Five synthesized functionalized amino-CDs were used to catalyze the synthesis of cyclohexenones.（1）The catalyst screening and reaction conditions optimization were carried out with1-（4-methoxyphenyl）-2-nitroethylene and acetone as model substrates.（2）The scope of the reaction substrate was investigated.（3）The catalytic mechanism was studied by NMR and MS analysis.Nine cyclohexenones were successfully synthesized.It was found that Per-6-NH₂-β-CD as a catalyst could efficiently catalyze the synthesis of cyclohexenones at 60°C in water with a catalytic amount of 20 mol%（up to 99%yield）,and with a wide range of substrates.The study of the reaction mechanism shows that the process may undergo steps such as retro-Henry reaction,aldol reaction and Michael addition reaction.In conclusion,a series of functionalized amino-CDs were designed and synthesized,and their catalytic retro-Henry reaction and synthesis of cyclohexenones were studied.The catalytic system is highly efficient and environmentally benign.It could inspire new ideas in the CD-based supramolecular catalysis.