Heterogeneous Enantioselective Synthesis Of Chromans Via The Oxa-michael-michael Cascade Reaction Synergically Catalyzed By Grafted Chiral Bases And Inherent Hydroxyls On Mesoporous Silica Surface

Chiral chromans compounds are considered as an important class of heterocycles that exsit in many natural products and synthetic analogues.Recently chiral chromans have emerged as attractive synthetic targets since they were found to exhibit various biological activities.The chiral catalysts for the enantioselective synthesis of chiral benzopyran with the advantage of atom economy and well performance become the focus of the rearch.The acid-base bifunctional catalysts have been used as the synthetic strategy toward chiral chromans.In most cases,for double-sites homogeneous catalyst,it often could not avoid the problem of mutual deactivation of acidic and basic sites.Herein,we propose heterogeneous acid-base synergic catalysis for the asymmetric synthesis of chiral chromans,which employs a heterogeneous bifunctional catalyst with inherent achiral silanols of mesoporous silica as acidic sites and immobilized chiral amines as basic sites,conforming the trend of green chemistry.At the same time,the challenges in the synthesis of chiral chromans derivatives by asymmetric cascade reaction are to be managed by using the heterogeneous bifunctional catalysts illustrated here.Our studies have shown that:1.The chiral amine initially selected for immobilization is(S)-2-allyloxymethyl-pyrrolidine.To further enhance the catalytic efficiency,the other heterogeneous catalysts elaborately tuning the steric hindrance and the type of chiral amines were designed.The molar ratio of surface silanol to immobilized amines for each heterogeneous catalyst ranges from 5:1 to 10:1,demonstrating there are enough-OH groups around basic sites to establish the acid-base cooperation as expected.2.The catalysts have been found to afford enhanced activity and excellent enantiomeric excess in the asymmetric oxa-Michael-Michael cascade reaction between 2-nitrovinyl phenol and 3-methyl-2-butenal.Researches clearly reveal that well results were achieved by the acidic-basic synergies of the bifunctional catalyst.The benzopyran product has been afforded 97%ee on the designed catalyst SBA-Py-Diph using(S)-2-(Allyloxy-diphenyl-methyl)-pyrrolidine as basic site.The reusability of the heterogeneous catalyst designed here was also investigated.SBA-Py-Diph was recycled by simple filtration and re-used for catalytic runs.Well results are preserved in three recycle runs and the catalyst preserved the long-range ordered mesoporous structures and the periodic structure.3.The heterogeneous bifunctional catalysts designed in this work could be extended to the asymmetric oxa-Michael-Michael cascade reaction between 2-(2-nitrovinyl)-phenols and 3-phenyl-2-propynal which serve as a challenging substrate of rich electron.The benzopyran product has been afforded up to 80%yield and 96%ee.