Inherent Achiral Hydroxyls On Mesoporous Cooperative With Grafted Chiral Bases Promoting Catalysis Of Asymmetric Domino Reactions

Chiral compounds have important significance in the field of medicine. How to obtain optical complex molecules in a simple and efficient way is of great interest in fine chemical industry. Asymmetry domino reactions gain widespread attention owing to its economy and atomicity, and have also been proved to be an efficient way to obtain chiral compounds. To our best knowledge, acid-base bifunctional catalysts not only can improve the effectiveness of overall reaction, but also expand the type of cascade reaction by acid-base synergy. Although homogeneous acid-base catalysts have been reported to promote reactions successfully with good activity and high enantioselectivity, the urgent issue of mutual deactivation of acidic and basic sites is still in challenge. As heterogeneous acid-base bifunctional catalysts can settle the urgent issue, more attention was given by scientists. However, researches on heterogeneous acid-base bifunctional catalyst for catalytic asymmetric domino reaction are still in infancy. Here, we construct heterogeneous acid-base bifunctional catalysts with inherent achiral hydroxyls of mesoporous silica as acidic sites, and immobilized chiral amines as basic sites. Then we study the heterogeneous acid-base bifunctional catalysts in asymmetry domino reactions. The main research contents included:1. SBA-15-SH/SBA-15-Br with abundant hydroxyl was selected as the acid support and quinine (Q) was initially selected as immobilized amines to construct heterogeneous bifunctional catalyst SBA-15-Q. To further enhance the catalytic efficiency and get a simpler structure, the other two heterogeneous catalysts (SBA-15-AEP and SBA-15-PY) were designed. The structure of heterogeneous catalysts were study by detailed research:C CP/MAS proved the successful immobilization of functional groups on SBA-15. The result of XRD and N2 adsorption-desorption experiments revealed that SBA-15, SBA-15-SH, SBA-15-Br and heterogeneous catalysts have the well-ordered mesoporous structure. TEM also displayed the well-ordered hexagonally symmetric channel structure of all samples. The silanol density of SBA-15-SH and SBA-15-Br determined by the deconvolution of 29Si MAS NMR, EA and BET analysis.2. Heterogeneous bifunctional catalyst SBA-15-AEP with different pore size has been found to afford excellent activity and enantiomeric excess in asymmetry Knoevenagel-P-Michael domino reactions by the synergetic effect. Study found that the catalyst with large pore size is more available to wide substrate of Knoevenagel-P-Michael domino reaction.3. Heterogeneous bifunctional catalysts afford excellent activity and enantiomeric excess in aza-Michael-Henry and Michael-intramolecular cyclization domino reaction. The study found that:a) archiral hydroxyl group and chiral base can synergistically promote the asymmetry domino reactions; b) heterogeneous acid-base bifunctional catalysts have good activity and excellent selectivity for asymmetric aza-Michael-Henry domino reactions, the yield of quinoline products up to 85% and ee of up to 99%; c) heterogeneous acid-base bifunctional catalysts were also used to catalyze the asymmetric Michael-cyclization reaction between malononitrile and 2-hydroxychalcone, the yield and ee reach 99% and 95%; d) In Michael-cyclization reaction between 4-hydroxycoumarin and benzylidenemalononitrile, the ee reach 88%; e) In Michael-cyclization reaction between trans-2-hydroxy-β-nitrostyrene and butyraldehyde, SBA-15-PY catalyst has good catalytic effect in Michael-intramolecular cyclization reaction, but there is still room to further explore.