奎宁催化不对称4-甲基苯甲醛与亚磷酸二乙酯的Pudovik反应

Quinine catalyzed asymmetric Pudovik reaction of 4-methylbenzaldehyde with diethyl phosphite

以天然来源的奎宁为手性催化剂,不对称催化4-甲基苯甲醛与亚磷酸二乙酯的Pudovik反应,得到具有手性结构的(4-甲基苯基)(羟甲基)膦酸二乙酯。产物结构经;HNMR和ESI-MS进行表征,产物的对映体过量值(ee值)经手性高效液相色谱(HPLC)测定。考察影响产物(4-甲基苯基)(羟甲基)膦酸二乙酯的收率及选择性的主要因素,确定的最佳反应条件为:n(奎宁)∶n(4-甲基苯甲醛)=0.05∶1、n(亚磷酸二乙酯)∶n(4-甲基苯甲醛)=1.2∶1、反应溶剂为四氢呋喃、反应温度为20℃、反应时间为24h。在该最佳条件下,产物收率为87.2%(以4-甲基苯甲醛计),ee值为92.9%。

The asymmetric Pudovik reaction of 4-methylbenzaldehyde with diethyl phosphite was catalyzed with natural quinine as chiral catalyst.Diethyl(hydroxy(p-tolyl)methyl)phosphonate with chiral structure was obtained.The structure of the product was characterized by~1HNMR and ESI-MS,and the enantiomeric excess value(ee value)of the product was determined by chiral HPLC.The optimum reaction conditions were determined as follows:the dosage of catalyst was n(quinine)∶n(4-methylbenzaldehyde)=0.05∶1;the material mole ratio was n(diethyl phosphite)∶n(4-methylbenzaldehyde)=1.2∶1;the solvent was tetrahydrofuran;reaction was at 20℃for 24 h.Under these reaction conditions,the yield of product was 87.2%(based on 4-methylbenzaldehyde)and ee value was up to 92.9%.