D-甘露醇衍生的手性亚磷酸酯配体:合成及应用于铑催化α-脱氢氨基酸酯不对称氢化

Chiral Diphosphite Ligands Derived from D-mannitol:Synthesis and Their Application in the Rh-Catalyzed Enantioselective Hydrogenation of α-Dehydroamino Acid Esters

以1,2:5,6-双亚环己基-D-甘露醇为手性骨架,合成含有联苯基团的新型手性tropos配体;分别以1,2:5,6-双异丙叉-D-甘露醇和1,2:5,6-双亚环己基-D-甘露醇为原料,合成系列双齿亚磷酸酯配体,将这些配体应用于铑催化α-乙酰氨基肉桂酸甲酯5a和α-苯酰氨基肉桂酸甲酯5b氢化反应中,考察配体结构,溶剂,底物/催化剂的摩尔比对反应对映选择性的影响,优化了反应条件;在底物是α-乙酰胺基肉桂酸甲酯时,配体的双异丙叉骨架与(R)-联萘部分是匹配组合,反应对映选择性高达93.5%.在优化的反应条件下,尝试七个苯环含不同取代基团的底物,无论供电子基团在芳环的邻位还是对位,其氢化产物的对映选择性均高于相应位置为吸电子基团的.

A new tropos ligand based on the 1,2:5,6-di-O-cyclohexylidene-D-mannitol and 2,2'-dihydroxybiphenyl was easily synthesized.And some chiral diphosphite ligands based on D-mannitol derivatives were also prepared.They were all successfully applied to the Rh-catalyzed asymmetric hydrogenation of methyl(Z)-2-acetamidocinnamate(5a) and methyl(Z)-2-benzoylamidocinnamate(5b).The effect of ligand structure,solvent and the ratio of substrate /catalyst on enantioselectivity were examined.The stereochemically matched combination of 1,2:5,6-di-O-isopropylidene-D-mannitol and(R)-binaphthyl was essential to afford 93.5% ee for the hydrogenation of5 a.Hydrogenation of α-dehydroamino acid esters with electron-donating substituents on the phenyl ring gave higher enantioselectivity than those with electron-withdrawing substituents,no matter these substituents are at the ortho or para position of the phenyl ring.