Research On The Asymmetric Synthesis Of Optically Active β-phenyl-α,β-Epoxymethyl Propionate

Optically active β-phenyl-α,β-epoxymethylpropionate is the key intermediate to synth-esis vairous of chiral pharmaceutical drugs. Heretofore, lots of asymmetric epoxidationmethods has been reported about α,β-unsaturated aldehydes、ketones and amides. They allobtained highly conversion and enantiomeric excess. Because the influence of ester group,it’s become difficulty to introduce oxirane in the molecular of β-phenyl-α,β-epoxymethyl-propionate, so the asymmetric epoxidation method of α,β-unsaturated ester was rarely rep-orted. Thus, research the asymmetric epoxidation method of the chemical structure similar-ly compounds have some significance on the chiral pharmaceutical drugs, which syntheticprecursor is optically active α,β-epoxy carboxylate.The sharpless asymmetric epoxidation reaction of cinnamic alcohol has been widelyutilized in asymmetric synthesis of optically active β-phenyl-α,β-epoxy methylpropionate.The enantiomeric excess of obtained (-)-(2R,3S)-3-phenyl-2,3-epoxymethylpropionate ismore than95%. Unfortunately, the total conversion is only28.4%. Moreover, both theintermediate epoxy propanol a and acid b are instable, easily to be decomposed.The optically active β-phenyl-α,β-epoxymethylpropionate should be prepared from β-pheyl-α,β-methacrylate, which formed by esterification of β-phenyl-α,β-acrylic acid. In ord-er to get target products, we should to select appropriate oxidants, design and synthesizevarious chiral ligands catalyst.30%H2O2、11%NaClO、TBHP、30%Peroxyltrifluoroacetic acid、Trifluoroaceton-Ox-one etc oxidants, have been studied in the epoxidation reaction. But they all can not get β-phenyl-α,β-epoxymethylpropionate. Finally, select m-CPBA as oxidant, control the react-ion temperature in0～10℃、pH=7.5、the ratio of m-CPBA and methyl cinnamate at1:5, obt-ained β-phenyl-α,β-epoxymethylpropionate, whose reaction conversion reach to34.14%.The chiral ligand catalyst derived from quinine contains N、O hydrogen bond center,which could form hydrogen bond with substrates to increase enantioselectivity. The prepar-ation of quinine N-substituted quaternary ammonium salt maybe usable the following condi-tions: the ratio of quinine and halohydrocarbon is1:1.5、acetone-alcohol as mixture solve-nt、reaction temperature is60℃、reaction time is5h. Using DMF-NaH system can get N-s-ubstituted9-ether quinine quaternary ammonium salt. So, we design and synthesized9-hy-droxyl N-substituted quinine quaternary ammonium salt and9-ether N-substituted quininequaternary ammonium salt. The amount of two categories chiral ligands is totally16and th-e conversion reached to71.17%～76.11%. The products can characterized by IR、HRMS、1H-NMR、specific rotation、element analysis and melting point. There are9products havenot been reported in literature.The asymmetric epoxidation reaction of β-phenyl-α,β-methacrylate carry out by m-CPBA and quinine quaternary ammonium salt catalysts. The specific rotation of obtained opti-cally active β-phenyl-α,β-epoxymethylpropionate intercomparison with the literature stan-dard value. The results showed that, both products are (+)-(2S,3R)-3-phenyl-2,3-epoxyme-thylpropionate, ee%=0.57～4.67.The experiment showed that, the enantioselectivity of9-ether N-substituted quinine qu-aternary ammonium salt is higher than9-hydroxyl N-substituted quinine quaternary amm-onium salt; the enantioselectivity of aliphatichalides-quinine quaternary ammonium salt is p-oorer than aromatichalides-quinine quaternary ammonium salt. The enantioselectivity of QN-b-15in the all obtained ligand catalysts is best, and the enantioselectivity of QN-b-16isworst.