R-(-)-α-环己基扁桃酸的不对称合成

Asymmetric Synthesis on R-(-)-α-Cyclohexyl-mandelic Acid

以R-(-)-扁桃酸和异丁醛作为R-(-)-α-环己基扁桃酸不对称合成的起始原料,得到第-步产品:顺式-(2R,5R)-2-异丙基-5-苯基-1,3-二氧杂环戊-4-酮(Ⅰ),有87.2%的收率。然后用环己酮作为亲电试剂,引入环己基。接着采用先加氯化亚砜再加吡啶的办法脱去羟基,再使用氢氧化钠来进行水解反应,酸化后得到固体(R)-环己烯基苯乙醇酸(Ⅳ),此步收率为55.2%。重结晶后的产品溶于甲醇中,用10%的钯-碳作为加氢催化剂进行加氢反应,得到纯品R-(-)-α-环己基扁桃酸,收率为61.2%,光学纯度为81.1%。

The raw materials of the asymmetric synthesis of R-（-）-α-cyclohexyl-mandelic acid（R-（-）-CHPGA）are R-（-）-mandelic acid and iso-butyraldehyde.The product of the first reaction step is cis-（2R,5R）-2-isopropyl-5-phenyl-1,3-dioxolan-4-one（Ⅰ）.The yield is 87.2%.Followed by the addition of cyclohexanone as electrophilic agent.Then,the reaction solution is added thionyl chloride（SOCl2）,followed by pyridine to dehydroxide.Next,NaOH is added to hydrolyze.After acidification,white solid is precipitated.It is R-cyclohex-1-enyl-hydroxy-phenyl-acetic acid（Ⅳ）.The yield is 55.2%.After recrystallization,the white solid is dissolved in methanol,followed by the addition of 10%Pd/C to hydrogenation.The purity R-（-）-CHPGA is gotten.The yield and the optical purity are 61.2%and 81.1%.