手性香料化合物γ-内酯的不对称合成

Asymmetric synthesis of chiral aroma compounds γ-lactones

以丙二酸和脂肪醛为起始原料,通过Knoevenagel缩合、酯化、Sharpless不对称双羟基化、消除和还原五步反应制备了一系列光学活性的γ-内酯。首先丙二酸与脂肪醛在哌啶的催化作用下得到(E)-3-烷烯羧酸,产率70%左右;(E)-3-烷烯羧酸转化为甲酯后,用Sharpless不对称双羟基化试剂AD-mix-α或AD-mix-β氧化,得到光学活性的3-羟基-4-烷基-γ-内酯,双羟基化反应产率85%左右;将3-羟基-4-烷基-γ-内酯的羟基转化为甲磺酸酯后,通过消除反应,得到光学活性的4-烷基-α,β-不饱和-γ-内酯,产率80%左右;然后用Pd/C催化加氢还原,得到光学活性的4-烷基-γ-内酯,产率90%左右。所有产物的结构都通过1HNMR或GC-MS进行了确认,最终产物的对映体过量(ee)值通过手性GC进行了测定。

A series of optically active γ-lactones were prepared starting with malonic acid and aliphatic aldehydes through Knoevenagel condensation,esterification,Sharpless asymmetric dihydroxylation,elimination and reduction.The way of synthesis was as follows：malonic acid reacted with aliphatic aldehydes catalyzed by piperidine to get intermediates Ⅰ [（E）-3-alkenoic acids] with yield of about 70%;the intermediates Ⅰesterified with methanol to get intermediates Ⅱ;the intermediates Ⅱ reacted with Sharpless asymmetric dihydroxylation reagent AD-mix-α or AD-mix-β to get intermediates Ⅲ（optically active 3-hydroxy-4-alkyl-γ-lactones） with yield of about 85%;the intermediates Ⅲ reacted with methylsulfonyl chloride,followed by elimination of the sulfonyl group to get intermediates Ⅳ（optically active 4-alkyl-α,β-unsaturated γ-lactones） with yield of about 80%;the intermediates Ⅳ hydrogenated under the catalyst Pd/C to get the products Ⅴ（optically active γ-lactones） with yield of about 90%.The structures of products were characterized by 1HNMR and/or GC-MS.The ee values of the final products were determined by chiral GC.