Study Onasymmetric Syntheses Of 3-methylthio Hexanal And 5 Or 6-butyl-1, 4-dioxan-2-one

The preparation of optically active 3-methylthio aldehyde, 5(6)-butyl-1, 4- dioxan-2-one and 2-methyl-3-mercapto pentanal was studied by the Sharpless AE.The optically active 3-methylthio hexanal was prepared starting from E-2-hexenal through reduction of aldehyde, the Sharpless AE, the reduction of epoxide, nucleophilic substitution and Swern Oxidation etc. The chemical yields in this route generally reached about 75% except the Sharpless AE with about 65% yield. The conditions of the Sharpless AE were optimized by experiments. The optimum conditions were as follows: temperature -25oC, n(Ti(Oi-Pr)₄) / n(E-2-hexenal) = 10%, n(t-BuOOH) / n(E-2-hexenal) = 2:1. The reaction gave the product in about 65% yield with 93% ee under these conditions.The optically active 2, 3-epoxy hexanol was regioselectively reduced by DIBAL-H to give optically active 1, 2-hexanediol in about 72% yield. 5(6)-Butyl-1, 4-dioxan -2-one was prepared by the reaction of 1, 2-hexanediol withα-bromo acetic chloride. The ratio of 6-Butyl-1, 4-dioxan-2-one to 5-Butyl-1, 4-dioxan-2-one was about 4/1. The total yield of two prodcuts was about 71%.The enantiomeric excesses (ee) of optically active 3-methylthio hexanal and 5(6)-butyl-1, 4-dioxan-2-one were determined by chiral GC respectively. The results were as follows: (S)-3-methylthio hexanal with 90.8% ee, (R)-3-methylthio hexanal with 91.1% ee, (R)- and (S)- 5(6)-butyl-1, 4-dioxan-2-one with about 90% ee. The method gave optically active 3-methylthio hexanal and 5(6)-butyl-1, 4-dioxan-2-one with high ee in mediate to high chemical yields by using the Sharpless AE. So it is an ideal route to prepare optically active 3-methylthio hexanal and 5(6)-butyl-1, 4-dioxan-2-one.The preparation of optically active 2-methyl-3-mercapto pentanal was tried by using the method analogous to synthesizing optically active 3-methylthio hexanal. With 2-methyl pentenoic acid as the starting material, through the reduction of carboxyl group and the Sharpless AE, optically active 2-methyl-2, 3-epoxy pentanol was obtained. But 2-methyl-2, 3-epoxy pentanol was reduced by Red-Al to give 1, 2-diol, not the desired 1, 3-diol. So it failed to prepare optically active 2-methyl-3-mercapo pentanal. It will need further investigation to prepare optically active 2-methyl-3-mercapo pentanal.