Hayashi Yujiro, Saitoh Takanobu, Arase Hiromu, Kawauchi Genki, Takeda Naohiro, Shimasaki Yasuharu, Sato Itaru
Department of Chemistry, Graduate School of Science, Tohoku University, 6-3 Aramaki-Aza Aoba, Aoba-ku, Sendai, 980-8578, Japan.
Present address: Department of Chemistry, Faculty of Science, Ibaraki University, Ibaraki, 310-8512, Japan.
Chemistry. 2018 Apr 3;24(19):4909-4915. doi: 10.1002/chem.201705930. Epub 2018 Mar 2.
A two-pot synthetic method to construct the chiral syn-1,3-diol unit has been developed from three aldehydes and either Wittig or Horner-Wadsworth-Emmons reagents. In the first pot, chiral δ-hydroxy α,β-unsaturated ketones are synthesized with excellent enantioselectivity by the organocatalyst-mediated asymmetric direct aldol reaction of two different aldehydes, followed by either Wittig or Horner-Wadsworth-Emmons reactions. In the second pot, domino acetalization with an aldehyde and subsequent oxy-Michael reaction proceeds in the presence of NaClO and a catalytic amount of Bi(OTf) (OTf=trifluoromethanesulfonate) to provide the chiral 1,3-syn-diol derivative with excellent diastereoselectivity. Diospongin C and yashabushidiol A have been synthesized efficiently by using the present method as a key step.
一种由三种醛与维蒂希试剂或霍纳尔-沃兹沃思-埃蒙斯试剂构建手性顺式-1,3-二醇单元的双锅合成方法已被开发出来。在第一锅中,通过有机催化剂介导的两种不同醛的不对称直接羟醛缩合反应,以优异的对映选择性合成手性δ-羟基α,β-不饱和酮,随后进行维蒂希反应或霍纳尔-沃兹沃思-埃蒙斯反应。在第二锅中,在次氯酸钠和催化量的三氟甲磺酸铋(OTf = 三氟甲磺酸盐)存在下,与醛进行多米诺缩醛化反应并随后进行氧迈克尔反应,以优异的非对映选择性提供手性1,3-顺式二醇衍生物。通过使用本方法作为关键步骤,已高效合成了海绵骨针素C和矢布士地醇A。