Synthetic studies employing a highly active palladium catalyst

通过将Pd（Ac）_2或Pd（acac）_2与1当量的Bu_3P混合，制备了一种高活性的钯催化剂Pd（0）/Bu_3PO，该催化剂可有效地从低活性的烯丙基底物生成π-烯丙基钯配合物。我们设想了将钯催化氢解反应应用到维生素D_3的全合成中，以构建一些关键中间体。根据图1所示的逆合成，分子1被分成三个片段，如虚线a和B所示。2中的乙酰基被认为是一个多用途的取代基，可以通过钯催化的反应以及其他反应引入各种侧链。此外，2中的羟甲基附属物可以被修饰以连接到A环单元如3。因此，2具有合适的官能度和所需的绝对构型，是合成1的一个非常有前途的新型中间体。以1，3-环戊二酮衍生物4为原料，经不对称环化Horner-Emmons烯化反应得到关键中间体5（98%de）。最初的尝试集中在通过一系列反应将5中的C-1酮基转化为乙酰基部分，包括Pd催化的氢解作为关键步骤。

A highly active palladium catalyst, Pd(0)/Bu_3PO,has been created simply by mixing Pd(OAc)_2 or Pd(acac)_2 with one equivalent of Bu_3P.The new catalyst is highly effective for the generation of pi-allylapalladium complexes from less reactive allylic substrates. We have envisioned the total synthesis of vitamin D_3 by applying the palladium-catalyzed hydrogenolysis to the construction of some key intermediates. According to the retrosynthesis depicted in Figure 1, the molecule 1 is divided into three fragments as indicated by dotted lines a and b. The acety1 group in 2 is accepted as a versatile substituent to introduce varioud side chains by Pd-catalyzed reactions as well as others. In addition, the hydroxymethy1 appendage in 2 could be modified for connection to an A-ring unit such as 3. In this sense, 2, which possesses both the proper functionalities and the desired absolute configuration, appeared to be a very promising and novel intermediate for the synthesis of 1.The key intermediate 5 (98% de) was prepared from 1,3-cyclopentanedione derivative 4 via asymmetric cyclization by Horner-Emmons olefination. Initial attempts focused on the conversion of the C-1 keto group in 5 into an acety1 moiety by a sequence of reactions including Pd-catalyzed hydrogenolysis as a key step.