Synthetic studies employing a highly active palladium catalyst

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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.