Development of the Highly Efficient Methodology for the Construction of Medium-sized Cyclic Ethers and its Application to Polycyclic Ether Compounds.

1.中尺寸环醚结构催化体系和循环系统的开发本论文研究了以Eu(Fod)_3为催化剂的羟基环氧化物的环化反应，用于中尺寸环醚的合成。为了从原子经济的角度发展成为有效的方法学，对方法学的催化体系和循环系统进行了考察。为此，使用了离子液体/有机溶剂和氟溶剂/有机溶剂体系。在此条件下，催化量的Lewis酸有望被浓缩并加速反应。然而，这些尝试都被证明是徒劳的。对反应的Lewis酸的测定表明，Y(HFA)_3是一种有效的Lewis酸，尽管它不适用于催化用途。高效立体选择性构筑多环醚骨架的方法学研究用上述方法…考察了多环醚骨架的立体选择性构筑更多的对数1)7元环醚的扩展：包括环氧基团的膦酸酯被设置为手性合成子。用试剂进行的一系列Horner-Emmons类型的反应，由邻近环氧基的立体化学引起的羰基的反选择性还原，提供了所需的羟基和环氧基的立体化学前驱体。用Eu(Fod)_3连续环化得到7元环醚扩展产物。2)8元和9元环醚的扩展：(+)-甘露醇衍生的手性二环氧化物被设定为手性合成子。采用山口的方法在二环氧化物中加入炔基阴离子，得到具有所需的羟基和环氧基立体化学的前体。用Y(HFA)_3连续环合得到8元和9元环醚扩展产物。如上所述，建立了用于合成多环醚的7元、8元和9元环醚体系的扩展。多环醚类化合物的合成研究将上述方法应用于多环醚类化合物的合成。成功地合成了半短杆菌毒素B的BCD环和雪卡毒素3C的7，8环。较少

1. Development of a catalytic and a recycle system of the medium-sized cyclic ethers constructionWe disclosed cyclization of hydroxy epoxides by use Eu(fod)_3 for the construction of medium-sized cyclic ethers. In order to develop into the efficient methodology from the point of view of an atomic economy, a catalytic and a recycle system of the methodology were examined. For these purposes, ionic liquid/organic solvent and fluorous solvent/organic solvent system were used. A catalytic amount of Lewis acid was expected to be concentrated under the conditions and accelerate the reaction. However, these attempts proved fruitless. Surveying of Lewis acid for the reaction revealed Y(hfa)_3 is an efficient Lewis acid, although it was not applicable to a catalytic use.2. Development of the methodology for the highly efficient and stereoselective construction of the polycyclic ether skeletonStereoselective construction of polycyclic ether skeleton was examined using the above mentioned methodo … More logy.1) Extension of the 7-membered cyclic ether : The phosphonate including an epoxy moiety was set as a chiral synthon. A sequence of Horner-Emmons type reaction using the reagent, anti-selective reduction of the carbonyl group induced by stereochemistry of the neighboring epoxy group provided a precursor with required stereochemistry of hydroxy and epoxy groups. Successive cyclization by use of Eu(fod)_3 gave the 7-membered cyclic ether-extended product.2) Extension of the 8- and 9-membered cyclic ethers : The chiral diepoxide derived from (+)-mannitol was set as a chiral synthon for these purposes. Addition of alkynic anion to the diepoxide applying the Yamaguchi's protocol afforded a precursor with required stereochemistry of hydroxy and epoxy groups. Successive cyclization by use of Y(hfa)_3 gave the 8- and 9-membered cyclic ether-extended product. As described above, extension of 7-, 8-, and 9-memberd cyclic ether systems for the synthesis of polycyclic ethers was established.3. Synthetic study of polycyclic ether compoundsThe above methodology was applied to synthesis of polycyclic ether compounds. The BCD-ring, the 6,6,7-fused ring system, of hemibrevetoxin B and the DE-ring, the 7,8-ring system, of ciguatoxin 3C were successfully synthesized. Less