Stereoselective Synthesis of Cyclic Ethers

描述（由申请人提供）：本提案的目的是开发新的串联铋催化的分子间和分子内醚化反应，用于构建非相邻和熔融多环醚。铋催化的醚化反应表现出显著的催化活性和不同寻常的化学选择性，其中羰基的直接加成不与氧羰基离子的形成竞争。铋催化剂是市售的，便宜且无毒，使其成为许多合成应用的理想选择。金属催化多组分反应的发展为快速构建复杂的多环骨架提供了新的和令人兴奋的药物活性物质的合成机会。有关的具体领域总结如下：

DESCRIPTION (provided by applicant): The aim of this proposal is the development of new tandem bismuth-catalyzed inter- and intramolecular etherification reactions for the construction of non-adjacent and fused polycyclic ethers. The bismuth-catalyzed etherification reactions exhibit remarkable catalytic activity and unusual chemoselectivity, in which the direct addition to the carbonyl does not compete with the formation of the oxocarbenium ion. The bismuth catalysts are commercially availabile, inexpensive and non-toxic, making them ideal for many synthetic applications. The development of metal-catalyzed multi-component reactions for the rapid construction of complex polycyclic skeletons provides new and exciting opportunities for the synthesis of pharmacologically active agents. The specific areas of interest are summarized as follows: Tandem Stereoselective Intra- and Intermolecular Etherifications: The first section of the proposal will involve the development of tandem diastereoselective bismuth-catalyzed etherification reactions, through the sequencing of oxocarbenium ions, for the construction of non-adjacent tetrahydropyran rings. This methodology will then be applied to a convergent total synthesis of the potent antitumor agent leucascandrolide A. Annulation and Reductive Etherifications for Fused Polycyclic Ethers: The second aspect of the proposal details the development of new bismuth-catalyzed one-step annulation reactions in combination with ring-closing metathesis for the construction of polycyclic ethers. We will also examine the merit of temporary silicon-tethered ring-closing metathesis followed by the stereoselective bismuth-catalyzed reductive etherification, and its subsequent application to the DEFGH portion of the gambieric acids A-D. Finally, we will examine a series bismuth-catalyzed bis-reductive etherification reactions for the construction of linear fused polycyclic ethers.