Stereoselective Synthesis of Cyclic Ethers

描述(由申请人提供)：本建议的目的是开发新的串联式铋催化的分子间和分子内醚化反应，用于构建不相邻和稠合的多环醚。铋催化的醚化反应表现出显著的催化活性和特殊的化学选择性，其中直接与羰基的加成并不竞争氧碳正离子的形成。铋催化剂是商业上可以买到的，价格低廉，无毒，使它们成为许多合成应用的理想选择。金属催化的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、令人兴奋的机会，为合成药理活性物质提供了新的机会。具体感兴趣的领域摘要如下： 串联立体选择性分子内和分子间醚化：该提案的第一部分将涉及发展串联的非对映选择性铋催化的醚化反应，通过对氧卡宾离子进行排序，以构建不相邻的四氢吡喃环。然后，这一方法将被应用于高效抗肿瘤药物亮氨酸内酯A的聚合性全合成。 稠合多环醚的环化和还原醚化：该提案的第二个方面详细说明了开发新的铋催化的一步环化反应以及用于构建多环醚的闭环复分解反应。我们还将研究暂时的硅系留合环易位反应和立体选择性铋催化还原醚化反应的优点，以及它随后在冈比亚酸A-D的DEFGH部分的应用。最后，我们将研究一系列铋催化的双还原醚化反应，用于构建直链稠合多环醚。

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.