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，用于构建非相邻和稠合的多环醚。铋催化的醚化反应表现出显着的催化活性和不寻常的化学选择性，其中羰基的直接加成不与氧碳正离子的形成竞争。铋催化剂是商业上可获得的，廉价且无毒，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机会，合成的药物活性剂。具体关注领域概述如下： 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串联非对映选择性铋催化醚化反应的开发，通过氧碳正离子的测序，用于构建非相邻的四氢吡喃环。然后将该方法应用于有效的抗肿瘤剂白藜芦醇内酯A的收敛全合成。 稠合多环醚的成环和还原醚化：提案的第二个方面详细介绍了新的铋催化一步成环反应与闭环复分解相结合用于构建多环醚的开发。我们还将研究的优点，临时硅系闭环复分解，然后由立体选择性铋催化还原醚化，其随后的应用程序的DEFGH部分的冈比亚酸A-D。最后，我们将研究一系列铋催化的双还原醚化反应，以构建线性稠合多环醚。

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.