RUI: New approaches to the synthesis of 1-benzoxocanes

本项目致力于开发合成1-苯并辛烷的通用合成方法。将采取几种补充策略，既涉及C-O反应，也涉及C-C键形成反应。在大型Lewis酸催化剂的作用下，苯酚亲核试剂发生8-内环化反应，环化底物上的构象限制和电子偏向有利于环化反应而不是环氧化物重排。或者，还将探索金属催化的过程，包括通过钯催化的瓦克型环化或通过亲电试剂[PhSeX，Hg(II)，I+，Ag(I)，Au(I)，Ru(III)和Ir(III)]激活烯烃，分子内Pd催化的三氟芳基与叔烷氧烷之间的醚化，以及链烯的分子内芳基化[硅烷终止的Heck反应，Ru(III)，I+]，烯(Heck反应)，或环氧化物[Au(III)]。有机和高分子化学项目正在支持西华盛顿大学化学系教授詹姆斯·R·维维扬的研究。中等尺寸的环状化合物在有机化学中占有特殊的地位，因为它们存在于具有生物活性的化合物中，并对合成化学家提出了挑战。Vyvyan教授和他的学生正在探索各种新的策略，以有效地合成1-苯并氧杂环辛烷，8元环醚融合到一个含氧芳环。该项目将开发的合成方法将是制备有潜力作为农用化学品(向日葵醇类)和药物先导化合物(向日葵)的有价值的工具。该项目是模块化的，使用几个以类似方法组装的关键环化底物来测试许多不同的环化试剂和反应条件。这种模块化的性质使每个学生研究人员都可以有自己的项目，并仍然为合成含有苯并氧杂环己烷的天然产品(如向日葵和向日葵)的长期目标做出有意义的贡献。

This project addresses the development of general synthetic methods for the construction of 1-benzoxocanes. Several complementary strategies, involving both C-O and C-C bond-forming reactions, will be pursued. An 8-endo cyclization of a phenol nucleophile onto the more substituted position of an epoxide using bulky Lewis acid catalysts will be explored, with conformational constraints and electronic bias in the cyclization substrate favoring cyclization over epoxide rearrangement. Alternately, metal-catalyzed processes will be explored, including addition of a phenol nucleophile to a tethered alkene by Pd-catalyzed Wacker-type cyclization or by activating the alkene with electrophiles [PhSeX, Hg(II), I+, Ag(I), Au(I), Ru(III) and Ir(III)], intramolecular Pd-catalyzed etherification between an aryl triflate and a tertiary alkoxide, and intramolecular arylation of a tethered alkene [silane-terminated Heck reaction, Ru(III), I+], allene (Heck reaction), or epoxide [Au(III)].With this RUI award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor James R. Vyvyan, of the Department of Chemistry at Western Washington University. Medium-sized ring compounds hold a special place in organic chemistry due to their presence in biologically active compounds and the challenge they present to the synthetic chemist. Professor Vyvyan and his students are exploring a variety of new strategies for the efficient synthesis of 1-benzoxocanes, 8-membered ring ethers fused to an oxygenated aromatic ring. The synthetic methods to be developed in this project will be valuable tools for the preparation of compounds that have potential as agrochemicals (heliannuols) and as drug leads (heliananes). The project is modular, using a few key cyclization substrates assembled by similar methods to test many different cyclization reagents and reaction conditions. This modular nature allows each student researcher to have their own project, and still make meaningful contributions to the long-range goal of synthesizing benzoxocane-containing natural products like the heliannuols and heliananes.