RUI: New approaches to the synthesis of 1-benzoxocanes

本项目研究了1-苯并恶辛烷的一般合成方法。几个互补的策略，包括C-O和C-C成键反应，将继续进行。使用体积较大的Lewis酸催化剂，苯酚亲核试剂在环氧化物取代位置上的8位环化将被探索，构象约束和环化底物中的电子偏置有利于环化而不是环氧化物重排。另外，还将探索金属催化的过程，包括通过pd催化的瓦克型环化或通过用亲电试剂[PhSeX， Hg(II), I+, Ag(I), Au(I), Ru（III）和Ir(III)]激活烯，在拴链烯烃上添加苯酚亲核试剂，分子内pd催化的芳基三酸酯和叔烷醇之间的醚化反应，分子内拴链烯烃的芳基化[硅烷端端Heck反应，Ru(III), I+]，烯（Heck反应），或环氧化物[Au(III)]。有了这个RUI奖，有机和大分子化学项目支持了西华盛顿大学化学系James R. Vyvyan教授的研究。中型环状化合物在有机化学中占有特殊的地位，因为它们存在于生物活性化合物中，并给合成化学家带来了挑战。Vyvyan教授和他的学生正在探索各种新的策略，以有效合成1-苯并恶烷，8元环醚与含氧芳香环融合。在这个项目中开发的合成方法将是有价值的工具，用于制备有潜力作为农用化学品（向日葵醇）和药物先导（向日葵烷）的化合物。该项目是模块化的，使用几个关键的环化底物，以类似的方法组装，以测试许多不同的环化试剂和反应条件。这种模块化的性质允许每个学生研究人员都有自己的项目，并且仍然为合成含苯并恶烷的天然产物如heliannuols和heliananes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.