Electroreductive Cyclization Reactions in Organic Synthesis (Chemistry)

这个研究电化学技术在有机合成中的应用的项目得到了有机和大分子化学项目的支持。含有两个或多个远端官能团的线性分子被电解以在一个位置产生一个自由基阴离子，该阴离子将在另一个官能团上通过碳-碳键形成反应，从而形成含环化合物。本研究的中心是试图了解控制环化过程的各种因素。正在详细研究电还原环化反应，特别强调审查下列项目：a . 1。位于链上“战略重要位置”的取代基是否可以用作立体控制元素，从而允许对相对和绝对立体化学进行调节？2. 是否可以使用质子供体替代物（例如，Me3SiCl）和/或俘获效应来促进环化，而牺牲偶尔伴随着涉及酮的电还原环化的不必要的C-C键氢化？3. 电还原环化是否可以使用底物进行，其中-，-不饱和酯单元系在酯（内酯），酸酐或酸卤化物上？4. 这些研究的结果可以用来设计和实现一个合理的合成重要的生物学和建筑有趣的磷酯？B.在电还原环化反应中是否可以使用维生素B12或钴胺肟等介质，如果可以，这些反应是否可以催化进行？这些研究的结果正被应用于针对bicyclo?5.3的模型研究。十一烷是许多天然产物的共通结构。C.最后，研究了电还原环化反应的合成效用，该反应涉及碳-碳三键（例如，炔酮和炔酸酯）与易于还原的丙二酸烷基烯或梅尔德拉姆酸亚基相连接的系统。这样，最初形成的α， β -不饱和羰基化合物对进行还原的条件应是惰性的，因此可用于进一步细化。目前正在进行更多的研究，重点是使用环丙基梅尔德拉姆酸亚基（一种螺酰基）。

This project dealing with the use of electrochemical techniques in organic synthesis is being supported by the Organic and Macromolecular Chemistry Program. Linear molecules containing two or more distal functional groups are being subjected to electrolysis to generate a radical anion at one site which will react by carbon-carbon bond formation at the other functional group resulting in the formation of ring-containing compounds. This research is centered on an attempt to understand the various factors which govern the cyclization process. Electroreductive cyclization reactions are being studied in detail with a special emphasis placed upon an examination of the following items: A. 1. Can substituents positioned at "strategically important locations" on the tether be used as stereocontrol elements allowing for the regulation of both relative and absolute stereochemistry? 2. Can proton donor surrogates (e.g., Me3SiCl) and/or captodative effects be used to facilitate cyclization at the expense of the unwanted C-C pi bond hydrogenation which occasionally accompanies electroreductive cyclizations involving ketones? 3. Can electroreductive cyclizations be conducted using a substrate wherein the alpha, beta-unsaturated ester unit is tethered to an ester (a lactone), an acid anhydride, or an acid halide? 4. Can the results of these investigations be used to design and implement a rational synthesis of the biologically important and architecturally interesting phorbol esters? B. Can mediators such as vitamin B12 or cobaloxime be used in electroreductive cyclization reactions and, if so, can the reactions be conducted catalytically? The results of these studies are being applied to model studies directed toward construction of bicyclo?5.3.O!undecane framework common to a host of natural products. C. Finally, the synthetic utility of electroreductive cyclization reactions involving systems containing the carbon-carbon triple bond (e.g., alkynones and alkynoates) linked to an easily reduced alkylidene malonate or an alkylidene Meldrum's acid subunit is being examined. In this way, the initially formed alpha, beta-unsaturated carbonyl compound should be inert to the conditions under which the reduction is conducted and will consequently be available for further elaboration. Additional studies focusing upon the use of a cyclopropyl Meldrum's acid subunit (a spiroacylal) are being carried out.