Electroreductive Cyclization Reactions in Organic Synthesis (Chemistry)

这项涉及在有机合成中使用电化学技术的项目得到了有机化学和高分子化学计划的支持。含有两个或两个以上远端官能团的线性分子被电解，在一个位置产生自由基阴离子，该阴离子将通过在另一个官能团形成碳-碳键而反应，从而形成含环化合物。这项研究的中心是试图了解控制环化过程的各种因素。对电还原环化反应进行了详细的研究，并特别强调了以下几点：a.位于系绳上“具有战略意义的位置”的取代基是否可以用作立体控制元件，以允许调节相对和绝对的立体化学？2.质子供体替代物(如Me3SiCl)和/或捕集效应能否被用来促进环化反应，而不是以不必要的C-C pi键氢化为代价，而不是偶尔伴随涉及酮类的电还原环化反应？3.电还原环化反应可以使用底物进行吗？在底物中，α，β-不饱和酯单元系于酯(内酯)、酸内酯、氢化物或者是酸性卤化物？4.这些研究的结果能用来设计和实现具有生物重要性和建筑意义的佛波酯的合理合成吗？B.介体如维生素B12或钴肟可以用于电还原环化反应吗？如果可以，这些反应能否在催化下进行？这些研究的结果正被应用于模型研究，旨在构建一系列天然产品所共有的双环5.3O！十一烷骨架。C.最后，正在研究电还原环化反应的合成用途，该反应涉及的体系中含有连接到容易还原的亚烷基丙二酸酯或亚烷基梅尔德鲁姆酸亚单位的碳-碳三键(例如，炔酮和烷基诺酸酯)。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该是惰性的，因此将可用于进一步的阐述。正在进行其他研究，重点是环丙基梅尔德鲁姆酸亚基(螺酰基)的用途。

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.