Organoiron Complexes in Organic Synthesis

该项目将继续研究在首席研究员的实验室中发现的涉及有机铁络合物的新反应的开发和应用。具体地说，将研究与铁三羰基络合的二烯和烯烃之间的环偶联反应的范围，即形式的[6+2]烯反应。这种反应类型是铁三羰基络合物所特有的，需要有机金属基团的化学计量使用，以防止分子内竞争的Diels-Alder反应。以串联方式进行的不对称双烯反应的应用将被探索为化学合成18-脱氧细胞松弛素H的一种方法，18-脱氧细胞松弛素H是一种感兴趣的HIV蛋白酶抑制剂。还将研究这种[6+2]烯反应的变体，在该反应中，侧链烯烃被醛和亚胺官能团取代，这扩大了该过程的范围。将串联的烯烃/醛[6+2]烯反应应用于麦哲伦酮的化学合成，这是一种结构复杂的石松生物碱天然产物，将是未来的长期目标。有了这个奖项，有机和高分子化学计划将支持凯斯西储大学化学系的安东尼·J·皮尔森教授的研究。皮尔逊教授的研究工作围绕着金属介导的反应的发展，以形成C-C键。这种化学将有助于环境友好的化学合成方法，因为随时可以获得的铁被用作中介关键反应的活性金属。该方法的成功开发将对制药和农业中的合成产生影响。

This project will continue research on the development and applications of new reactions involving organoiron complexes discovered in the Principal Investigator's laboratory. Specifically, the scope of cyclocoupling reactions between a diene complexed with an iron tricarbonyl group and an alkene, the formal [6+2] ene reactions, will be studied. This reaction type is unique to iron tricarbonyl complexes and requires the stoichiometric use of the organometallic group to prevent competing intramolecular Diels-Alder reactions. The application of an asymmetric double version of this ene reaction, carried out in a tandem manner, will be explored as an approach to the chemical synthesis of 18-deoxycytochalasin H, which is of interest as an HIV protease inhibitor. A variant of this [6+2] ene reaction in which the pendant alkene is replaced by aldehyde and imine functionality, which broadens the scope of the process, will also be studied. Application of tandem alkene/aldehyde [6+2] ene reactions to the chemical synthesis of magellaninone, a structurally complex lycopodium alkaloid natural product, will be pursued as a long term future goal.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Anthony J. Pearson of the Department of Chemistry at Case Western Reserve University. Professor Pearson's research efforts revolve around the development of metal-mediated reactions for the formation of C-C bonds. Such chemistry will contribute to environmentally benign methods for chemical synthesis as the readily available iron is used as the active metal that mediates the key reactions. Successful development of the methodology will have an impact on synthesis in the pharmaceutical and agricultural industries.