Advances in (4+3)-Cycloaddition Chemistry

在这个由化学系化学合成计划资助的项目中，密苏里-哥伦比亚大学化学系的Michael Harmata教授将探索在温和条件下产生烯丙基阳离子的方法，并研究它们与双烯的[4+3]-环加成反应。在双烯存在的情况下，将制备硅氧基丙烯醛，并与催化量的手性Lewis酸反应。这类研究也将用这些物种的原木进行。氯酮和各种衍生物将在二烯存在下与手性胺碱进行处理，以期生成与手性反离子键合的氧烯丙基阳离子，从而在随后的反应中诱导立体选择性。手性非亲核阴离子的银盐将被类似地使用，手性硫脲与氯酮衍生物也将被使用。最后，将发展某些烯丙醇衍生物的光致电离和金催化从选定的烯丙醇酯中生成烯丙基阳离子。[4+3]-环加成反应直接导致合成七元环，这是一种具有重要生物学意义的化合物的亚结构。此外，Harmata小组和其他人的研究表明，这种反应可以导致不同的环大小，增加简单起始材料的分子复杂性，以经济的方式生产增值结构。这项工作的成功成果将对制药、农用化学品和特种化学品行业产生积极影响。此外，该项目将为学生提供极好的培训，包括那些在科学界历来代表性不足的学生。

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Michael Harmata of the Department of Chemistry at the University of Missouri-Columbia will explore the development of methods for the generation of allylic cations under mild conditions and study their [4+3]-cycloadditions with dienes. Silyloxyacroleins will be prepared and treated with catalytic amounts of chiral Lewis acids in the presence of dienes. Such studies will also be conducted with vinylogs of these species. Chloroketones and various derivatives will be treated with chiral amine bases in the presence of dienes in anticipation of the generation of oxyallylic cations bonded to chiral counterions able to induce stereoselectivity in subsequent reactions. Silver salts of chiral non-nucleophilic anions will be used similarly, as will chiral thioureas with chloroketone derivatives. Finally, the photoionization of certain derivatives of allylic alcohols and the gold-catalyzed generation of allylic cations from selected esters of allylic alcohols will be developed. The [4+3]-cycloaddition reaction results directly in the synthesis of seven-membered rings, a substructure of a vast number of compounds that are biologically important. Further, studies from the Harmata group and others have demonstrated that this reaction can lead to a variety of ring sizes, increasing molecular complexity of simple starting materials in short order to produced value-added structures economically. The successful results of this work could positively impact the pharmaceutical, agrochemical and specialty chemical industries. In addition, this project will provide excellent training of students, including those from groups historically underrepresented in the sciences.