Design and Development of 1,3-diaza-Claisen Rearrangements

在这个由化学部化学合成计划资助的项目中，佛蒙特大学的José Madalengoitia将研究1，3-二氮杂-Claisen重排作为合成胍化合物的新方法。 整个反应包括将叔烯丙基胺加成到碳二亚胺上，得到两性离子中间体，该中间体又经历1，3-二氮杂-克莱森重排。 该项目的目标是1）确定最佳碳二亚胺反应性，然后探索扩环和分子内重排中的最佳碳二亚胺，2）开发通过阳离子中间体而不是两性离子中间体进行的重排，3）开发钯催化的重排，以及4）开发立体选择性形成新的立体中心的重排。 更广泛的影响涉及有机合成领域的研究生和本科生的培训。 此外，高中学生与项目种子合作将在夏季PI的实验室培训。 胍化合物是重要的，因为它们已被用作许多反应的催化剂，并且已报道胍衍生物具有一系列生物活性，包括抗菌和抗HIV活性。 这项工作将扩大胍化合物的制备方法，并将拓宽易于制备的胍化合物的范围。 本工作在合成胍类催化剂、胍类天然产物和胍类药物中的应用具有一定的社会效益。

In this project funded by the Chemical Synthesis Program of the Chemistry Division, José Madalengoitia of the University of Vermont will investigate the 1,3-diaza-Claisen rearrangement as novel method for the synthesis of guanidine compounds. The overall reaction involves the addition of a tertiary allylic amine to a carbodiimide to afford a zwitterionic intermediate that in turn undergoes a 1,3-diaza-Claisen rearrangement. The goals for this project are 1) to determine the optimal carbodiimide reactivity and to then explore optimal carbodiimides in ring expanding and intramolecular rearrangements, 2) to develop a rearrangement that proceeds through a cationic intermediate instead of a zwitterionic intermediate, 3) to develop a palladium-catalyzed rearrangement, and 4) to develop rearrangements in which a new stereocenter is formed stereoselectively. The broader impacts involve the training of graduate and undergraduate students in the area of organic synthesis. In addition, high school students in collaboration with Project SEED will be trained the PI's lab during the summer. Guanidine compounds are important as they have been used as catalysts for a number of reactions and guanidine derivatives have been reported to have a range of biological activities including anti-bacterial and anti-HIV activities. This work will expand the ways in which guanidine compounds can be made and will broaden the range of guanidine compounds that can be easily made. Societal benefits should come from the application of this work to the synthesis guanidine catalysts, guanidine natural products and guanidine pharmaceuticals.