Palladium-Catalyzed Transient Directing Group-Enabled Functionalization of Aliphatic Amines and Aldehydes

化学学部化学合成项目支持美国印第安纳大学-普渡大学化学与化学生物系葛海波教授的项目。胺是由氨通过一个或多个氢原子被有机基团取代而衍生的有机化合物。胺在生物学中非常常见，比如氨基酸和神经递质，包括肾上腺素、去甲肾上腺素、多巴胺、血清素和组胺。这项研究的目的是将简单的胺转化为其他更有价值或有用的胺。为了解决这一挑战，葛教授和他的学生们正在使用“导向基团”，它可逆地附着在胺基上，迫使反应在特定的（期望的）位点上发生。夏季本科生研究项目吸引了大学生，尤其是女性和少数族裔，进入STEM领域，培养潜在的未来科学研究领导者。高中教师的参与提供了一个积极的学习环境，使他们能够将关键科学思想和实践的深入知识传授给他们的课堂。这种教育的努力，反过来又激发了高中生的好奇心，激发了他们对化学的兴趣，吸引了更多的高中生进入STEM领域。该项目由印第安纳大学-普渡大学印第安纳波利斯分校（IUPUI）化学与化学生物学系的葛海波教授主持，由化学学部化学合成项目资助。葛教授正在开发构建碳碳和碳杂原子键的新方法。这种反应化学允许各种常见的有机化合物很容易地通过C-H键功能化过程有效地获得。它还可以实现复杂有机分子的快速后期功能化（LSF）。与传统的交叉偶联反应相比，C-H功能化过程不需要预功能化的起始材料，并且可以避免使用化学计量的有机金属试剂，使其更具环保和经济效益。新型C-H功能化反应允许使用易于获得的有机分子作为起始材料，从而提高了该工艺的潜在应用。该项目的主要目标是开发新的过渡金属催化的碳氢功能化反应，以提供强大的，有价值的，直接的合成方法来获取常见的有机框架。各种医学上重要的（杂）环骨架有望通过这种策略从现成的脂肪胺和醛中有效地获取。用手性催化剂设计了这些强sp3碳-氢键的不对称功能化。该项目主要侧重于合成有机化学和有机金属化学，并可能整合计算化学和药物化学。因此，该项目为各级科学家的教育和培训奠定了良好的基础。此外，还有一个针对高中教师的拓展项目，旨在使他们能够将关键科学思想和实践的深入知识传授给他们的课堂。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor Haibo Ge of the Department of Chemistry and Chemical Biology at Indiana University-Purdue University. Amines are organic compounds derived from ammonia by replacement of one or more hydrogen atoms by organic groups. Amines are very common in biology such as in amino acids and neurotransmitters including epinephrine, norepinephrine, dopamine, serotonin, and histamine. The goal of this research is to convert simple amines into other, more valuable or useful amines. To solve this challenge, Professor Ge and his students are using "directing groups" that attach reversibly to the amine group and force the reaction to occur on a specific (desired) site. The summer undergraduate research program attracts college students, especially women and underrepresented minorities, to the STEM areas, training potential future leaders in scientific research. The engagement of high school teachers provides an active learning environment and enables them to deliver in-depth knowledge of key scientific ideas and practices to their classes. This educational effort, in turn, triggers high school students' curiosity, inspires their interest in chemistry, and attracts more high school students into the STEM areas.The Chemical Synthesis Program of the Chemistry Division supports the project by Professor Haibo Ge of the Department of Chemistry and Chemical Biology at Indiana University-Purdue University Indianapolis (IUPUI). Professor Ge is developing new methods to construct carbon-carbon and carbon-heteroatom bonds. This reaction chemistry allows for various common organic compounds to be readily accessed in an efficient manner via a C-H bond functionalization process. It also enables rapid late-stage functionalization (LSF) of complex organic molecules. When compared to conventional cross-coupling reactions, the C-H functionalization process does not require pre-functionalized starting materials and can avoid the use of stoichiometric organometallic reagents, making it more environmentally and economically beneficial. The new type of C-H functionalization reactions allows for the use of readily-available organic molecules as starting materials, and thus improves the potential applications of the process. The principal goal of the project is to develop novel transition metal-catalyzed C-H functionalization reactions in order to provide powerful, valuable, and straightforward synthetic approaches to access common organic frameworks. A variety of medically important (hetero)cyclic skeletons are expected to be efficiently accessed from readily-available aliphatic amines and aldehydes via this strategy. The asymmetric functionalization of these strong sp3 C-H bonds is also designed with the use of chiral catalysts. The project focuses primarily on synthetic organic and organometallic chemistry with potential integration of computational and medicinal chemistry. Thus, the project is well-positioned for the education and training of all levels of scientists. Additionally, an outreach program with high school teachers is designed to enable them to deliver in-depth knowledge of key scientific ideas and practices to their classes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.