Novel Methods for the Synthesis of Nitrogen Heterocycles

约书亚G.位于罗利的北卡罗来纳州州立大学的皮尔斯正在研究制备一类重要的以氮杂环为特征的天然产物支架的新方法。 具体而言，目标含有五元含氮环，并且正在开发的各种方法都有一个共同的主题，即通过将两个原子组分添加到三个原子组分来构建环。除了研究承诺的有机合成领域的根本性进展之外，它还将提供新的方法来获得对医学，农业和材料科学有价值的复杂分子。资助项目的更广泛的影响将扩展到社会的利益，因为皮尔斯研究团队参与各种公共宣传活动，包括在北卡罗来纳州罗利自然科学博物馆为成年人举办的活动，以及为当地小学的儿童举办的活动。这些活动，除了将通过SEED项目提供的沉浸式实验室体验外，还将促进STEM（科学、技术、工程和数学）教育，同时也有助于扩大科学代表性不足的群体的个人参与。该研究项目旨在利用正式的[3+2]-环加成逻辑，以立体选择性方式制备密集官能化的杂环支架，并扩大底物范围和符合该范例的过程的机理理解。三个重点领域正在调查中：（1）一个等位基因（或烯烃）/1，3-偶极环加成反应以构建螺环吡咯烷和/或内酰胺;（2）光氧化还原激活的3-氮杂双环[3.2.1]辛烷衍生物的合成;和，（3）通过三组分的吡咯-2-酮支架的对映选择性方法，形式[3+2]-环加成过程和随后转化为增值产品。正在进行的子项目是由一个逆合成断开，设想从三个和两个原子的合成子出现的相关杂环目标，每个是由一个独特的反应性策略。所有这三种方法都是为了克服氮杂环合成中的现有限制，预计这项工作将导致对基本反应性的更好理解，并导致更广泛地适用于其他类型杂环的制备的发现。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识产权进行评估来支持。优点和更广泛的影响审查标准。

With the support of the Chemical Synthesis Program in the Division of Chemistry, Joshua G. Pierce of North Carolina State University at Raleigh is studying new methods for the preparation of an important class of natural product scaffolds featuring nitrogen heterocycles. Specifically, the targets of interest contain five-membered nitrogen-containing rings and the varied range of methods being developed to access them all share a common theme of constructing the ring by adding a two-atom component to a three-atom component. Beyond the fundamental advances to the field of organic synthesis that the research promises, it will also provide new ways to access complex molecules of value to medicine, agriculture, and materials science. The broader impacts of the funded project will extend to the benefits accrued to society as the Pierce research team engages in various public outreach activities, including events for adults at the Natural Sciences Museum in Raleigh, NC, and for children at a local elementary school. These activities, in addition to immersive laboratory experiences that will be offered via the agency of Project SEED, will promote STEM (science, technology, engineering and mathematics) education in the community while also helping to broaden the participation of individuals from underrepresented groups in science.This research project aims to leverage formal [3+2]-cycloaddition logic to prepare densely functionalized heterocyclic scaffolds in a stereoselective fashion and to expand the substrate scope and mechanistic understanding of processes conforming to this paradigm. Three areas of focus are under investigation: (1) an allene (or alkene) / 1,3-dipolar cycloaddition with novel dipoles to construct spirocyclic pyrrolidines and/or lactams; (2) a photoredox-enabled synthesis of 3-azabicyclo[3.2.1]octane derivatives; and, (3) enantioselective approaches to pyrrol-2-one scaffolds via a three component, formal [3+2]-cycloaddition process and their subsequent conversion to value added products. The subprojects being pursued are united by a retrosynthetic disconnection that envisions the relevant heterocyclic target emerging from a three- and a two-atom synthon and each is enabled by a unique reactivity strategy. All three of the approaches being pursued are designed to overcome an existing limitation in the synthesis of azacycles and it is anticipated that this work with lead to an improved understanding of fundamental reactivity and to findings that are more broadly applicable to the elaboration of other types of heterocycles.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.