Novel Methods for the Synthesis of Nitrogen Heterocycles

在化学系化学合成计划的支持下，北卡罗来纳州立大学罗利分校的约书亚·G·皮尔斯正在研究制备一类重要的含氮杂环天然产物支架的新方法。具体地说，感兴趣的目标包含五元含氮环，正在开发的各种获得它们的方法都有一个共同的主题，即通过在三原子组分的基础上添加两原子组分来构建环。除了这项研究承诺的有机合成领域的基本进展外，它还将提供获得对医学、农业和材料科学有价值的复杂分子的新方法。随着皮尔斯研究团队参与各种公共宣传活动，包括北卡罗来纳州罗利市自然科学博物馆的成人活动和当地一所小学的儿童活动，该资助项目的更广泛影响将延伸到为社会带来的好处。这些活动，除了通过项目SEED机构提供身临其境的实验室体验外，还将促进社区中的STEM(科学、技术、工程和数学)教育，同时也有助于扩大来自未被充分代表的群体的个人对科学的参与。本研究项目旨在利用形式[3+2]-环加成逻辑以立体选择性的方式制备密集功能化的杂环支架，并扩大底物范围和对符合这一范例的过程的机械理解。目前正在研究的三个领域是：(1)带有新型偶极的联烯(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)3-氮杂双环[3.2.1]辛烷衍生物的光氧化还原合成；(3)通过三组分的形式[3+2]-环加成反应选择性地合成吡咯-2-酮支架，并随后将其转化为增值产品。正在进行的次级项目通过逆合成断开联系起来，设想相关的杂环目标从三原子和两原子合成子中出现，每个次级项目都由独特的反应性战略实现。正在进行的所有三种方法都旨在克服合成氮杂环的现有限制，预计这项工作将导致对基本反应性的更好理解，并产生更广泛适用于其他类型杂环精制的结果。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.