SusChEM: Copper-Catalyzed Radical Reactions of Nitroso Compounds for the Synthesis of Carbon-Nitrogen Bonds

化学部的化学催化方案支持里德·德·阿拉尼兹教授的项目。里德·德·阿拉尼斯教授是加州大学圣巴巴拉分校化学系的教员。他正在开发新的策略，利用地球上丰富的金属将氮和氧原子直接结合到结构不同的分子中。这项研究的目标是开发一种通用和通用的策略，以加快治疗药物的发现。含氮治疗剂的分子多样性和含氮取代基对药代动力学和药效学的强烈影响要求开发新的方法将这些官能团安装到治疗性有机小分子中。此外，该方法在材料科学以及构建农用化合物方面具有潜在的应用前景。该项目非常适合各级科学家的教育。该教育计划包括在UCSB加州纳米系统研究所和材料研究实验室(尤其是RISE、SIMS、UC Leads、CAMP和MARC计划)对未被充分代表的群体进行杰出的专业发展和研究培训计划，以及为研究生开发一个新的多层次指导计划。虽然胺的价值和自由基反应的合成效用是众所周知的，但通过将自由基反应与亚硝基化合物合并来构建碳(C)-氮(N)和碳-氧(O)键的策略几乎是完全未知的。通过这些研究，碳-氮键形成反应的新机会正在开发中，这些反应温和、官能团宽容，并使用地球上丰富的铜。这些新的转变减少了获得本来难以制备的含氮分子所需的合成步骤的数量。这些转变还使化学家有机会获得新的合成键断开。具体地说，拟议工作的目标是：1)扩大最近开发的铜催化的与亚硝基化合物的自由基加成反应的范围，包括杂环、苄基溴化物和α-溴腈；2)利用亚硝酸盐原位生成亚硝基试剂与商业上可获得的芳基和杂芳基三氟硼酸盐进行反应；3)将这一策略应用于简单的吡咯吲哚生物碱天然产物的全合成；4)开发一种新的基于分子内自由基的N-O转移过程，它提供了一系列结构上的氮和氧杂原子的空间控制。里德·德·阿拉尼兹教授的团队处于有利地位，可以为在科学领域代表性不足的学生提供最高水平的教育和培训。涉及新的多层次指导计划的外展活动是该项目的一部分。

The Chemical Catalysis Program of the Chemistry Division supports the project by Professor Read de Alaniz. Professor Read de Alaniz is a faculty member in the Department of Chemistry at University of California Santa Barbara (UCSB). He is developing new strategies for the direct incorporation of nitrogen and oxygen atoms into structurally diverse molecules using earth abundant metals. The goal of this research is to develop a general and versatile strategy to expedite the discovery of therapeutic agents. The molecular diversity of nitrogen containing therapeutic agents and the strong influence nitrogen substituents have on both pharmacokinetics and pharmacodynamics mandates the development of new methodologies for installing these functional groups into small therapeutic organic molecules. In addition, the methodology has potential applications in material science, as well as for the construct of agrochemical compounds. The project is well suited for the education of scientists at all levels. The educational plan includes training of underrepresented groups in outstanding professional development and research training programs at UCSB's California NanoSystems Institute and Materials Research Lab (notably the RISE, SIMS, UC LEADS, CAMP, and MARC programs), as well as developing a new multi-layered mentoring program for graduate students. While the value of amines and the synthetic utility of radical reactions are well-established, exploration of the strategy for constructing carbon (C) - nitrogen (N) and C-oxygen (O) bonds by merging radical reactions with nitroso compounds is almost completely unknown. Through these studies, new opportunities in C-N bond-forming reactions that are mild, functional group tolerant, and use earth abundant copper are under development. These new transformations reduce the number of synthetic steps required to access nitrogen containing molecules that are otherwise difficult to prepare. The transformations also give chemists access to new synthetic bond disconnections. Specifically, the goals of the proposed work are: 1) extend the scope of the recently developed copper-catalyzed radical addition with nitroso compounds to include heterocycles, benzyl bromides and alpha-bromo nitriles; 2) develop the reaction with commercially available aryl and heteroaryltrifluoroborates using nitrite salts to generate the nitroso reagent in situ; 3) apply this strategy to the concise total synthesis of pyrroloindoline alkaloid natural products; 4) develop a new intramolecular radical based N-O transfer process that provides spatial control of the nitrogen and oxygen heteroatoms over a range of architectures. Professor Read de Alaniz's group is well positioned to provide the highest level of education and training for students underrepresented in science. Outreach activities involving a new multi-layered mentoring program are part of the project.