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

化学学部的化学催化项目支持Read de Alaniz教授的项目。Read de Alaniz教授是加州大学圣巴巴拉分校（UCSB）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多样的分子中。这项研究的目标是开发一种通用的、通用的策略来加速治疗药物的发现。含氮治疗剂的分子多样性和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小的治疗有机分子中。此外，该方法在材料科学以及农用化合物的构建方面具有潜在的应用前景。这个项目非常适合各级科学家的教育。该教育计划包括在UCSB的加州纳米系统研究所和材料研究实验室（特别是RISE、SIMS、UC LEADS、CAMP和MARC项目）对未被充分代表的群体进行优秀专业发展和研究培训项目的培训，以及为研究生开发一个新的多层次指导项目。虽然胺的价值和自由基反应的合成用途已经确立，但通过与亚硝基化合物合并自由基反应构建碳(C) -氮(N)和C-氧(O)键的策略探索几乎完全未知。通过这些研究，正在开发温和的、官能团耐受的、使用富铜的C-N成键反应的新机会。这些新的转化减少了获得含氮分子所需的合成步骤，否则很难制备。这种转变也给化学家们提供了新的合成键断开的途径。具体来说，本研究的目标是：1)扩大最近发展的铜催化亚硝基化合物自由基加成的范围，包括杂环、苄基溴和-溴腈；2)利用亚硝酸盐与市售的芳基和异芳基三氟硼酸盐进行反应，原位生成亚硝基试剂；3)将该策略应用于吡咯吲哚类生物碱天然产物的简明全合成；4)开发了一种新的基于分子内自由基的N-O转移过程，该过程可以在一系列结构中对氮和氧杂原子进行空间控制。里德·德·阿拉尼兹教授的团队在为科学领域代表性不足的学生提供最高水平的教育和培训方面处于有利地位。该项目还包括一项新的多层指导计划。

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.