SusChem: IUPAC: Sustainable Transition-Metal Catalysts for Radical Reactions

在这个由化学系化学催化计划资助的项目中，哥伦比亚大学的杰克·诺顿教授研究了自由基作为构建复杂化学分子的多功能中间体。虽然自由基的成键反应是可预测的，而且它们对官能团的耐受性很高，但它们在可持续合成中的应用在很大程度上仍未得到开发。这项研究是以跨学科的方式进行的，将新的合成方法与量子化学、机械无机化学和生物化学的研究相结合。这项研究中研究的第一排过渡金属(钒、钛、钴和铬)非常适合于可持续催化。它们是无毒的(在将要使用的氧化态中)，并取代了使用稀有和昂贵金属的络合物。使用二氢(H2)作为终端还原剂解决了与还原自由基反应相关的长期存在的环境和毒性问题。新的催化剂正在被合成，量子化学方法正被用于虚拟催化剂的筛选和机理测定。催化氢催化环氧化物还原为醇、与氢还原自由基环化以及各种二烯、烯炔和环氧烯的自由基环异构化的可持续方法正在研究中。这些方法被应用于功能化的八元环和九元环内酰胺和环胺的高效、通用和立体选择性的合成，以及多环无精子和Kopsia吲哚生物碱的合成，如伏非尼定和葛根定A的合成。本项目是与德国波恩莱茵大学的Stefan Grimme教授和Andreas Gansaeuer教授以及中国科学院上海有机化学研究所的李朝忠教授合作完成的。这些小组共同结合了他们在制备和研究催化自由基反应性和机理方面的不同专业领域。除了化学工业对这项研究的技术应用外，这项工作的更广泛影响包括培养研究生和国际交流思想和专业知识。

In this project funded by the Chemical Catalysis Program of the Chemistry Division, Professor Jack Norton of Columbia University examines radicals as versatile intermediates for the construction of complex chemical molecules. While the bond-forming reactions of radicals are predictable, and their tolerance of functional groups is high, their use in sustainable synthesis remains largely untapped. This research is done in an interdisciplinary manner, combining new synthetic methods with research in quantum chemistry, mechanistic inorganic chemistry, and biological chemistry. The first-row transition metals (vanadium, titanium, cobalt and chromium) investigated in this research are ideally suited for sustainable catalysis. They are nontoxic (in the oxidation states to be used) and replace complexes using rare and expensive metals. The use of dihydrogen (H2) as the terminal reductant resolves longstanding environmental and toxicity issues associated with reductive radical reactions. New catalysts are being synthesized and quantum chemical methods are being used for virtual catalyst screening and mechanistic determinations. Sustainable methods for catalyzing the hydrogen-mediated reduction of epoxides to alcohols, reductive radical cyclizations with H2, and radical cycloisomerizations by various dienes, enynes and epoxyenes are under investigation. These methods are applied to the efficient, general, and stereoselective syntheses of functionalized eight- and nine-membered ring lactams and cyclic amines, and to the syntheses of polycyclic Aspidosperma and Kopsia indole alkaloids such as voafinidine and grandilodine A. This project is performed in collaboration with Professors Stefan Grimme and Andreas Gansaeuer of the Rheinische Friedrich-Wilhelms-Universitaet in Bonn, Germany and Professor Chaozhong Li of the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, in China. Together, these groups combine their separate areas of expertise in the preparation and study of catalytic radical reactivity and mechanisms. In additional to the technical applications of this research by the chemical industry, the broader impacts of this work include the training of graduate students and an international exchange of ideas and expertise.