Asymmetric Catalysis with Chiral Lewis Bases

斯科特·E·丹麦教授在化学系化学合成计划的支持下，开展研究，旨在发明涉及元素周期表主族和过渡系列元素的著名化学反应的催化、对映体选择性变体，并对手性Lewis碱催化的反应进行结构和机理研究。本研究的主要目的是发明、开发和探索有机底物在八甲基钴催化下的羰基化反应范围。在这些反应中，Lewis碱通过裂解成反应离子对以电子方式激活钴原子簇。本研究的目标反应是环氧化物和氮杂环丙烷分别生成内酯和内酰胺的羰基开环反应。由八甲基钴催化的第二个重要的合成过程是醛的酰胺化反应，生成α-氨基酸。这一显着的转变没有对映体选择性变体，而钴络合物的Lewis碱活化为研究这一过程的机理和立体化学过程提供了一个独特的机会。可以说，化学合成的所有领域的进步都是由新化学反应的创造、优化和理解推动的。制备具有挑战性化学结构的分子(天然产物或具有理论意义的分子)或具有理想的化学、物理或生物特性的分子(在材料科学或农业、制药或商业领域的应用)需要有能力设计可执行的合成路线。从20世纪下半叶有机合成的演变中得到的最重要的教训是，合成路线的战略和规划是由战术驱动的。换句话说，化学合成的范围、选择性和效率与新化学反应的发现、发展和优化密不可分。此外，这些活动非常适合研究生和博士后同事的智力和实践培训。反应设计、开发和应用的相互作用代表了科学方法的精髓。向学生提出对计划实验结果的假设，他们必须学会收集和解释数据以证实或消除假设。这项活动的统一主题是在现有机制范式的基础上发明新的化学反应。这为学生在项目指导下确定新的方向提供了一个创造性的平台。

Professor Scott E. Denmark is supported by the Chemical Synthesis Program in the Division of Chemistry to conduct research directed toward the invention of catalytic, enantioselective variants of well known chemical reactions involving elements in the Main Group and transition series of the Periodic Table and to carry out structural and mechanistic investigation of the reactions catalyzed by chiral Lewis bases. The primary objectives of this research involve the invention, development, and exploration of the scope of carbonylation of organic substrates under catalysis by dicobalt octacarbonyl. In these reactions, the Lewis base electronically activates the cobalt cluster by the cleavage into reactive ion pairs. The reactions targeted for this study are the carbonylative opening of epoxides and aziridines to form lactones and lactams, respectively. A second and synthetically important process that is catalyzed by dicobalt octacarbonyl is the amidocarbonylation of aldehydes to form alpha-amido acids. This remarkable transformation has no enantioselective variant and the Lewis base activation of the cobalt complex offers a unique opportunity to investigate both the mechanism and the stereochemical course of the process. It can be argued that progress in all areas of chemical synthesis is driven by the creation, optimization and understanding of new chemical reactions. The preparation of molecules with challenging chemical structures (natural products, or molecules of theoretical interest) or molecules with desirable chemical, physical or biological properties (with applications in materials science or the agricultural, pharmaceutical or commercial sectors) requires the ability to design executable synthetic routes. The most important lesson gleaned from the evolution of organic synthesis during the second half of the 20th century is that strategy and planning of synthetic routes are driven by tactics. In other words, the scope, selectivity and efficiency of chemical synthesis are inexorably tied to the discovery, development and optimization of new chemical reactions. In addition, these activities are ideal for the intellectual and practical training of graduate students and postdoctoral coworkers. The interplay of reaction design, development and application represent the essence of the scientific method. Students are presented with hypotheses for the outcome of planned experiments and they must learn to collect and interpret data to substantiate or eliminate the hypothesis. The unifying theme of this activity is the invention of new chemical reactions on the basis of current mechanistic paradigms. This provides a platform for creativity within the guidelines of the project for students to identify new directions.