Asymmetric Catalysis with Chiral Lewis Bases

Scott E. Denmark教授受化学系化学合成项目的支持，从事涉及元素周期表主族元素和过渡系列元素的已知化学反应的催化、对映选择性变体的发明研究，并对手性路易斯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、发展和探索在八羰基二钴催化下有机底物羰基化的范围。在这些反应中，路易斯碱通过裂解成活性离子对来电子激活钴簇。本研究的目标反应是环氧化物和叠氮嘧啶的羰基化开孔，分别形成内酯和内酰胺。由八羰基二钴催化的第二个重要合成过程是醛的氨基羰基化，形成α -氨基酸。这种显著的转化没有对映选择性变异，钴配合物的路易斯碱活化提供了一个独特的机会来研究这一过程的机制和立体化学过程。可以说，化学合成所有领域的进步都是由新化学反应的创造、优化和理解驱动的。制备具有挑战性化学结构的分子（天然产物或理论感兴趣的分子）或具有理想化学，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）需要设计可执行的合成路线的能力。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，这些活动对于研究生和博士后同事的智力和实践训练是理想的。反应设计、开发和应用的相互作用是科学方法的本质。学生们被提出了对计划实验结果的假设，他们必须学会收集和解释数据来证实或消除假设。这项活动的统一主题是在现有的机械范式的基础上发明新的化学反应。这为学生在项目指导下的创造力提供了一个平台，让他们找到新的方向。

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.