Asymmetric Catalysis with Chiral Lewis Bases

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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.