Carbene Catalysis Strategies for Organic Synthesis

有机合成的卡宾催化策略

• 批准号: 8727579
• 负责人: Karl A Scheidt
• 金额: $ 28.1万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8727579
• 关键词: Acids; Alkenes; Alkylation; Anions; Biological; Biological Factors; Biology; Biomedical Research; Catalysis; Chemicals; Chemistry; Collection; Development; Electrons; Explosion; Funding; Goals; Health; Human; Investigation; Knowledge; Lactones; Lead; Medicine; Methodology; Molecular; Organic Synthesis; Oxidation-Reduction; Palladium; Pattern; Positioning Attribute; Process; Reaction; Reagent; Research; Rhodium; Structure; Transition Elements; base; carbene; catalyst; chemical reaction; chemical synthesis; cycloaddition; direct application; functional group; innovation; metal complex; novel strategies; secologanin; small molecule

DESCRIPTION (provided by applicant): New chemical transformations enable the efficient construction of important molecules that are essential for biomedical research. The most powerful and efficient chemical reactions use catalysis to control reactivity and selectivity. The developments in catalytic methodology over the last quarter century have focused primarily on established reactivity patterns, such as carbonyl additions, cycloadditions, oxidations, and reductions. Many of these reactions follow principles predicted by electronegativity concepts. Umpolung reactions invert the normal reactivity of functional groups, thereby facilitating unconventional synthetic strategies. This transformation of an electron-poor species (electrophile) into an electron-rich reactant (nucleophile) is typically accomplished using stoichiometric reagents. Even though Umpolung reactions are important in organic synthesis, there are limited catalytic polarity reversal transformations with broad scope. Our central hypothesis is new approaches to catalysis using N-heterocyclic carbenes (NHCs) can significantly advance the field of chemical methodology and health relevant chemical synthesis. The specific goals of this proposal are: (1) Explore new carbene-catalyzed homoenolate equivalent reactions. The development of innovative formal cycloadditions, silylations, and alkylations will provide direct access to a large array of bioactive structures. (2) Develop new cooperative carbene catalysis processes. We have discovered that carbenes (Lewis bases) are compatible with Lewis acids to enhance selectivity and reactivity. The combination of Lewis acid or transition metal complexes with NHCs should provide new opportunities for chemical synthesis. (3) Investigate carbene catalysis-driven total syntheses. While there has been an explosion of NHC catalyzed reactions, few target syntheses have employed any of these new reactions as a key step. We will use an NHC-catalyzed desymmetrization as the key step in the synthesis of secologanin, a key secoiridoid natural product. Additionally, we will pursue a synthesis of arnamial using our NHC-catalyzed intramolecular Michael reaction. Our research in generating new reactivity using organocatalysis will establish new approaches for the efficient synthesis of molecules. This research will also provide important knowledge about nucleophile-catalyzed polarity reversal reactions. These findings will ultimately lead to the development of a powerful collection of stereoselective and related strategies that are useful for synthesis.

描述（由申请人提供）：新的化学转化能够有效地构建对生物医学研究至关重要的重要分子。最强大、最有效的化学反应是利用催化来控制反应活性和选择性的。在过去的四分之一世纪里，催化方法的发展主要集中在已建立的反应模式上，如羰基加成、环加成、氧化和还原。许多这些反应遵循电负性概念所预测的原理。unpolung反应逆转了官能团的正常反应性，从而促进了非常规的合成策略。贫电子物质（亲电试剂）向富电子反应物（亲核试剂）的转变通常是通过化学计量试剂完成的。尽管Umpolung反应在有机合成中占有重要的地位，但催化极性反转转化的范围有限。我们的中心假设是使用n -杂环碳烯（NHCs）催化的新方法可以显着推进化学方法学和健康相关化学合成领域。本提案的具体目标是：(1)探索新的碳催化的同烯酸酯等效反应。创新形式环加成、硅烷基化和烷基化的发展将提供大量生物活性结构的直接途径。(2)开发新的协同碳催化工艺。我们发现羰基（路易斯碱）与路易斯酸相容，以提高选择性和反应活性。路易斯酸或过渡金属配合物与NHCs的结合将为化学合成提供新的机会。(3)研究碳催化驱动的全合成。虽然NHC催化反应已经有了爆炸式的发展，但很少有目标合成使用这些新反应中的任何一个作为关键步骤。我们将使用nhc催化的去对称反应作为合成secologanin的关键步骤，secologanin是一种关键的secologanids天然产物。此外，我们将利用nhc催化的分子内Michael反应进行动物合成。我们在利用有机催化产生新的反应性方面的研究将为分子的高效合成开辟新的途径。这项研究也将为亲核试剂催化的极性反转反应提供重要的知识。这些发现将最终导致对合成有用的立体选择性和相关策略的强大集合的发展。