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）：新的化学转化可以有效地构建重要分子，这对于生物医学研究至关重要。最强大，最有效的化学反应利用催化来控制反应性和选择性。上四分之一世纪的催化方法论的发展主要集中在既定的反应性模式，例如羰基添加，环加成，氧化和还原。这些反应中的许多反应遵循由电负性概念预测的原理。 Umpolung反应扭转了官能团的正常反应性，从而促进了非常规合成策略。通常，使用化学计量试剂将电子贫基物种（电力）转化为富含电子反应物（亲核试剂）。即使Umpolung反应在有机合成中很重要，但具有较大范围的催化极性逆转转化有限。我们的中心假设是使用N-杂环碳烯（NHC）进行催化的新方法，可以显着推进化学方法论和与健康相关的化学合成领域。该提案的具体目标是：（1）探索新的卡宾培养基同烯酸酯等效反应。创新的正式环加成，硅烷二元和烷基化的开发将直接访问大量的生物活性结构。 （2）开发新的合作卡宾催化过程。我们已经发现Carbenes（Lewis碱基）与Lewis酸兼容，以提高选择性和反应性。路易斯酸或过渡金属复合物与NHC的结合应为化学合成提供新的机会。 （3）研究卡宾催化驱动的总合成。尽管NHC催化反应发生了爆炸，但很少有目标合成以这些新反应作为关键步骤。我们将使用NHC催化的去对称性作为塞氏菌蛋白的合成的关键步骤，Secoganin是一种关键的Secoiridoid自然产物。此外，我们将使用我们的NHC催化分子内迈克尔反应来追求界界的合成。我们在使用有机催化产生新的反应性的研究将建立有效合成分子的新方法。这项研究还将提供有关亲核催化的极性逆转反应的重要知识。这些发现最终将导致开发有力的立体选择性和相关策略，这些策略可用于合成。