Carbene Catalysis Strategies for Organic Synthesis

有机合成的卡宾催化策略

• 批准号: 8412083
• 负责人: Karl A Scheidt
• 金额: $ 5.41万
• 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/8412083
• 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）：新的化学转化能够高效构建对生物医学研究至关重要的重要分子。最强大和有效的化学反应使用催化剂来控制反应性和选择性。在过去的四分之一世纪中，催化方法学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。Umpolung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（亲电体）到富电子反应物（亲核体）的这种转化通常使用化学计量试剂来完成。尽管Umpolung反应在有机合成中很重要，但存在有限的催化极性反转转化，范围很广。我们的中心假设是使用N-杂环卡宾（NHC）的新催化方法可以显着推进化学方法学和健康相关的化学合成领域。本课题的具体目标是：（1）探索卡宾催化的高烯醇化物等价反应。创新的正式环加成，硅烷化和烷基化的发展将提供直接获得大量的生物活性结构。(2)开发新的协同卡宾催化工艺。我们已经发现卡宾（刘易斯碱）与刘易斯酸相容以增强选择性和反应性。刘易斯酸或过渡金属配合物与NHC的组合应该为化学合成提供新的机会。(3)研究卡宾催化驱动的全合成。虽然NHC催化的反应已经爆炸，但很少有目标合成将这些新反应中的任何一个作为关键步骤。我们将使用NHC催化的去对称化作为合成secologanin的关键步骤，secologanin是一种关键的secoiridoid天然产物。此外，我们将继续使用我们的NHC催化的分子内迈克尔反应合成arnamial。我们的研究在使用有机催化产生新的反应性将建立新的方法，为有效的合成分子。这一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发展的一个强大的收集立体选择性和相关的战略，是有用的合成。