Asymmetric Umpolung Aldehyde Reactions

不对称醛醛反应

• 批准号: 8919383
• 负责人: Tomislav Rovis
• 金额: $ 27.99万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-05 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8919383
• 关键词: Aldehydes; Biological; Catalysis; Complex; Development; Family; Goals; Health; Lactams; Methodology; Methods; Pathway interactions; Positioning Attribute; Principal Investigator; Reaction; Reagent; Research; Route; Science; Structure; Therapeutic Agents; Time; catalyst; cost; cyclopentanone; functional group; innovation; interest; novel; programs; small molecule; stereochemistry

DESCRIPTION (provided by applicant): The development of novel routes to stereochemically and structurally complex targets of biological interest remains of paramount importance. New strategies, bond disconnections, and catalysts that exploit standard functional groups in innovative ways each contribute to the overall goal of increased scope and efficiency, and decreased time and cost. Catalysis, the use of substoichiometric amounts of reagent, without the need for covalent attachment or pretreatment, carries with it the promise of greener, more efficient, more selective methods for synthesis. This proposal seeks to develop novel methods to use traditional functional groups in non-traditional ways, accessing hitherto unavailable bond disconnection strategies in an effort to greatly expand our toolkit. In the context of this researc, we will apply these strategies to the formation of lactams, common structural features across many families of biologically active molecules. The specific goals of this research are as follows: 1) Develop asymmetric intermolecular Stetter reactions involving less activated Michael acceptors; 2) Control stereochemistry at the beta position via the homoenolate reactivity pathway; 3) Investigate oxidative pathways of enal activation; 4) Control oxidatively initiated [3+2]-type annulation of enals leading to cyclopentanone products. The long-term impact of this science is to enable chemists to rapidly assemble complex structures with high efficiency.

描述（由申请人提供）：开发立体化学和结构复杂的生物学目标的新途径仍然至关重要。新的策略、键断和以创新方式利用标准官能团的催化剂都有助于实现增加范围和效率以及减少时间和成本的总体目标。催化，使用亚化学计量的试剂，而不需要共价连接或预处理，带来了更绿色，更有效，更选择性的合成方法的希望。该提案旨在开发新的方法，以非传统的方式使用传统的官能团，访问迄今为止不可用的键断开策略，努力大大扩展我们的工具包。在这项研究的背景下，我们将应用这些策略来形成内酰胺，这是许多生物活性分子家族的共同结构特征。本研究的具体目标如下： 1)开发涉及较少活化的Michael受体的不对称分子间Stetter反应; 2）通过高烯醇化物反应性途径控制β位的立体化学; 3）研究烯醛活化的氧化途径; 4）控制氧化引发的烯醛[3+2]型成环，导致环戊酮产物。这门科学的长期影响是使化学家能够快速高效地组装复杂的结构。