Asymmetric Umpolung Aldehyde Reactions

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是至关重要的。以创新的方式利用标准官能团的新策略、键断开和催化剂都有助于实现扩大范围和效率、减少时间和成本的总体目标。催化，使用亚化学计量比的试剂，不需要共价连接或前处理，带来了更绿色、更有效、更有选择性的合成方法的前景。这项提议寻求开发新的方法，以非传统的方式使用传统官能团，获得迄今无法获得的键断开策略，以努力极大地扩展我们的工具包。在这项研究的背景下，我们将把这些策略应用于内酰胺的形成，内酰胺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)开发不对称分子间Stetter反应，涉及活性较低的Michael受体；2)通过高烯醇酸反应途径控制β位置的立体化学；3)研究Enal激活的氧化途径；4)控制氧化引发的[3+2]型环化导致环戊酮产物。这门科学的长期影响是使化学家能够高效地快速组装复杂的结构。

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.