Applications of Yn- and Allenamide Cycloadditions

Yn-和烯丙酰胺环加成的应用

• 批准号: 7385887
• 负责人: RICHARD P HSUNG
• 金额: $ 22.98万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7385887
• 关键词: Alkynes; Biological Factors; Cations; Chemistry; Class; Complex; Electrons; Goals; Investigation; Isothiocyanates; Methodology; Methods; Muscle Rigidity; Nitrogen; Organic Synthesis; United States National Institutes of Health; cycloaddition; interest; propadiene; zincophorin

DESCRIPTION (provided by applicant): Allenes and alkynes are among the most important building blocks in organic synthesis. We have been defining the reactivity of a new class of nitrogen-substituted allenes and alkynes, specifically allenamides and ynamides, in which the nitrogen atom contains an electron-withdrawing group. These allenamides and ynamides possess much needed stability compared to classical nitrogen-substituted allenes and alkynes. However, more significantly, their unique conformational rigidity and attractive coordination ability have allowed us to develop highly stereoselective synthetic methods. Therefore, it is the goal of this NIH proposal to explore applications of these stereoselective methodologies. For chemistry of ynamides in Aim-l, we propose en-ynamide ring-closing metathesis to construct complex nitrogen heterocycles. For chemistry of allenamides, we propose in Aim-2 a total synthesis of (+)-zincophorin, featuring the application of a hetero [4 + 2] cycloaddition. In Aim-3 and Aim-4, we propose total syntheses of (-)-1-isothiocyanate-aromadendrane, (+)-parvineostemonine, and (+)-Iyconadin A, featuring applications of N-substituted oxyallyl cation intramolecular [4 + 3] cycloadditions. These synthetic applications can demonstrate the potential of allenamides and ynamides in constructing complex natural products. Investigations proposed here should continue to revitalize interest in the chemistry of allenamines and ynamines which show great promise in organic synthesis.

描述（由申请人提供）： 丙烯和炔烃是有机合成中最重要的组成部分之一。我们一直在定义一类新的氮取代丙二烯和炔烃的反应性，特别是丙二烯酰胺和炔酰胺，其中氮原子含有吸电子基团。与经典的氮取代丙二烯和炔烃相比，这些丙二烯酰胺和炔酰胺具有急需的稳定性。然而，更重要的是，它们独特的构象刚性和有吸引力的配位能力使我们能够开发出高度立体选择性的合成方法。因此，NIH 提案的目标是探索这些立体选择性方法的应用。 对于Aim-1中的烯酰胺化学，我们提出烯酰胺闭环复分解来构建复杂的氮杂环。 对于联二烯酰胺的化学，我们在 Aim-2 中提出了 (+)-锌基蛋白的全合成，其特点是应用杂 [4 + 2] 环加成。在Aim-3和Aim-4中，我们提出了(-)-1-异硫氰酸酯-aromadendrane、(+)-parvineostemonine和(+)-Iyconadin A的全合成，其中应用了N-取代的氧烯丙基阳离子分子内[4 + 3]环加成。 这些合成应用可以证明丙二​​烯酰胺和炔酰胺在构建复杂天然产物方面的潜力。这里提出的研究应该继续重振人们对烯胺和烯胺化学的兴趣，它们在有机合成中显示出巨大的前景。