Applications of Yn- and Allenamide Cycloadditions

描述(申请人提供)：烯烃和炔烃是有机合成中最重要的组成部分。我们一直在定义一类新的氮取代的烯和炔的反应性，特别是烯丙酰胺和氰化胺，其中的氮原子包含一个吸电子基团。与经典的氮代联烯和炔烃相比，这些联胺和联胺具有非常必要的稳定性。然而，更重要的是，它们独特的构象刚性和诱人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，这项NIH提案的目标是探索这些立体选择方法的应用。 对于AIM-L中的氰胺类化合物的化学，我们提出了环化闭环歧化反应来构建复杂的氮杂环化合物。 对于烯丙酰胺的化学，我们在AIM-2中提出了一种全合成()-锌科普林，其特点是应用了杂[4 2]环加成。在AIM-3和AIM-4中，我们提出了全合成(-)-1-异硫氰酸酯-芳香烯丙烷、()-香豆碱和()-Iyconadin A，重点介绍了N-取代氧烯丙基阳离子分子内[4，3]环加成反应的应用。 这些合成应用可以证明联烯酰胺和双胺在构建复杂的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联氨酰胺和肉毒胺的化学的兴趣，这两种化合物在有机合成中显示出巨大的前景。

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.