Applications of Yn- and Allenamide Cycloadditions

描述（由申请人提供）：联烯和炔是有机合成中最重要的结构单元之一。我们已经定义了一类新的氮取代的联烯和炔的反应性，特别是联烯酰胺和联烯酰胺，其中氮原子含有吸电子基团。与经典的氮取代的联烯和炔相比，这些联烯酰胺和联烯酰胺具有非常需要的稳定性。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高度立体选择性的合成方法。因此，这是美国国立卫生研究院建议的目标，探索这些立体选择性方法的应用。 对于Aim-1中的酰亚胺化学，我们提出了烯酰亚胺闭环复分解来构建复杂的氮杂环。 对于丙二烯酰胺的化学，我们在Aim-2中提出了（+）-锌磷蛋白的全合成，其特征在于杂[4 + 2]环加成的应用。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，其特征在于N-取代的氧烯丙基阳离子分子内[4 + 3]环加成的应用。 这些合成应用可以证明丙二烯酰胺和丙二烯酰胺在构建复杂天然产物中的潜力。这里提出的调查应继续振兴的兴趣，在化学中的丙二烯胺和丙二烯胺，这在有机合成中显示出很大的希望。

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.