Development of a Novel Imine-yne Metathesis Reaction

描述（由申请人提供）：我们发现具有生物和药用价值的新型化合物的能力的关键是我们设计和合成有机分子的能力。因此，开发高效、通用和可预测的合成方法对生物医学研究至关重要。本研究计划旨在发展一种概念新颖且合成能力强的金属催化亚胺-炔复分解反应。基于Bergman的工作与组（IV）亚胺配合物和考虑的电子和空间性质的亚胺，九茂金属配合物的启发，提出了调查作为催化剂，实现一般亚胺-炔复分解。实验设计，以探讨亚胺炔复分解的合成效用的概述。此外，区域和立体选择性的分子间和分子内的变化，这一反应进行了讨论和预测。如果成功的话，这些研究将丰富我们对金属-杂原子络合物的结构和反应性的理解。这种新的方法也将代表一个显着的进步，目前的技术可用于合成α，β-不饱和亚胺和烯酮-在有机合成的基本构件。此外，该反应的分子内变体应适用于杂环、碳环和大环的合成，这些杂环、碳环和大环是具有药用价值的化合物中普遍存在的结构架构。

DESCRIPTION (provided by applicant): Essential to our ability to discover novel compounds of biological and medicinal value is our ability to design and synthesize organic molecules. The development of efficient, versatile and predictable synthetic methods is therefore vital to biomedical research. This research plan aims to develop a conceptually novel and synthetically powerful metal-catalyzed imine-yne metathesis reaction. Based on inspiration from Bergman's work with group (IV) imido complexes and considerations of the electronic and steric properties of imines, nine metallocene complexes are proposed for investigation as catalysts for achieving a general imine-yne metathesis. Experiments designed to probe the synthetic utility of the imine-yne metathesis are outlined. In addition, the regio- and stereoselectivity for both the inter- and intramolecular variants of this reaction are discussed and predicted. If successful, these studies will enrich our understanding of the structure and reactivity of metal-heteroatom complexes. This new methodology will also represent a significant advancement over the current technologies available for the synthesis of alpha,beta-unsaturated imines and enones - fundamental building blocks in organic synthesis. Moreover, the intramolecular variant of this reaction should be applicable to the synthesis of heterocycles, carbocycles, and macrocycles, which are structural architectures prevalent in compounds of medicinal interest.