Development of a Novel Imine-yne Metathesis Reaction

描述（由申请人提供）：我们设计和合成有机分子的能力是我们发现具有生物和药用价值的新化合物的能力的关键。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、合成能力强的金属催化亚胺-炔复分解反应。基于Bergman对（IV）亚胺配合物的研究，并考虑到亚胺的电子和空间性质，提出了九种茂金属配合物作为实现一般亚胺-炔复分解的催化剂进行研究。本文概述了旨在探讨亚胺-炔复合反应的合成效用的实验。此外，讨论并预测了该反应分子间和分子内变体的区域选择性和立体选择性。如果成功，这些研究将丰富我们对金属杂原子配合物的结构和反应性的认识。这种新方法也代表了目前合成α， β -不饱和亚胺和烯酮的技术的重大进步，这些技术是有机合成的基本组成部分。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，这些结构结构普遍存在于具有药用价值的化合物中。

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.