Group (IV) Imido Complex-Mediated Syntheses of Nitrogen-Containing Heterocycles

(IV)组亚氨基配合物介导的含氮杂环的合成

• 批准号: 7371030
• 负责人: Jennifer Marie Schomaker
• 金额: $ 4.68万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-20 至 2010-03-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7371030
• 关键词: Alkenes; Amines; Amino Alcohols; Aziridines; Biological; Biological Factors; Breathing; Carbon; Chemistry; Classification; Cleaved cell; Complex; Cyclopropanes; Development; Electronics; Goals; Label; Ligand Binding; Mediating; Metals; Methodology; Methods; Natural regeneration; Nitrogen; Numbers; Object Attachment; Outcome; Pentanes; Pharmacologic Substance; Phase; Preparation; Property; Pyrrolidines; Reaction; Reagent; Research; Screening procedure; Transition Elements; Work; aziridine; base; cyclopropane; interest; method development; pentane; protonation; pyrrolidine; research study

DESCRIPTION (provided by applicant): Several of the twenty most important Pharmaceuticals that are currently in use and many natural products with interesting biological activities contain C-N bonds. The development of methods to construct these bonds in a stereocontrolled manner will allow chemists to continue to efficiently prepare molecules of medicinal interest. Group (IV) transition metal imido complexes have been demonstrated to react with unsaturated substrates to form new C-N bonds. The proposed study builds on this chemistry to access aziridines, vicinal amino alcohols, enamides, ynamides and pyrrolidines that are important compounds in their own right, but also serve as intermediates for many useful synthetic transformations. The goal is to eventually develop enantioselective, catalytic syntheses of these molecules. The proposed research will examine the addition of group (IV) imido complexes to alkenes and strained cyclopropanes to form azametallacyclobutanes and pentanes. The steric and electronic properties of the substrates and the metal imido complexes necessary for facile reaction will be determined. The resulting azametallacycles will be treated with a variety of reagents to generate new nitrogen-containing compounds. The appropriate labeling experiments will be performed to determine the stereochemical outcome of these reactions. Group (IV) metal imido complexes bearing chiral metal-bound ligands or chiral auxiliaries on the imido nitrogen will be studied to develop enantioselective C-N bond-forming reactions. Particularly useful would be the development of a method to install C-N bonds via meso desymmetrization of alkenes. Protonation of the metal-carbon bond of an azametallacyclobutene has been shown to release the amine product and regenerate the active imido complex. This same approach will be utilized with azametallacyclobutanes in attempts to render the reactions catalytic in the group (IV) imido complex. Ultimately, the development of the proposed methodology is expected to allow rapid and stereocontrolled access to a number of useful nitrogen-containing compounds.

描述（由申请人提供）：目前使用的二十种最重要的药物中的几种和许多具有有趣生物活性的天然产物含有C-N键。以立体控制方式构建这些键的方法的发展将使化学家能够继续有效地制备具有药用价值的分子。第（IV）族过渡金属亚胺配合物已被证明与不饱和底物反应形成新的C-N键。拟议的研究建立在这种化学的基础上，以获得氮丙啶，邻氨基醇，酰胺，酰胺和吡咯烷，这些化合物本身就是重要的化合物，但也可以作为许多有用的合成转化的中间体。目标是最终开发出这些分子的对映选择性催化合成方法。拟议的研究将检查（IV）族亚氨基配合物加成到烯烃和应变环丙烷，形成氮杂金属环丁烷和戊烷。将确定易于反应所需的底物和金属亚氨基配合物的空间和电子性质。产生的氮杂金属环将用各种试剂处理以产生新的含氮化合物。将进行适当的标记实验以确定这些反应的立体化学结果。研究了在亚胺氮上带有手性金属配体或手性助剂的第（IV）族金属亚胺配合物，以发展对映选择性的C-N键形成反应。特别有用的是开发通过烯烃的内消旋去对称化来安装C-N键的方法。氮杂金属环丁烯的金属-碳键的质子化已显示释放胺产物并再生活性亚氨基络合物。这种相同的方法将用于氮杂金属环丁烷，试图使反应在第（IV）族亚氨基络合物中具有催化性。最终，所提出的方法的发展，预计将允许快速和立体控制的访问到一些有用的含氮化合物。