Stereoselective Heterocycle Synthesis via Zn(II) Promoted Metalloamination/Cyclization

通过 Zn(II) 促进金属胺化/环化立体选择性杂环合成

• 批准号: 9177590
• 负责人: THOMAS Stuart LIVINGHOUSE
• 金额: $ 16.29万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9177590
• 关键词: 1,2-Dimethylhydrazine; Acceleration; Address; Alkaloids; Amides; Appearance; Applications Grants; Area; Carbon; Chemistry; Complex; Cyclization; Deamination; Development; Disadvantaged; Event; Goals; Grant; Humanities; Hydrogen; Investigation; Ligands; Mediating; Metals; Methodology; Methods; Modification; Nitrogen; Pharmaceutical Chemistry; Piperazines; Preparation; Principal Investigator; Procedures; Process; Protocols documentation; Reaction; Reagent; Request for Applications; Research; Research Activity; Rest; Skeleton; Tropanes; Zinc; base; chemical synthesis; comparative; cost; cost effective; diene; insight; novel; novel strategies; practical application; preference; programs; propadiene; prospective; small molecule

PROJECT SUMMARY The elucidation of new, highly stereocontrolled reactions for the construction of carbon–nitrogen and carbon-carbon bonds remains a central goal of chemical synthesis. Over the years, various discoveries in this area have enabled the efficient preparation of a wide variety of important medicinals that have benefited humanity. This grant application requests support for the Principal Investigator's new projects in the area of organozinc(II)-promoted heterocycle synthesis. The present application emphasizes the discovery and synthetic application of a new and potentially powerful intramolecular C- N/C-Zn bond forming cascade involving the addition of functionalized zinc amides, derived from N,N- dimethylhydrazines, to allenes, dienes, enynes, vinylcyclopropanes and vinylcyclobutanes. We believe this method will receive considerable utilization as a vehicle for the stereocontrolled synthesis of biologically relevant small molecules. The application of the new chemistry discovered during the proposed grant period should be readily applicable to the synthesis of numerous stereochemically rich heterocycles of pharmacological significance. The research program described in this grant application is expected to provide valuable insight into new reaction types that should serve to elucidate specific factors that are critical to the development of consecutive intramolecular C-N/C-Zn (and thus: C-N/C-Electrophile) bond formation in the context of stereocontrolled small molecule synthesis.

项目概要 阐明构建碳氮的新型高度立体控制反应 碳-碳键仍然是化学合成的中心目标。多年来，各种 该领域的发现使得能够有效制备多种重要药物 使人类受益。此拨款申请请求支持首席研究员的 有机锌（II）促进的杂环合成领域的新项目。本申请 强调了一种新的、具有潜在强大分子内C-的发现和合成应用 N/C-Zn 键形成级联，涉及添加衍生自 N,N- 的官能化锌酰胺 二甲基肼、丙二烯、二烯、烯炔、乙烯基环丙烷和乙烯基环丁烷。我们相信 该方法将作为立体控制合成的载体得到广泛利用 生物学相关的小分子。 在拟议的资助期内发现的新化学的应用应该是 易于用于合成许多具有药理学活性的立体化学丰富的杂环 意义。本拨款申请中描述的研究计划预计将提供有价值的 深入了解新的反应类型，这些反应类型应有助于阐明对反应至关重要的特定因素 连续分子内 C-N/C-Zn（因此：C-N/C-Electrophile）键形成的发展 立体控制小分子合成的背景。