Transition Metal Catalyzed Methods for Preparing Nitroalkanes and Alkyl Amines

过渡金属催化制备硝基烷烃和烷基胺的方法

• 批准号: 8630455
• 负责人: Donald Allen Watson
• 金额: $ 28.72万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8630455
• 关键词: Alkylation; Amination; Amines; Area; Biology; Carbon; Catalysis; Chemicals; Complex; Copper; Dependence; Development Plans; Elements; Goals; Hydrogenation; Imines; Improve Access; Indium; Investigation; Knowledge; Laboratories; Ligands; Light; Medicine; Methodology; Methods; Modern Medicine; Nature; Nitro Compounds; Nitrogen; Organic Synthesis; Pharmacologic Substance; Preparation; Process; Protocols documentation; Reaction; Reagent; Research; Route; Ruthenium; Seminal; Solutions; Structure; Techniques; Transition Elements; Variant; base; carbonyl compound; catalyst; chemical synthesis; human disease; improved; next generation; nitroalkane; novel; novel strategies; programs; public health relevance; success

Modern medicine is reliant on the preparation of complex organic molecules. These compounds comprise the active ingredients of most pharmaceutical agents. As the need for more selective, more potent, and more effective medicines increases, there is an ever-growing need to develop new methods for efficient chemical synthesis of complex organic molecules. Alkyl amines are a common structural element in many major pharmaceutical agents. Although numerous methods exist for their construction, many of these methods rely on common chemical intermediates (carbonyl compounds) as starting materials. This common chemical feedstock limits the ways in which alkyl amines can be prepared. Thus, there is need for new methods to prepare such molecules from other precursors. This proposal outlines two new methods to prepare complex alkyl amines using non-carbonyl starting materials. The thematic linkage of the proposed methods is the utilization of transition metal-based catalysts to develop new approaches to amine synthesis using nitroalkane starting materials. In Aim 1, a new approach to the carbon-centered alkylation of nitroalkanes using simple copper catalysts is proposed. The products from these reactions are readily converted into alkyl amines. Previous methods to achieve this transformation relied on experimentally demanding reaction conditions or on the use of either complex or highly toxic reagents. Based on our preliminary discovery of mild reaction conditions for the C-alkylation of nitroalkanes using abundant alkyl halides, a general method to prepare complex nitroalkanes is proposed. Aim 2 outlines plans for the development of a method for the catalytic conversion of nitroalkanes into enantioenriched amines using ruthenium catalysis. This new method promises to provide a new route into enantioenriched amines that is highly complementary to existing methods and can be broadly leveraged against the products from Aim 1, as well as nitroalkanes prepared by existing methods. In total, the proposed methodology is expected to provide improved access to complex alkyl amines using non-traditional starting materials. This effort will directly benefit the preparation of complex nitrogen-bearing organic molecules and aid in the discovery of the next generation of pharmaceutical agents.

现代医学依赖于复杂有机分子的制备。这些化合物包括 大多数药剂的活性成分。由于需要更有选择性、更有效、更 有效药物的增加，越来越需要开发高效化学药物的新方法 复杂有机分子的合成。 烷基胺是许多主要药剂中的常见结构元素。虽然数量众多 存在其构建方法，其中许多方法依赖于常见的化学中间体（羰基 化合物）作为起始材料。这种常见的化学原料限制了烷基胺的应用方式 做好准备。因此，需要新的方法来从其他前体制备此类分子。 该提案概述了两种使用非羰基起始原料制备复杂烷基胺的新方法 材料。所提出方法的主题联系是利用过渡金属基催化剂 开发使用硝基烷原料合成胺的新方法。在目标 1 中，采用一种新方法 提出了使用简单的铜催化剂进行硝基烷烃的碳中心烷基化。产品来自 这些反应很容易转化为烷基胺。以前实现这种转变的方法依赖于 实验要求较高的反应条件或使用复杂或剧毒的试剂。 基于我们初步发现硝基烷烃 C-烷基化的温和反应条件 由于丰富的烷基卤化物，提出了一种制备复杂硝基烷烃的通用方法。目标 2 概述了计划 开发一种将硝基烷烃催化转化为对映体富集胺的方法 钌催化。这种新方法有望提供一种制备对映体富集胺的新途径 与现有方法高度互补，并且可以广泛用于目标 1 的产品，如 以及通过现有方法制备的硝基烷烃。 总的来说，所提出的方法预计将使用以下方法改进获取复杂烷基胺的途径： 非传统原材料。这项工作将直接有利于复杂含氮化合物的制备 有机分子并有助于发现下一代药剂。