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: 9021103
• 负责人: Donald Allen Watson
• 金额: $ 10.6万
• 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/9021103
• 关键词: Alkylation; Amination; Amines; Area; Biology; Carbon; Catalysis; Chemicals; Complex; Copper; Dependence; Development Plans; Elements; Goals; Health; 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; success

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：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。随着对更具选择性、更强效和更有效的药物的需求增加，对开发用于复杂有机分子的有效化学合成的新方法的需求不断增长。 烷基胺是许多主要药剂中的常见结构元素。尽管存在许多用于其构建的方法，但这些方法中的许多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制备方法。因此，需要新的方法来从其他前体制备这样的分子。 该提案概述了两种使用非羰基起始原料制备复合烷基胺的新方法。所提出的方法的主题联系是利用过渡金属基催化剂开发新的方法，以胺合成硝基烷烃原料。在目标1中，提出了一种使用简单铜催化剂进行硝基烷烃碳中心烷基化的新方法。这些反应的产物很容易转化为烷基胺。以前实现这种转化的方法依赖于实验上苛刻的反应条件或使用复杂或高毒性的试剂。基于我们初步发现的以大量卤代烷为原料的硝基烷C-烷基化反应条件温和的基础上，提出了一种制备复杂硝基烷的一般方法。目标2概述了使用钌催化剂将硝基烷烃催化转化为对映体富集胺的方法的开发计划。这种新方法有望提供一种新的对映体富集胺的路线，该路线与现有方法高度互补，并且可以广泛地利用目标1的产物以及通过现有方法制备的硝基烷烃。 总的来说，预计所提出的方法将提供使用非传统起始材料获得复杂烷基胺的改进途径。这项工作将直接有利于制备复杂的含氮有机分子，并有助于发现下一代药物制剂。