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: 8996577
• 负责人: Donald Allen Watson
• 金额: $ 29.64万
• 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/8996577
• 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; 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物的活性成分。随着需要更有选择，更有效和更有效的药物的需求增加，因此不断增长的需要开发新方法来有效地化学合成复杂的有机分子。 烷基胺在许多主要药物中是常见的结构元素。尽管存在许多用于建筑的方法，但其中许多方法依赖于普通化学中间体（羰基化合物）作为起始材料。这种常见的化学原料限制了制备烷基胺的方式。因此，需要新方法来制备其他前体的分子。 该提案概述了使用非谐波起始材料制备复杂烷基胺的两种新方法。所提出的方法的主题连锁是利用基于过渡金属的催化剂来开发使用硝基烷烷的新方法来开发胺合成的方法。在AIM 1中，提出了一种使用简单的铜催化剂的新方法，以硝基烷烃为中心的烷基化。这些反应中的产物很容易转化为烷基胺。实现这种转变的先前方法取决于实验要求的反应条件或使用复合物或剧毒试剂。基于我们对使用丰富的烷基卤化物的硝基烷基C-烷基化的轻度反应条件的初步发现，提出了一种制备复杂硝基烷烃的一般方法。 AIM 2概述了开发一种方法，该计划是使用钌催化剂将硝基烷烃催化转化为对映体胺的方法。这种新方法有望提供一条新的途径到富含对象的胺，该胺非常互补，可以广泛利用AIM 1的产品以及通过现有方法制备的硝基烷烃。 总的来说，提出的方法有望使用非传统的起始材料来改善对复杂烷基胺的访问。这项工作将直接有益于复杂的含氮有机分子的制备，并有助于发现下一代药物。