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(申请人提供)：现代医学依赖于复杂有机分子的制备。这些化合物包含大多数药剂的活性成分。随着对更有选择性、更有效和更有效的药物的需求的增加，人们越来越需要开发有效的复杂有机分子的化学合成的新方法。烷基胺是许多主要药剂中常见的结构元素。虽然有许多方法可以构建它们，但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制备方法。因此，需要新的方法来从其他前体制备这种分子。该提案概述了两种利用非羰基起始原料制备复合烷基胺的新方法。拟议方法的主题联系是利用过渡金属催化剂开发利用硝基烷烃原料合成胺的新方法。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反应的新方法。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要求苛刻的反应条件，或者使用复杂或剧毒的试剂。在我们初步发现硝基烷烃利用丰富的卤代烷进行C-烷基化反应条件温和的基础上，提出了一种合成复杂硝基烷烃的一般方法。目的2概述了开发一种利用Ru催化将硝基烷烃催化转化为对映体富集胺的方法的计划。这一新方法有望提供一条合成对映体富集胺的新路线，这是对现有方法的高度补充，可广泛用于目标1的产品以及由现有方法制备的硝基烷烃。总而言之，预计拟议的方法将改进使用非传统起始材料获得复杂烷基胺的途径。这一努力将直接有利于复杂含氮有机分子的制备，并有助于发现下一代药物制剂。