Transition Metal Catalyzed Methods for Preparing Nitroalkanes and Alkyl Amines

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。因为需要更有选择性、更强大和更多的 随着有效药物的增加，人们越来越需要开发新的有效化学方法。 复杂有机分子的合成。 烷基胺是许多主要药剂中常见的结构元素。虽然数量众多 存在构建它们的方法，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 做好准备。因此，需要新的方法来从其他前体制备这种分子。 本提案概述了两种利用非羰基起始制备复合烷基胺的新方法。 材料。拟议方法的主题联系是利用过渡金属基催化剂 开发利用硝基烷烃原料合成胺的新方法。在目标1中，一种新的方法 提出了以简单铜为催化剂的硝基烷烃碳中心烷基化反应。这些产品来自 这些反应很容易转化为烷基胺。以前实现这一转变的方法依赖于 对实验要求苛刻的反应条件或复杂或剧毒试剂的使用。 基于我们初步发现的适用于硝基烷烃C-烷基化反应的温和条件。 针对烷基卤化物丰富的特点，提出了一种合成复杂硝基烷烃的通用方法。目标2概述计划 为开发一种将硝基烷烃催化转化为对映体富集胺的方法 Ru催化作用。这种新方法有望提供一条合成对映体富集胺的新途径，即 对现有方法具有很强的互补性，可广泛用于Aim 1中的产品，如 以及用现有方法制备的硝基烷烃。 总而言之，拟议的方法预计将改善获得复杂烷基胺的途径 非传统起始材料。这一努力将直接有利于复杂含氮化合物的制备。 有机分子和帮助发现下一代药剂。

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.