Catalytic Amination Reactions Utilizing Bimetallic Cooperativity

描述(申请人提供)：生物、生物化学、药理学、天然产物合成和环境化学等领域与人类健康相关的科学研究需要不断增长和日益复杂的分子工具库才能继续进行。合成有机化学必须进化以满足这种对有用分子的需求，而它为科学界做出贡献的能力是建立在高效和适用的合成方法的持续发展的基础上的。合成方法学发展中最大的挑战之一是发现将氮等杂原子引入有机分子的简单而通用的方法。在这一广泛的背景下，这项建议集中在以简单有效的方式将C-N键安装到有机分子中的新方法上。虽然许多研究人员已经并正在这一领域工作，但这一建议使用了新颖和创造性的策略来解决这个问题，使本文提出的方法具有独特性，原因有几个。首先，目前许多最先进的碳-氮键形成方法需要苛刻的氧化条件，并产生大量的化学废物。该提案的部分内容提出了将底物转化为产品的方法，这些方法只需要一个催化剂，不需要额外的试剂，唯一的副产品是气态二氢(H2)的释放。这种策略避免了对反应条件的苛刻要求，优化了原子经济性，并将化学废物保持在最低限度。其次，该方案中的合成方法通过利用非常规反应机理，有望展示出有别于现有方法的化学选择性模式。这种新出现的二分法将使所提出的方法补充更多的合成文献，从而有助于合成有机化学家合成复杂分子的工具集。这些集体因素使拟议的研究适用于致力于人类健康的科学研究领域，并具有重要意义。 与公众健康相关：有机化学中新的合成方法的发展至关重要：1)使人类健康多个领域的科学家能够获得他们研究所需的分子；2)简化制造药物化合物的效率(从而降低成本)；3)找到方法，允许合成这些复杂的分子，同时将污染环境的化学废物降至最低。这项提案中的研究涉及所有这些主题，因此以切实和适用的方式与人类健康密切相关。

DESCRIPTION (provided by applicant): Scientific research relevant to human health in areas such as biology, biochemistry, pharmacology, natural product synthesis, and environmental chemistry requires a growing and increasingly complex library of molecular tools in order to proceed. Synthetic organic chemistry must evolve to meet this need for useful molecules, and its ability to contribute to the scientific community is founded on the continued development of efficient and applicable synthetic methods. One of the great remaining challenges in synthetic methodology development is to uncover simple and general methods to introduce heteroatoms such as nitrogen into organic molecules. Within this broad context, this proposal focuses on new methods for installing C-N bonds into organic molecules in simple and efficient ways. Though many researchers have worked and are working in this area, this proposal utilizes novel and creative strategies to address the problem, making the methods proposed herein unique for several reasons. First, many of the current state-of-the-art methods for C-N bond formation require harsh oxidizing conditions and generate copious chemical waste. Portions of this proposal put forth methods that require only a catalyst and no additional reagents to convert substrates to products, with liberation of gaseous dihydrogen (H2) as the only byproduct. This strategy obviates the need for harsh reaction conditions, optimizes atom economy, and keeps chemical waste to a minimum. Secondly, the synthetic methods in this proposal hold the promise to exhibit modes of chemical selectivity distinct from existing methods by virtue of utilizing unconventional reaction mechanisms. This emerging dichotomy will cause the proposed methods to complement the larger body of synthetic literature and therefore contribute to the set of tools available to synthetic organic chemists for the synthesis of complicated molecules. These collective factors make the proposed research applicable and important to areas of scientific research devoted to human health. PUBLIC HEALTH RELEVANCE: The development of new synthetic methods in organic chemistry is crucial 1) to allow scientists in several fields of human health to access the molecules necessary for their research, 2) to streamline the efficiency (and, therefore, cost) of making pharmaceutical compounds, and 3) to find methods that allow the synthesis of these complicated molecules while minimizing the chemical waste that pollutes the environment. The research in this proposal addresses all of these topics, and therefore is tremendously relevant to human health in tangible and applicable ways.