Amidins and Imidates as Transient Directing Groups in C-H-activating Reactions

脒和亚胺酯作为 C-H 激活反应中的瞬时导向基团

• 批准号: 406058799
• 负责人: Professor Dr. Boris J. Nachtsheim
• 金额: --
• 依托单位: Arbeitsgruppe Organische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/406058799?language=en
• 关键词: Amidins; Imidates; Transient; Directing; Groups

In this research project we want to develop a direct ortho-alkynylation of phenols and anilins under C-H-activating conditions. For this purpose, we want to establish amidines and imidates as novel transient directing groups (tdGs) for alkynylation reactions. By definition, tdGs are installed during the C-H-activating transformation for a better guidance of the transition metal to the desired C-H-bond and finally they are cleaved after a successful functionalization. To guarantee the reversibility of the tdG formation in this specific case, we want to introduce ortho-X-H-acidic aromatic nitriles as their precursors. In a first goal we want to synthesize a variety of such electron poor ortho-X-H-acidic nitriles und transform them into amidines and imidates by direct reaction with well-chosen anilines and phenols. We want to study this important reaction mechanistically, in particular its reversibility. Since amidines as well as imidates have not been described so far in C-H-activating alkynylations, a directed alkynylation under their guidance as “classical” directing group should be established. As electrophilic alkyne source alkynyl(aryl)benziodoxolones will be used. These reagents have been used in a variety of guided C-H-activating reactions since they show a remarkable high reactivity and at the same time they are bench stable and easy to handle. Besides the direct ortho-alkynylation, we want to develop domino-type processes to get an efficient access to a variety of highly substituted heterocycles. From the information that we gained from the initial mechanistic studies regarding the reversibility of the amidine and imidate formation and from the alkynylation reactions, we finally should be able to develop a process that only uses catalytic amounts of the ortho-C-H-acidic nitrile. Here the amidines and imidates are generated in situ as tdGs. In addition, we want to study the regio- and chemoselectivity of this transformation and we want to be able to rationally steer this selectivity.

在这个研究项目中，我们想在c - h活化条件下开发苯酚和苯胺的直接邻炔化反应。为此，我们想要建立脒和拟合物作为烷基化反应的新型瞬态导向基团（tdg）。根据定义，tdg是在碳氢活化转化过程中安装的，以便更好地将过渡金属引导到所需的碳氢键上，最后在成功的功能化后被切割。为了保证在这种特殊情况下tdG形成的可逆性，我们想引入邻x - h酸性芳腈作为它们的前体。在第一个目标中，我们想要合成各种这样的缺乏电子的邻x - h酸性腈，并通过与精心选择的苯胺和酚类直接反应将它们转化为脒和邻苯二甲酸酯。我们想从机理上研究这个重要的反应，特别是它的可逆性。由于目前还没有对氨基类和邻苯二甲酸酯类在h -活化的烷基化反应中进行描述，因此应该在它们作为“经典”导向基团的指导下建立一个定向烷基化反应。作为亲电炔源，炔基（芳基）苯并多洛酮将被使用。这些试剂表现出很高的反应活性，同时又具有台架稳定性和易于操作的特点，已被用于各种引导碳氢活化反应。除了直接的正炔基化外，我们还想开发多米诺型工艺，以获得各种高取代杂环的有效途径。根据我们从最初的机制研究中获得的关于脒和咪酯形成的可逆性以及从烷基化反应中获得的信息，我们最终应该能够开发出一种只使用催化量的邻c - h酸性腈的工艺。在这里，脒类和邻苯二甲酸酯作为tdg在原位生成。此外，我们希望研究这种转化的区域选择性和化学选择性，我们希望能够合理地引导这种选择性。