Expanding the Scope of Organobismuth Compounds in Organic Synthesis

扩大有机铋化合物在有机合成中的应用范围

• 批准号: RGPIN-2017-05605
• 负责人: Gagnon, Alexandre
• 金额: $ 1.6万
• 依托单位: Université du Québec à Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=651342
• 关键词: Expanding; Scope; Organobismuth; Compounds; Organic

Bismuth is the 83rd element of the Periodic Table. This heavy metal is the last stable atom of group V of the main p block elements, called the pnictogens. Despite its heavy atomic weight, elemental bismuth shows surprisingly low toxicity. In fact, bismuth-derived compounds have been used as antibiotics, radiopaque bone cements, anticancer agents, drugs for the treatment of gastrointestinal disorders and in many other medicinal applications.******Organobismuth compounds, a class of organometallic reagents that contain a C-Bi bond, are subdivided into two main groups: trivalent and pentavalent organobismuthines where the metal is in the +3 and +5 oxidation state, respectively. A wide diversity of geometries have been found for organobismuth compounds depending on the oxidation state of bismuth (+3, +5), its overall charge (-1, 0, +1, +2) and its number of coordinated elements (3, 4, 5, 6). Due to its lone pair, trivalent organobismuthines can act as sigma-donor ligands in transition metal complexes. In addition, even though bismuth has a full electronic shell, organobismuth compounds can also act as Lewis acids by forming hypervalent interactions with ligands. Due to these remarkable and unique properties, organobismuth compounds have found applications in total synthesis, methodology development, polymerization reactions as well as in 'green', organometallic and medicinal chemistry.******Our group reported protocols to prepare functionalized triaryl, trialkyl and tricyclopropylbismuthines. In particular, we developed an efficient strategy for the synthesis of highly functionalized triarylbismuthines that involves direct triple functional group manipulation directly on the organometallic species. These organobismuth compounds were used in a portfolio of copper-catalyzed arylation, alkylation and cyclopropylation reactions as well as in palladium-catalyzed cross-coupling reactions with aryl/heteroaryl and vinyl halides and triflates. These methods, which lead to the construction of C-C, C-N and C-O bonds, operate under mild conditions, show high functional group tolerance and allow the installation of functionalized groups on medicinally relevant scaffolds.******In this research program, we propose to use the unique properties of organobismuth compounds to develop novel reactions that allow the modification of bioorganic compounds, enable new types of reactions, and give access to synthetically challenging molecules. We will also prepare novel organobismuth compounds that have unique electronic, steric and geometric properties, that possess solubilizing groups, that lead to hypervalency and chirality, and that can find applications in catalysis, electrochemistry, material sciences and tectonics. This program is ideally suited for training highly qualified personnel with multidisciplinary skills in the field of catalysis, organic, organometallic and green chemistry.

铋是元素周期表中的第 83 号元素。这种重金属是主要 p 区元素 V 族的最后一个稳定原子，称为磷元素。尽管元素铋的原子量很大，但其毒性却出人意料地低。事实上，铋衍生化合物已被用作抗生素、不透射线骨水泥、抗癌剂、治疗胃肠道疾病的药物以及许多其他医学应用。 *****有机铋化合物是一类含有 C-Bi 键的有机金属试剂，主要分为两大类：三价和五价有机铋，其中金属位于 分别为+3和+5氧化态。有机铋化合物的几何形状多种多样，具体取决于铋的氧化态（+3、+5）、总电荷（-1、0、+1、+2）及其配位元素数量（3、4、5、6）。由于其孤对电子，三价有机铋可以作为过渡金属配合物中的σ供体配体。此外，尽管铋具有完整的电子壳层，有机铋化合物也可以通过与配体形成超价相互作用而充当路易斯酸。由于这些显着而独特的性质，有机铋化合物已在全合成、方法开发、聚合反应以及“绿色”、有机金属和药物化学中得到应用。******我们小组报告了制备官能化三芳基、三烷基和三环丙基铋的方案。特别是，我们开发了一种合成高官能化三芳基铋的有效策略，该策略涉及直接对有机金属物质进行直接三官能团操作。这些有机铋化合物用于铜催化的芳基化、烷基化和环丙基化反应，以及钯催化的与芳基/杂芳基以及乙烯基卤化物和三氟甲磺酸酯的交叉偶联反应。这些方法可构建 C-C、C-N 和 C-O 键，在温和条件下操作，显示出高官能团耐受性，并允许在医学相关支架上安装官能团。******在本研究计划中，我们建议利用有机铋化合物的独特性质来开发新的反应，从而可以修饰生物有机化合物，实现新型反应，并提供 具有合成挑战性的分子。我们还将制备新型有机铋化合物，这些化合物具有独特的电子、空间和几何特性，具有增溶基团，可产生超价和手性，并且可以在催化、电化学、材料科学和构造学中找到应用。该项目非常适合培养催化、有机、有机金属和绿色化学领域具有多学科技能的高素质人才。