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个元素。这种重金属是主要的p块元素中V族的最后一个稳定原子，被称为pnitogen。尽管元素铋的原子量很大，但其毒性却低得令人惊讶。事实上，铋衍生化合物已被用于抗生素、不透射线骨水泥、抗癌剂、治疗胃肠道疾病的药物和许多其他医学应用。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，其中金属分别处于+3和+5氧化态。根据铋(+3，+5)的氧化状态、总电荷(-1，0，+1，+2)和配位元素(3，4，5，6)的数量，有机铋化合物的几何构型有很大的不同。由于三价有机铋是一对孤子，因此可以作为过渡金属络合物中的sigma供体配体。此外，尽管铋具有完整的电子壳层，但有机铋化合物也可以通过与配体形成超价相互作用来充当Lewis酸。由于这些显著和独特的性质，有机铋化合物在全合成、方法学开发、聚合反应以及绿色、有机金属和药物化学中得到了应用。我们小组报道了制备功能化的三芳基、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度官能化的三芳基铋的有效策略，该策略涉及直接对有机金属物种进行三官能团操纵。这些有机铋化合物被用于一系列铜催化的芳基化、烷基化和环丙基化反应，以及钯催化的与芳基/杂芳基、卤化乙烯和三氟代盐的交叉偶联反应。这些方法导致C-C、C-N和C-O键的构建，在温和的条件下操作，表现出高的官能团耐受性，并允许在药物相关的支架上安装官能化基团。*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，允许生物有机化合物的修饰，使新型反应成为可能，并提供合成具有挑战性的分子的途径。我们还将制备具有独特的电子、空间和几何性质的新型有机铋化合物，这些化合物具有增溶基团，导致超价态和手性，并可在催化、电化学、材料科学和构造学中得到应用。该项目非常适合培养在催化、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。