GOALI: CAS: Iron-Catalyzed Suzuki-Miyaura Cross Coupling Using Pseudohalide Alkyl Electrophiles

目标：CAS：使用拟卤化物烷基亲电子试剂的铁催化 Suzuki-Miyaura 交叉偶联

• 批准号: 2154928
• 负责人: Dunwei Wang
• 金额: $ 49.8万
• 依托单位: Boston College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2154928&HistoricalAwards=false
• 关键词: GOALI; CAS; Iron; Catalyzed; Suzuki

With the support of the Chemical Catalysis program in the Division of Chemistry, Professor Jeffery Byers of Boston College, in close collaboration with partners at the Sanofi pharmaceutical company, is studying a new method to assemble complex molecules with relevance to the pharmaceutical industry. The new method involves readily available raw materials and more abundant, iron-based catalysts in contracts to the precious metal-based catalysts, typically palladium-based, that are almost always used for the targeted reactions. Additionally, the method provides greater control over the three-dimensional structure of the product molecules, a critically important characteristic desired in most drugs. To complement the scientific goals of the proposal, the partnership between Boston College and Sanofi will be leveraged to educate the general public about the values of sustainable chemistry and its role in the pharmaceutical industry through town hall meetings and student visits to Sanofi.Under this GOALI award, the Byers research group at Boston College and their collaborators at Sanofi Pharma will work to develop Suzuki-Miyaura cross-coupling reactions of alkyl pseudo-halides with aryl boronic and alkyl boronic esters and/or boranes catalyzed by iron-based complexes. The Suzuki-Miyaura cross coupling reaction is one of the most widely used C–C bond-forming reactions in academic and industrial chemistry. However, palladium-based catalysts have limited reactivity with sp3-hybridized substrates, which has resulted in an over-representation of flat molecules being investigated as therapeutic candidate molecules in pharmaceutical chemistry circles. It is hoped that by introducing Fe-based catalysts, a wider array of sp3-hybridized substrates will be accessible. Replacing the alkyl halide electrophile in these reactions with alkyl pseudo-halides is expected to have significant impact in the pharmaceutical industry as alkyl pseudo-halides are conveniently prepared from alcohols, which, due to their stability and low toxicity, are well represented in compound libraries in the pharmaceutical industry. The project will take advantage of the high and medium throughput instrumentation that is at Sanofi for the development of aryl-alkyl and alkyl-alkyl cross coupling reactions and enantioselective and/or enantiospecific cross coupling reactions. Moreover, in situ monitoring of reactions will facilitate in depth mechanistic investigations, which are lacking in the field of iron-catalyzed cross-coupling reactions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学催化计划的化学系的支持下，波士顿学院的杰弗里·拜尔斯教授与赛诺菲制药公司的合作伙伴密切合作，正在研究一种新的方法，以与制药行业相关。新方法涉及与珍贵金属基催化剂合同（通常是基于钯的基于钯的催化剂的合同）中更丰富的，基于铁的催化剂，这些催化剂几乎总是用于靶向反应。此外，该方法可以更大地控制产物分子的三维结构，这是大多数药物所需的至关重要的特征。为了完成提案的科学目标，波士顿学院和萨诺菲之间的伙伴关系将被利用，以教育公众通过市政厅会议和学生访问来教育可持续化学的价值及其在制药行业中的作用。伪卤化物用芳基硼酸和烷基硼酯和/或由铁基络合物催化的硼烷。 Suzuki-Miyaura交叉耦合反应是学术和工业化学中使用最广泛的CC键形成反应之一。然而，钯基催化剂对SP3杂交底物的反应性有限，这导致在药物化学圆圈中研究为治疗性候选分子的扁平分子的过度代表。希望通过引入基于FE的催化剂，可以访问各种SP3杂交底物。在这些反应中，与烷基伪卤化物的这些反应取代烷基​​卤化物电力，预计将对制药行业产生重大影响，因为烷基假卤化物是通过酒精方便地制备的，由于醇的稳定性和低毒性，在制药工业的化合物中具有很好的代表性。该项目将利用Sanofi的高和中等吞吐量仪器，用于开发芳基 - 烷基和烷基烷基交叉耦合反应以及对映选择性和/或对映异义的交叉耦合反应。此外，对反应的原位监测将有助于深度机械研究，而铁催化的交叉偶联反应领域缺乏。该奖项反映了NSF的法定任务，并通过使用基金会的知识分子优点和更广泛的影响审查标准来评估被认为是宝贵的支持。