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

在化学系化学催化项目的支持下，波士顿学院的Jeffery Byers教授与赛诺菲制药公司的合作伙伴密切合作，正在研究一种组装与制药行业相关的复杂分子的新方法。新方法涉及到容易获得的原材料和更丰富的铁基催化剂，而贵金属基催化剂通常是钯基催化剂，几乎总是用于目标反应。此外，该方法对产品分子的三维结构提供了更好的控制，这是大多数药物所希望的一个至关重要的特征。为了实现该提议的科学目标，波士顿学院和赛诺菲之间的合作伙伴关系将通过市政厅会议和学生访问赛诺菲来教育公众可持续化学的价值及其在制药行业中的作用。在这一目标奖下，波士顿学院的拜尔斯研究小组和他们在赛诺菲制药公司的合作者将致力于开发烷基拟卤化物与芳基硼酸酯和烷基硼酸酯和/或铁基络合物催化的硼烷的铃木-宫浦交叉偶联反应。Suzuki-Miyaura交叉偶联反应是学术和工业化学中应用最广泛的C-C成键反应之一。然而，钯基催化剂与SP3杂化底物的反应活性有限，这导致了平板分子在药物化学界被研究为治疗候选分子的过度表现。人们希望通过引入铁基催化剂，可以获得更广泛的SP3杂化底物。在这些反应中用烷基拟卤化物取代烷基卤化物亲电试剂有望在制药工业中产生重大影响，因为烷基拟卤化物可以方便地从醇中制备，由于其稳定性和低毒性，在制药工业的化合物库中得到了很好的代表。该项目将利用赛诺菲的高通量和中通量仪器，开发芳基-烷基和烷基-烷基交叉偶联反应以及对映体选择性和/或对映体特异性交叉偶联反应。此外，对反应的现场监测将有助于深入的机械调查，这在铁催化的交叉偶联反应领域是缺乏的。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.