GOALI: Catalytic Stereoselective Cross-Coupling Reactions

在化学系化学催化项目的支持下，波士顿学院的James Morken教授和辉瑞公司的Robert Singer博士正在研究开发新的化学反应，以产生具有明确定义的三维拓扑结构的分子。由于新批准的药物中存在很大一部分具有确定的三维形状的分子（2015年占新药的44%），因此能够控制这种富含sp3的拓扑结构的化学反应对制药和化学工业非常有价值。这项研究的目标是开发这种反应，期望这些过程将简化药物开发并改善获得重要药物的途径。这个学术-工业合作伙伴关系正在研究新的钯和铜基反应，因为它们有能力作为有效的催化剂来控制产品的三维拓扑结构。他们还在评估这些催化剂是否能够高效、经济地运行，并尽量减少有害废物的产生。通过GOALI（与工业界学术联络的资助机会）奖，参与研究的本科生和研究生将获得对医学、制药和化学等领域的科学职业至关重要的培训。根据这项GOALI奖，波士顿学院的Morken研究小组和辉瑞公司的Robert Singer博士领导的合作者正在开发在中介二硼烷底物上进行的对映选择性交叉偶联反应。手性催化剂正在开发中，它可以影响交叉偶联反应，选择性地破坏二硼基反应物的对称性，并产生保留原始硼酯基之一的产物。除了设计合适的反应和检查它们的合成效用外，该团队还在开发新的手性膦配体的简明路线，预计这种配体不仅在二硼烷反应中有用，而且在其他催化转化中也有用。此外，机理实验正在进行，以确定为什么二硼基底物在交叉偶联反应中异常活跃，以及所获得的信息是否可以用于设计新的反应。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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 James Morken of Boston College and Dr. Robert Singer of Pfizer are studying the development of new chemical reactions that produce molecules having a well-defined three-dimensional topology. Because a significant fraction of molecules having a defined three-dimensional shape are present in newly approved drugs (44% of new pharmaceuticals in 2015), chemical reactions that can control this sp3-rich topology are valuable to the pharmaceutical and chemical industries. The goal of this research is to develop such reactions with the expectation that these processes will streamline drug-development and improve access to important medicines. This academic-industrial partnership is studying new palladium and copper-based reactions for their ability to act as effective catalysts to control the three dimensional topology of the product. They are also evaluating whether these catalysts can operate efficiently, economically, and with minimal production of hazardous waste. By being part of the collaboration through the GOALI (grant opportunities for academic liaison with industry) award, the undergraduate and graduate students involved in the research will acquire training that is critical to science-based careers in fields ranging from medicine to pharmaceuticals, and to chemistry. Under this GOALI award, the Morken research group at Boston College and collaborators led by Dr. Robert Singer at Pfizer are developing enantioselective cross-coupling reactions that operate on meso-diborylalkane substrates. Chiral catalysts are being developed that can affect cross-coupling reactions that selectively break the symmetry of the diboryl reactant and deliver products that retain one of the original boronic ester groups. In addition to the design of appropriate reactions and the examination of their synthetic utility, the team is developing concise routes to new chiral phosphine ligands that are expected to not only be useful in the the diborylalkane reactions but also in other catalytic transformations. Additionally, mechanistic experiments are being carried out to determine why diboryl substrates are unusually reactive in cross-coupling reactions and whether the gained information can be used in the design of new 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.