Metal-Catalyzed Asymmetric Synthesis of P-Stereogenic Phosphines

化学催化计划支持达特茅斯学院的大卫·S·格鲁克教授的一个项目，该项目描述了最近报道的一种新反应--铂催化的不对称磷化反应的进一步发展计划。该计划旨在了解手性金属催化剂将外消旋二次膦PHR(R‘)与苯基卤化物ArCH2X偶联，通过金属介导的磷立体控制得到对映体丰富的叔膦PR(R’)(CH2Ar)的过程。由于缺乏通用的合成方法，这类手性手性配体的发展相对缓慢。不对称磷化反应是解决这一问题的一种新的、有潜力的方法。该反应将被应用于新型C2对称双齿双膦的不对称合成(工业上最常见的配体类)和类似的C3对称三齿三膦的不对称合成，这几乎是未知的。在这两种情况下，催化剂控制可能会导致不对称放大和目标产物中非常高的对映体过剩，这可能会从不需要的非对映异构体中分离出来。手性膦在不对称催化中特别有用，在制药工业中，手性膦通常用于制造单一对映体药物。在国家科学基金化学部化学催化计划的支持下，David S.Glueck教授将更好地理解金属催化的不对称磷化反应和新型手性膦，这两种配体在不对称催化中具有潜在的应用价值。研究催化剂和底物的选择性控制以及催化剂对称性对手性识别和反应活性的影响将在均相催化中得到广泛的应用。研究生和本科生将接受无机、有机金属和有机化合物的合成和表征、反应的机理研究和催化方面的培训，并将有机会向其他科学家和公众展示他们的工作。结果将在出版物和会议发言中广泛传播。他们将被整合到达特茅斯大学的课程中，并在向当地中学生的演讲中使用。该项目还将继续扩大任职人数不足的群体，特别是妇女参与研究生和本科生研究的范围。

The Chemical Catalysis Program supports Professor David S. Glueck at Dartmouth College for a project that describes a plan for further development of a recently reported new reaction, platinum-catalyzed asymmetric phosphination. The plan is to understand the process in which a chiral metal catalyst couples a racemic secondary phosphine PHR(R') with a benzyl halide ArCH2X to give an enantioenriched tertiary phosphine PR(R')(CH2Ar) via metal-mediated stereocontrol at phosphorus. The development of such P-stereogenic chiral ligands has been relatively slow because of a lack of general synthetic methods. Asymmetric phosphination is a new and potentially useful approach to this problem. This reaction will be applied to the asymmetric synthesis of novel C2-symmetric bidentate diphosphines (the most common ligand class for industrial applications) and to analogous C3-symmetric tridentate triphosphines, which are virtually unexplored. In both cases, catalyst control may lead to asymmetric amplification and very high enantiomeric excess in the desired product, which may be separated from unwanted diastereomers. Chiral phosphines are particularly useful in asymmetric catalysis, which is commonly employed in the pharmaceutical industry to make single-enantiomer drugs.With the support of the Chemical Catalysis Program in the Chemistry Division at the National Science Foundation, Professor David S. Glueck will develop a better understanding of metal-catalyzed asymmetric phosphination and new chiral phosphines, valuable ligands in asymmetric catalysis that have potential applications in the pharmaceutical industry. Studies of catalyst and substrate control of selectivity and the effect of catalyst symmetry on chiral recognition and reactivity will be broadly useful in homogeneous catalysis. Graduate and undergraduate students will receive training in synthesis and characterization of inorganic, organometallic, and organic compounds, mechanistic studies of their reactions, and in catalysis, and will have an opportunity to present their work to other scientists and to the public. The results will be disseminated broadly in publications and conference presentations. They will be integrated into Dartmouth courses and in presentations to local middle school students. This project will also continue to broaden the participation of underrepresented groups, especially women, in research at the graduate and undergraduate levels.