Metal-Catalyzed Asymmetric Synthesis of P-C and P-P Bonds

化学催化计划支持教授大卫S。Glueck在达特茅斯学院，研究通过金属催化的P-碳（C）和P-P键的不对称合成制备手性磷（P）-立体膦的新方法。 手性膦可用于不对称催化，其通常用于制药工业以制备单一对映体药物。 然而，由于缺乏通用的合成方法，β-立体异构手性配体的发展相对缓慢。该项目进一步发展了金属催化的P-C键的立体控制形成，这是解决这一问题的一种新的和潜在有用的方法，并研究了类似的过程，使P-P键，这是几乎未开发的。 在这两种情况下，含有两个由连接基（*P~P* 或 *P~C*）分开的立体中心的仲膦底物已经被设计成使得这些原子与催化剂之间的相互作用导致比单独催化剂所强制的选择性更高的选择性（正协同性）。 所得到的P-立体膦和二膦是潜在的有用的建筑块为其他P-立体膦，而独特的立体电子性质的膦配体也正在调查中。 相关的研究利用了新的底物来源于廉价的天然存在的手性化合物，使立体控制使用非手性催化剂，并调查了一种不寻常的方法，用于筛选外消旋催化剂，以制备C2-对称的双（膦）和罕见的C3-对称的三膦。该项目发展了对金属催化形成磷-碳和磷-磷键以及新的手性膦的更好的理解，这些手性膦是不对称催化中有价值的配体，在制药工业中具有潜在的应用。正协同效应的研究在均相催化中有着广泛的应用。 研究生和本科生接受无机，有机金属和有机化合物的合成和表征，反应机理研究和催化方面的培训。 学生们有机会向其他科学家和公众展示他们的工作。研究结果在出版物和会议报告中广泛传播，并被纳入达特茅斯的课程和外联报告。该项目继续扩大代表性不足的群体，特别是妇女和美洲土著人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 research on new methods to prepare chiral phosphorus (P)-stereogenic phosphines via metal-catalyzed asymmetric synthesis of P-carbon (C) and P-P bonds. Chiral phosphines are useful in asymmetric catalysis, which is commonly employed in the pharmaceutical industry to make single-enantiomer drugs. However, the development of P-stereogenic chiral ligands has been relatively slow because of a lack of general synthetic methods. This project further develops the metal-catalyzed stereocontrolled formation of P-C bonds, a new and potentially useful approach to this problem, and investigates analogous processes to make P-P bonds, which are virtually unexplored. In both cases, secondary phosphine substrates containing two stereocenters separated by a linker (*P~P* or *P~C*) have been designed so that interactions between these atoms and the catalyst result in selectivity higher than that enforced by the catalyst alone (positive cooperativity). The resulting P-stereogenic phosphiranes and diphosphines are potentially useful building blocks for other P-stereogenic phosphines, while the unique stereoelectronic properties of phosphirane ligands are also under investigation. Related studies take advantage of new substrates derived from cheap naturally occurring chiral compounds, enabling stereocontrol using achiral catalysts, and investigating an unusual method for screening racemic catalysts to prepare C2-symmetric bis(phosphines) and rare C3-symmetric triphosphines. This project develops a better understanding of metal-catalyzed formation of phosphorus-carbon and phosphorus-phosphorus bonds and new chiral phosphines, valuable ligands in asymmetric catalysis with potential applications in the pharmaceutical industry. Studies of positive cooperativity are broadly useful in homogeneous catalysis. Graduate and undergraduate students receive training in the synthesis and characterization of inorganic, organometallic, and organic compounds, mechanistic studies of their reactions, and in catalysis. The students have opportunities to present their work to other scientists and to the public. The results are disseminated broadly in publications and conference presentations, and they are integrated into Dartmouth courses and outreach presentations. This project continues to broaden the participation of underrepresented groups, especially women and Native Americans, in research at the graduate and undergraduate levels.