Metal-Catalyzed Asymmetric Synthesis of P-Stereogenic Phosphines

金属催化不对称合成对立构膦

• 批准号: 1011887
• 负责人: David Glueck
• 金额: $ 45万
• 依托单位: Dartmouth College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1011887&HistoricalAwards=false
• 关键词: Metal; Catalyzed; Asymmetric; Synthesis; Stereogenic

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.

化学催化计划支持教授大卫S。Glueck在达特茅斯学院的一个项目，描述了一个计划，进一步发展最近报道的新反应，铂催化的不对称膦化。 该计划是为了了解手性金属催化剂通过金属介导的磷的立体控制将外消旋仲膦PHR（R '）与苄基卤ArCH 2X偶联以得到对映体富集的叔膦PR（R'）（CH 2Ar）的过程。由于缺乏通用的合成方法，这类β-立体异构手性配体的发展相对缓慢。不对称膦化反应是解决这一问题的一种新的和潜在有用的方法。该反应将被应用于新型C2-对称二齿二膦（工业应用中最常见的配体类）和类似的C3-对称三齿三膦，这是几乎未开发的不对称合成。在这两种情况下，催化剂控制可导致所需产物的不对称扩增和非常高的对映体过量，所需产物可与不需要的非对映体分离。手性膦在不对称催化中特别有用，不对称催化通常用于制药工业以制备单一对映体药物。Glueck将更好地理解金属催化的不对称膦化和新的手性膦，在制药工业中具有潜在应用的不对称催化中有价值的配体。研究催化剂和底物对选择性的控制以及催化剂对称性对手性识别和反应活性的影响，在均相催化中具有广泛的应用前景。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。研究结果将在出版物和会议报告中广泛传播。他们将被纳入达特茅斯的课程和对当地中学生的演讲中。该项目还将继续扩大代表性不足的群体，特别是妇女参与研究生和本科生一级的研究。

项目成果

Rhodium-Catalyzed Asymmetric Dehydrocoupling: Enantioselective Synthesis of a P-Stereogenic Diphospholane with Mistake-Correcting Diastereoselectivity

铑催化的不对称脱氢偶联：具有纠错非对映选择性的对映体二磷烷的对映选择性合成

• DOI: 10.1021/acs.organomet.3c00188
• 发表时间: 2023
• 期刊: Organometallics
• 影响因子: 2.8
• 作者: Chachula, Sarah T.;Scheetz, Perry M.;Zureick, Andrew H.;Hughes, Russell P.;Glueck, David S.;Hernandez, Ritchie E.;Figueroa, Joshua S.;Rheingold, Arnold L.
• 通讯作者: Rheingold, Arnold L.

Configurational Lability at Tetrahedral Phosphorus: syn/anti ‐Isomerization of a P‐Stereogenic Phosphiranium Cation by Intramolecular Epimerization at Phosphorus

四面体磷的构型不稳定性：通过磷分子内差向异构化实现 P-立体磷鎓阳离子的顺/反异构化

• DOI: 10.1002/anie.202110753
• 发表时间: 2022
• 期刊: Angewandte Chemie International Edition
• 作者: Tipker, Ryan M.;Muldoon, Jake A.;Pham, Daniel H.;Varga, Balazs R.;Hughes, Russell P.;Glueck, David S.;Balaich, Gary J.;Rheingold, Arnold L.
• 通讯作者: Rheingold, Arnold L.