Enantioselective Hydroformylation with 3,4-Diazaphospholane Ligands

克拉克教授Landis，威斯康星大学麦迪逊分校化学系由化学系的无机，生物无机和有机化学计划支持，以研究新的过渡金属配体的合成及其在过渡金属催化反应中的应用。 本工作的一个目标是创造新的可延伸的和手性的3，4-二氮磷杂环戊烷配体。 手性3，4-diazaphospholanes使不同的功能基团，创建配体库的合成？酶样的？催化活性过渡金属中心周围的环境。 第二个目标强调应用3，4-二氮杂磷杂环戊烷库来发现用于碳-碳键形成反应的催化剂，例如氢化物，其产生具有高选择性和原子经济性的手性产物。医药中间体是主要目标。理解3，4-二氮磷杂环戊烷配体影响简单底物如苯乙烯和乙酸乙烯酯的对映选择性加氢以产生手性官能化醛的机制构成了第三个目标。 这种机制的研究，使阐明的速率和选择性决定的反应步骤，以及它们是如何受到配体结构的影响。该项目的先进的国家的最先进的对映选择性，过渡金属催化转化，通过设计和合成新的有机膦化合物。 手性过渡金属配合物催化的高效、选择性和原子经济的转化反应是合成手性药物、农药和天然产物的关键技术。 该项目产生的新的氢化物的对映选择性方法将通过提供手性醛的新途径和减少与对映体纯立体中心的生产相关的浪费来广泛影响有机合成。 这项研究为研究生和本科生研究人员提供了广泛的培训和技术技能的发展。 PI和参与该项目的学生将开发新的实践活动，向化学新手学生展示催化的意义和力量。

Professor Clark R. Landis, Department of Chemistry, University of Wisconsin-Madison is supported by the Inorganic, Bioinorganic, and Organometallic Chemistry Program of the Chemistry Division to investigate the synthesis of new transition metal ligands and their applications in transition metal catalyzed reactions. One goal of this work is creation of new extensible and chiral 3,4-diazaphospholane ligands. Chiral 3,4-diazaphospholanes enable the synthesis of ligand libraries with diverse functional groups that create ?enzyme-like? environments around catalytically active transition metal centers. A second goal emphasizes application of 3,4-diazaphospholane-libraries to discover of catalysts for carbon-carbon bond forming reactions, such as hydroformylation, that yield chiral products with high selectivity and atom economy. Pharmaceutical intermediates constitute a major target. Understanding the mechanism by which 3,4-diazaphospholane ligands effect enantioselective hydroformylation of simple substrates such as styrene and vinyl acetate to produce chiral, functionalized aldehydes constitutes a third goal. Such mechanistic studies enable elucidation of the rate- and selectivity-determining reaction steps and how they are influenced by ligand structure.This project advances the state-of-the-art of enantioselective, transition-metal catalyzed transformations through the design and synthesis of novel organophosphine compounds. Efficient, selective, and atom economical transformations catalyzed by chiral transition metal complexes represent a critical technology for the synthesis of chiral pharmaceuticals, agrochemicals, and natural products. New enantioselective processes for hydroformylation resulting from this project will broadly impact organic synthesis by providing new pathways to chiral aldehydes and reducing waste associated with the production of enantiomerically pure stereogenic centers. This research provides graduate and undergraduate researchers with broad training and development of technical skills. The PI and students involved in this project will develop new hands-on activities to demonstrate the meaning and power of catalysis to novice chemistry students.