Enantioselective Hydroformylation with 3,4-Diazaphospholane Ligands

Clark R. Landis教授，威斯康星大学麦迪逊分校化学系，由化学系无机、生物无机和有机金属化学项目资助，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。这项工作的一个目标是创造新的可扩展的手性3,4-二氮磷烷配体。手性3,4-二氮磷烷能够合成具有不同官能团的配体文库，从而产生“类酶”。催化活性过渡金属中心周围的环境。第二个目标是强调3,4-二氮磷烷库的应用，以发现碳-碳键形成反应的催化剂，如氢甲酰化，产生具有高选择性和原子经济性的手性产物。医药中间体是一个主要目标。第三个目标是了解3,4-二氮磷烷配体对简单底物（如苯乙烯和醋酸乙烯）进行对映选择性氢甲酰化以产生手性功能化醛的机制。这种机理研究能够阐明决定反应速率和选择性的步骤，以及它们如何受到配体结构的影响。该项目通过设计和合成新型有机膦化合物，推进了对映选择性过渡金属催化转化的最新进展。手性过渡金属配合物催化的高效、选择性和原子经济性转化是手性药物、农用化学品和天然产物合成的关键技术。该项目产生的新的氢甲酰化对映选择性过程将通过提供手性醛的新途径和减少与生产对映体纯立体中心相关的浪费，广泛影响有机合成。这项研究为研究生和本科生的研究人员提供了广泛的培训和技术技能的发展。项目负责人和参与该项目的学生将开发新的实践活动，向化学新手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.