New Chiral Br??nsted Acids for Asymmetric Synthesis

用于不对称合成的新型手性布朗斯台德酸

• 批准号: 8244446
• 负责人: WILLIAM Dean WULFF
• 金额: $ 26.61万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8244446
• 关键词: Accidents; Acids; Affect; Alcohols; Aldehydes; Alkylation; Amines; Anions; Aziridines; Benzoic Acids; Binding; Boron; Catalysis; Charge; Complex; Computer Simulation; Effectiveness; Equilibrium; Family; Generations; Goals; Hydrogen Bonding; Imines; In Situ; Investigation; Ions; Isotopes; Kinetics; Ligands; Literature; Maps; Mediating; Methods; Oxygen; Phase; Phenols; Process; Reaction; Relative (related person); Reporting; Research; Screening procedure; Solvents; Source; Structure; System; Temperature; Time; Ursidae Family; Variant; Water; Work; catalyst; cycloaddition; design; diazo compound; public health relevance

DESCRIPTION (provided by applicant): The vaulted biaryl ligands VANOL and VAPOL form a unique polyborate anion with a boroxinate core and is beginning to be recognized as a very unique and versatile platform for asymmetric catalysis. As an ion-pair with a protonated imine, this chiral anion will effect the aziridination of imines with diazo compounds with very high yields, diastereoselectivity and enanatioselectivity. Mechanistic investigations including natural abundance kinetic isotope studies will be undertaken to understand how the boroxinate catalyst is formed and how it functions in a variety of reactions including aziridination reactions. The boroxinate core is anionic and has seven oxygens which all bear some of the negative charge and it is possible that it serves as a template in which more than one substrate can H-bond with the boroxinate core at the same time and this helps to determine the transition state. Computations will be persued in an effort to understand how the substrates interact with the boroxinate core in the transition state of the aziridination and other reactions. In addition to the unique structure of this boroxinate catalyst, its utility is greatly enhanced by the fact that it can be assembled by the substrate from the ligand, a boron source, two equivalents of an alcohol or phenol and three equivalents of water. The diverse array of catalysts that can be generated by this process is thus virtually limitless. Investigations will also be carried out to determine the effectiveness of this boroxinate catalyst in other reactions including the Darzens reaction, [3+2] cycloadditions, aminoallylation of aldehydes, and the Ugi reaction. PUBLIC HEALTH RELEVANCE: We have discovered the structure of the catalyst-substrate complex for the catalytic asymmetric aziridination reaction of imines (AZ reaction). With the information gained from this structure, the goals of this proposal are to study the mechanism by which these catalyst react, design new catalyst structures for enhanced reactivities and selectivities and to apply them to other organic reactions.

描述（由申请人提供）：拱形的双子配体Vanol和Vapol形成了带有硼氧蛋白核心的独特多硼酸酯阴离子，并开始被认为是一个非常独特且通用的非对称催化平台。作为具有质子化亚胺的离子对，这种手性阴离子将用具有很高产量，非对映射性和递质选择性的重氮化合物的亚胺作用。将进行包括自然丰度动力学研究在内的机械研究，以了解如何形成硼油蛋白催化剂，以及它如何在包括Aziridination反应在内的各种反应中发挥作用。硼油素芯是阴离子的，具有七个氧气，所有氧气都带有一些负电荷，并且有可能用作模板，其中多个底物可以同时用钢铁芯键键，这有助于确定过渡状态。将对计算进行说明，以了解底物如何在Aziridination和其他反应的过渡状态下与硼砂芯相互作用。除了这种硼油蛋白催化剂的独特结构外，它的效用还可以通过从配体，硼源，两个酒精或苯酚的两个等效物以及三个等效水的底物组装来大大增强其效用。因此，该过程可以生成的各种催化剂几乎是无限的。还将进行研究，以确定该硼油蛋白催化剂在其他反应中的有效性，包括Darzens反应，[3+2]环载条，醛的氨基甲基化和UGI反应。 公共卫生相关性：我们发现了亚胺的催化不对称的无偶合化反应（AZ反应）的催化剂基底络合物的结构（AZ反应）。通过从这种结构中获得的信息，该提案的目标是研究这些催化剂反应的机制，设计新的催化剂结构以增强反应性和选择性，并将其应用于其他有机反应。