RATIONAL DESIGN OF CATALYSTS FOR C-C BOND FORMATION

C-C 键形成催化剂的合理设计

• 批准号: 6519916
• 负责人: John F Hartwig
• 金额: $ 32.34万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6519916
• 关键词: alkyl group; catalyst; chemical kinetics; chemical synthesis; covalent bond; ligands; phosphines

My group recently discovered a new class of C-C bond-forming reaction: the direct alpha-arylation of ketones catalyzed by palladium complexes. We have now extended this reaction to include the alpha-arylation of carboxylic acid derivatives such as amides and malonates, while finding remarkable catalysts that provide alpha-arylation of ketones at room temperature using aryl bromides and at only 70 C using aryl chlorides. Under NIH support my group would 1) study new alkylphosphine ligands for the catalytic process based on our hypothesis that sterically hindered, chelating alkyl phosphines accelerate reaction rates, 2) expand the scope of this new process to other types of carbonyl compounds, alkyl cyanides, and nitroalkanes and 3) develop a detailed, quantitative mechanistic understanding of the reactions comprising the catalytic cycle. More specifically, we will prepare alkylphosphine ligands containing large and small substituents at phosphorus and with backbones that provide large and small bite angles. These ligands will be used to further improve yields, rates, and substrate scope, while uncovering the features of our current ligands that provide such fast rates. These ligands will also be used in studies toward extending the scope of electrophiles to vinyl and heteroaromatic halides and sulfonates, and to nucleophilic partners such as the anions of alpha-diketones, alpha-siloxy ketones, alpha, beta-unsaturated ketones, beta-dicarbonyl compounds, esters, nitriles, nitroalkanes, and azlactones. A detailed mechanistic description of the catalytic chemistry based on firm quantitative data is an important goal of the proposed research. In general, we will conduct a careful study to determine how ligands steric and electronic properties affect each step of the catalytic cycle, including oxidative addition of aryl halide that is likely to be the rate determining step of the reaction, formation of an arylpalladium enolate complex from the resulting arylpalladium halide complex, and C-C bond-forming reductive elimination that is the crucial coupling step in the catalytic cycle. We have conducted the first direct observation of this type of reductive elimination. Beta-Hydrogen elimination from the palladium enolate complexes, which competes with reductive elimination, will be investigated to determine how this process can be prevented. Finally, we will begin a detailed mechanistic study of the initial asymmetric version of the ketone arylation process in conjunction with Buchwald's synthetic effort as a means for our two groups to create improved enantioselective catalysts.

我的小组最近发现了一种新的C-C键形成反应：由钯配合物催化的酮的直接α-酰化。 现在，我们已经扩展了这种反应，以包括羧酸衍生物（如酰胺和丙二酸酯）的α-酰化，同时发现了出色的催化剂，这些催化剂可在室温下使用芳基溴化物在室温下和使用芳基氯的70 c在室温下α-溶解酮。 在NIH支持下，我的小组将1）基于我们的假设研究新的烷基膦配体进行催化过程，即在空间上受到阻碍，螯合烷基膦加速反应速率，2）将这种新过程的范围扩展到其他类型的羰基化合物，烷基氰化物和硝基烷的其他类型的序列，并逐渐融合了一个序列的反应性。更具体地说，我们将制备含磷的大小化取代基的烷基膦配体，并具有提供大小咬合角的骨架。 这些配体将用于进一步提高产量，速率和底物范围，同时发现我们当前提供如此快速速率的配体的特征。 These ligands will also be used in studies toward extending the scope of electrophiles to vinyl and heteroaromatic halides and sulfonates, and to nucleophilic partners such as the anions of alpha-diketones, alpha-siloxy ketones, alpha, beta-unsaturated ketones, beta-dicarbonyl compounds, esters, nitriles, nitroalkanes, and azlactones。基于公司定量数据的催化化学的详细机械描述是拟议研究的重要目标。 In general, we will conduct a careful study to determine how ligands steric and electronic properties affect each step of the catalytic cycle, including oxidative addition of aryl halide that is likely to be the rate determining step of the reaction, formation of an arylpalladium enolate complex from the resulting arylpalladium halide complex, and C-C bond-forming reductive elimination that is the crucial coupling step in the catalytic cycle. 我们已经对这种还原性消除进行了首次直接观察。 将研究如何与还原性消除竞争的钯烯丙基复合物中消除β-氢化剂，以确定如何预防该过程。 最后，我们将与布赫瓦尔德（Buchwald）的合成努力一起开始对酮芳基化过程的初始不对称版本进行详细的机械研究，这是我们两组创建改进的对映选择性催化剂的一种手段。