Mechanism and Development of Catalysts for the Synthesis of Amines, Ethers, and S

胺、醚、S合成催化剂的机理及研究进展

基本信息

批准号：
7746455
负责人：
John F Hartwig
金额：
$ 44.67万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-02-01 至 2014-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7746455
关键词：
Acids Adopted Air Alcohols Alkanesulfonates Alkenes Amides Amination Amines Ammonia Anti-Inflammatory Agents Anti-inflammatory Antihypertensive Agents Aromatic Amines Azoles Biological Factors Breathing Carbamates Carbohydrate Chemistry Carbon Chemistry Chloride Ion Chlorides Complex Copper Coupling Data Development Drug Discovery Groups Electrons Equilibrium Esters Ethers Experimental Designs Foundations Future Generations Grant Health High Density Lipoproteins Human Hydrogen Hydrogen Bonding Imidates Individual Iridium Kinetics Lanthanoid Series Elements Lead Ligands Metals Methodology Methods Modification Nitrogen Nucleic Acids Organic Synthesis Organometallic Chemistry Oxygen Palladium Pathway interactions Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacologic Substance Process Publishing Reaction Reagent Reflux Relative (related person)Research Research Support Rest Rhodium Roentgen Rays Route Series Sertraline Sulfhydryl Compounds Sulfides Sulfur System Temperature Vertebral column Work Zoloft aryl halide base catalyst design drug candidate drug discovery functional group improved innovation insight meetings next generation piperidine programs public health relevance research study tool torcetrapib

Acids Adopted Air Alcohols Alkanesulfonates Alkenes Amides Amination Amines Ammonia Anti-Inflammatory Agents Anti-inflammatory Antihypertensive Agents Aromatic Amines Azoles Biological Factors Breathing Carbamates Carbohydrate Chemistry Carbon Chemistry Chloride Ion Chlorides Complex Copper Coupling Data Development Drug Discovery Groups Electrons Equilibrium Esters Ethers Experimental Designs Foundations Future Generations Grant Health High Density Lipoproteins Human Hydrogen Hydrogen Bonding Imidates Individual Iridium Kinetics Lanthanoid Series Elements Lead Ligands Metals Methodology Methods Modification Nitrogen Nucleic Acids Organic Synthesis Organometallic Chemistry Oxygen Palladium Pathway interactions Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacologic Substance Process Publishing Reaction Reagent Reflux Relative (related person)Research Research Support Rest Rhodium Roentgen Rays Route Series Sertraline Sulfhydryl Compounds Sulfides Sulfur System Temperature Vertebral column Work Zoloft aryl halide base catalyst design drug candidate drug discovery functional group improved innovation insight meetings next generation piperidine programs public health relevance research study tool torcetrapib

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项目摘要

DESCRIPTION (provided by applicant): This research program aims to develop catalytic synthetic methods that form amines, ethers and sulfides and to obtain precise mechanistic information for the design of new catalysts and for deducing relationships between emerging catalytic processes that form C-N, C-O and C-S bonds and related catalytic processes that form C-C or C-H bonds. The proposed research focuses on several synthetic methods that have become widely utilized and that have inspired other groups to develop related chemistry. Each of the specific aims of this proposal focuses on developing a firm mechanistic platform from which we will build new catalysts and reaction processes. One portion of the proposed research will focus on the development of a new generation of palladium catalysts for the coupling of amines with aryl halides using data on the factors that control catalyst initiation, the rates of individual steps of the catalytic cycle, and equilibria that control selectivity. A second portion of the proposal will establish a mechanistic understanding of copper-catalyzed couplings of aryl halides with nitrogen and oxygen nucleophiles and the use of this information as inspiration to develop catalysts for the formation of aryl carbon-heteroatom bonds using other metals. A third portion of the proposed research will focus on a recently discovered type of rhodium catalyst that promises to significantly increase the scope of alkene hydroaminations. These studies will use recent structural data to understand the mechanism of this process and to design new catalysts. A fourth portion of the research will focus on enantioselective methods to prepare allylic amines and ethers. Again, recent structural data will be used to understand the mechanism of the reaction and to design catalysts that react with classes of reagents that have not been encompassed by this process previously. Thus, the proposed research will significantly advance reactions with organometallic catalysts to form the carbon-heteroatom bonds in pharmaceutically important materials, while demonstrating approaches to use mechanistic data in the design and development of new organometallic catalysts that increase the efficiency, diversity and capability of organic synthesis. PUBLIC HEALTH RELEVANCE: Some of the catalysts that have resulted from this project dramatically improve methods to prepare pharmaceutical intermediates and new catalysts that will result from the proposed research promise to be equally important for the synthesis of these and other biologically active materials. Thus, successful development of the proposed research will significantly increase the accessibility of compounds that improve human health.

描述（由申请人提供）：该研究计划旨在开发形成胺，醚和硫化物的催化合成方法，并获得用于设计新催化剂的精确机理信息，并在形成C-N，C-O和C-S-S-S-S键和相关的催化过程的新兴催化过程之间的关系，以形成C-C-C-C-C-C-C-C-C-C-C-h键。拟议的研究重点是几种已广泛使用的合成方法，并激发了其他群体发展相关化学的方法。该提案的每个具体目的都集中在开发一个公司机械平台上，我们将从中构建新的催化剂和反应过程。拟议的研究的一部分将着重于开发新一代的钯催化剂，以使用控制催化剂启动的因素，催化周期的单个步骤的速率以及控制选择性的均衡的因素，以将胺与芳基卤化物耦合。该提案的第二部分将建立对芳基卤化物与氮和氧亲核试剂的铜催化耦合的机械理解，并使用此信息作为灵感来开发催化剂，以形成使用其他金属形成芳基碳杂质素键。拟议的研究的第三部分将集中在最近发现的犀牛催化剂类型上，该仇恨催化剂有望显着增加烯烃氢化剂的范围。这些研究将使用最新的结构数据来了解此过程的机制并设计新的催化剂。研究的第四部分将重点介绍对照式氨基胺和醚的对照选择方法。同样，最新的结构数据将用于了解反应的机制，并设计与以前未被此过程所包含的试剂类别反应的催化剂。因此，拟议的研究将显着推动与有机金属催化剂的反应，以在药物上重要的材料中形成碳杂质素键，同时展示在新的有机金属催化剂的设计和开发中使用机械数据的方法，从而提高了有机合成的效率，多样性和能力。公共卫生相关性：该项目产生的一些催化剂极大地改善了制备药物中间体和新催化剂的方法，这些方法将由拟议的研究承诺所造成的新催化剂对于合成这些和其他具有生物活性材料同样重要。因此，拟议研究的成功发展将显着提高改善人类健康的化合物的可及性。