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

描述(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，并获得精确的机理信息，用于设计新的催化剂，并推断形成C-N、C-O和C-S键的新兴催化过程与形成C-C或C-H键的相关催化过程之间的关系。拟议的研究集中在几种已被广泛使用并激励其他团体发展相关化学的合成方法上。这项提议的每个具体目标都集中在开发一个坚实的机械平台，我们将在这个平台上建立新的催化剂和反应过程。拟议研究的一部分将侧重于开发新一代钯催化剂，用于胺与芳基卤化物的偶联，使用控制催化剂启动的因素、催化循环各个步骤的速度以及控制选择性的平衡的数据。提案的第二部分将从机理上理解铜催化的芳基卤化物与氮和氧亲核试剂的偶联，并利用这一信息作为灵感，开发使用其他金属形成芳基碳-杂原子键的催化剂。拟议研究的第三部分将重点放在最近发现的一种有望显著扩大烯烃氢胺作用范围的催化剂上。这些研究将使用最新的结构数据来了解这一过程的机理，并设计新的催化剂。研究的第四部分将集中在对映选择性方法来制备烯丙基胺和醚。同样，最近的结构数据将被用来理解反应的机理，并设计与以前没有包含在这个过程中的试剂类别反应的催化剂。因此，拟议的研究将极大地促进与有机金属催化剂的反应，以形成具有重要药用价值的材料中的碳-杂原子键，同时展示在设计和开发新的有机金属催化剂时使用机理数据的方法，以提高有机合成的效率、多样性和能力。

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.