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

项目描述（由申请人提供）：本研究项目旨在发展形成胺、醚和硫化物的催化合成方法，为新催化剂的设计和推断形成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获得精确的机理信息。所提出的研究重点是几种合成方法，这些方法已被广泛应用，并激发了其他团体发展相关化学。该提案的每个具体目标都集中在开发一个坚固的机械平台上，我们将从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集中于开发用于胺与芳基卤化物偶联的新一代钯催化剂，利用控制催化剂引发的因素、催化循环各个步骤的速率和控制选择性的平衡的数据。该提案的第二部分将建立对铜催化芳基卤化物与氮和氧亲核试剂偶联的机制理解，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集中在最近发现的一种铑催化剂上，这种催化剂有望显著增加烯烃氢胺化的范围。这些研究将使用最新的结构数据来了解这一过程的机制并设计新的催化剂。第四部分的研究将集中在对映选择性方法制备烯丙胺和醚。同样，最近的结构数据将用于理解反应的机制，并设计催化剂，与以前未包含在该过程中的试剂类反应。因此，所提出的研究将显著推进与有机金属催化剂形成碳杂原子键的反应，同时展示利用机理数据设计和开发新的有机金属催化剂的方法，从而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.