C-O and C-N Bond Formation Using Metal-Based Reagents

金属介导的原子和基团转移反应在化学生物学和有机合成中起着重要的作用。这些反应的作用是将含有杂原子的基团（如氮、氧、磷和硫）转移到有机分子中。许多这些过程被认为是通过含有活性金属-杂原子键的配合物进行的。然而，对这些官能团的化学性质及其反应机制的了解远远落后于对涉及金属-碳和金属-氢键的类似转化的了解。因此，基于具有金属-杂原子键的可分离配合物的催化剂和化学计量试剂的开发也处于起步阶段。该项目的总体目标是系统地发展制备含金属杂原子键的过渡金属配合物的一般方法，研究其反应的范围和机制，并将这些反应应用于有机合成中的问题。为即将到来的拨款期提出的研究重点是具有金属-氮（以及-氧和-硫）多重键的试剂，并建立在最近一些这些配合物与有机化合物的高度对映选择性反应的初步发现之上。具体目标是：(1)发展对有机化合物具有反应性的金属-氮多键配合物的一般合成方法；(2)在可能和不可能的情况下，用间接方法对这些分子进行分离和全面鉴定；(3)具有金属-氮多键的手性、对映体溶解配合物的合成；(4)探索这些材料与有机化合物的反应，特别注重寻找在高水平不对称诱导下发生的过程；(5)阐明这些反应的机理，揭示对开发新的催化和化学计量合成试剂有用的一般概念；(6)将这些发展推广到金属-氧和金属-硫多键的类似反应。

Metal-mediated atom- and group-transfer reactions play an important role in chemical biology and organic synthesis. These reactions serve to transfer groups containing heteroatoms such as nitrogen, oxygen phosphorus and sulfur to organic molecules. Many of these processes have been postulated to proceed via complexes that contain reactive metal-heteroatom bonds. However, an understanding of the chemistry of these functionalities and the mechanisms of their reactions lags substantially behind that which is known about analogous transformations involving metal-carbon and metal-hydrogen bonds. As a result, the development of catalysts and stoichiometric reagents based on isolable complexes that bear metal-heteroatom bonds is also in its infancy. The overall goals of this project are the systematic development of general methods for preparing transition metal complexes containing metal-heteroatom bonds, investigation of the scope and mechanisms of their reactions, and application of these reactions to problems in organic synthesis. Research proposed for the upcoming grant period focuses on reagents with metal-nitrogen (as well as -oxygen and -sulfur) multiple bonds, and builds on recent preliminary findings of the highly enantioselective reactions of some of these complexes with organic compounds. The specific goals are: (1) development of general methods for the synthesis of metal complexes with metal-nitrogen multiple bonds that are reactive toward organic compounds; (2) isolation and full characterization of such molecules where it is possible, and where it is not, their characterization by indirect methods; (3) synthesis of chiral, enantioresolved complexes with metal- nitrogen multiple bonds; (4) exploration of the reactions of these materials with organic compounds, with a particular focus on the search for processes that take place with high levels of asymmetric induction; (5) elucidation of the mechanisms of these reactions to uncover general concepts useful for the development of new catalytic and stoichiometric synthetic reagents; (6) extension of these developments to analogous reactions of metal- oxygen and metal-sulfur multiple bonds.