Small molecule functionalization by metal-mediated borylene transfer chemistry

饱和和不饱和有机分子与含硼试剂的反应代表了将官能团引入有机底物的一系列非常强大和通用的方法，这些方法已被广泛利用，例如在药物、天然产品和功能材料的合成中。所得的硼衍生物产物可直接用于进一步合成(如铃木-宫浦C-C偶联反应中的芳基硼酸酯)，或转化为一系列更有用的官能团(如醇、胺等)。使用既定的协议。使用硼烷试剂为有机底物引入官能团的里程碑式的反应包括：(I)多键的氢化和二硼化反应；(Ii)钯催化的芳基卤化物转化为芳基硼酸盐；以及(Iii)Rh或Ir络合物催化的烷烃和芳烃的直接C-H键官能化。对于这些方法中的每一种，都可以在过渡金属的配位范围内实现对B-C成键步骤的控制，在某些情况下，通过使用手性配体集来实现对映体/非对映选择性合成的可能性。过渡金属硼基配合物LNM-BX2广泛参与BX2片段向有机底物的传递(例如，在氢化/二硼化和C-H活化过程中)，因此一直是最近密集研究的主题。相比之下，硼烯片段(：BX)的化学还没有在很大程度上被利用来形成C-B键，尽管与卡宾(：Cr2)和硅烯(：Sir2)片段有明显的相似之处，而且这些亚价基14系统涉及到广泛的有用的反应活性。因此，例如，卡宾在歧化、环丙烷化和插入化学中的应用，以及硅烯在C-C键形成中的应用，都得到了广泛的研究。在一定程度上，缺乏类似的硼化学反映了“游离”硼烯的极不稳定性质及其不分青红皂白的反应活性，例如，对C-H/C-C键的反应。在卡宾和硅烯的情况下，已经成功地采用了一种策略来调节反应性，即将反应片段限制在过渡金属的配位球上。我们打算利用这种方法来开发基于含有亚乙撑片段的金属络合物的受控成键化学。在一定程度上，这将建立在Aldridge小组之前的工作基础上，该小组已经开辟了合成类似于Fischer卡宾/亚乙基烯的亚丁基络合物的路线，并揭示了它们的基础化学方面。重要的是，这些研究已经确定了含有氨基丁烯片段的阳离子配合物达到了平衡，既足够坚固，易于合成/处理，又表现出对原型有机和无机键的清洁室温反应能力。我们打算在这一初步工作的基础上，开发将含硼片段引入有机分子的新方法，主要集中(在第一个实例中)开发插入和环加成协议，这些协议使用现有的硼化方法是不可能的(或很难实现的)。首先，我们将通过研究金属硼烯络合物中化学计量比的过程来探索机理和选择性问题，最终目的是将这些基本步骤纳入催化过程。第二个目标将需要并行发展，特别是开发利用容易获得的硼烷前体的直接合成方法。因此，这两个目标：并行开发合成方法和开发反应模式将构成拟议工作的基础。

Reactions of saturated and unsaturated organic molecules with boron-containing reagents represent a very powerful and versatile range of methodologies for the introduction of functionality into organic substrates, which have been widely exploited, e.g. in the syntheses of pharmaceuticals, natural products and functional materials. The resulting boron-derivatized products can be exploited directly for further synthesis (e.g. aryl boronate esters in Suzuki-Miyaura C-C coupling), or converted to a range of more useful functional groups (e.g. alcohols, amines, etc.) using established protocols. Landmark reactions in which borane reagents have been used to introduce functionality into organic substrates include (i) hydro- and diboration of multiple bonds; (ii) palladium-catalysed conversion of aryl halides to aryl boronates; and (iii) direct C-H bond functionalization of alkanes and arenes catalysed by rhodium or iridium complexes. For each of these methodologies, control of the B-C bond-forming step can be achieved within the coordination sphere of a transition metal, in some cases opening up the possibility for enantio-/diastereoselective syntheses via the use of chiral ligand sets. Transition metal boryl complexes, LnM-BX2, are widely implicated in the delivery of the BX2 fragment to organic substrates (e.g. in both hydro-/diboration and C-H activation processes) and as such have been the subject of intense recent investigation.By contrast, the chemistry of the borylene fragment (:BX) has not been exploited to any great extent in the formation of C-B bonds, despite obvious parallels with carbene (:CR2) and silylene (:SiR2) fragments, and the wide range of useful reactivity in which these subvalent group 14 systems have been implicated. Thus, for example, the applications of carbenes in metathesis, cyclopropanation and insertion chemistries, and of silylenes in C-C bond formation, have been widely investigated. In part, the lack of analogous boron chemistry reflects the extremely labile nature of 'free' borylene and its indiscriminate reactivity, e.g. towards C-H/C-C bonds. A strategy which has been successfully adopted to modulate reactivity in the cases of carbenes and silylenes is to confine the reactive fragment to the coordination sphere of a transition metal. We intend to exploit this approach to develop controlled bond-forming chemistry based on metal complexes containing the borylene fragment. In part, this will build on previous work within the Aldridge group which has opened up synthetic routes to borylene complexes analogous to Fischer carbenes/vinylidenes, and uncovered aspects of their fundamental chemistry. Crucially, these studies have identified cationic complexes containing the aminoborylene fragment as achieving the balance between being sufficiently robust for ease of synthesis/handling, but displaying clean room temperature reactivity towards archetypal organic and inorganic bonds.We intend to build on this preliminary work to develop new methodologies for introducing boron-containing fragments in to organic molecules, primarily concentrating (in the first instance) on developing insertion and cycloaddition protocols which are not possible (or are very difficult to achieve) using existing borylation methodologies. Initially we will explore issues of mechanism and selectivity by examining processes which are stoichiometric in the metal borylene complex, with the ultimate aim of incorporating these fundamental steps into catalytic processes. This second goal will require parallel developments leading, in particular, to the development of direct synthetic approaches utilizing readily-available borane precursors. Thus, these two goals: side-by-side development of synthetic methodology and exploitation of reactivity patterns will form the basis for the proposed work.