Chiral Concepts in s-Block Metal Amide Chemistry

有机锂试剂（即，在锂和碳原子之间含有直接键的化合物）在化学合成中是极其重要的试剂。据估计，95%的药物在其制备过程中的某个时候依赖于这些基础试剂的使用。一般来说，有机锂化合物是非常活泼的;然而，这有时与即使在非常低的低温下进行反应时也表现出缺乏选择性的化合物相结合。这对合成化学家来说是一个巨大的障碍！为了克服这种情况，需要反应性较低但选择性较高的化合物[例如有机镁（例如，Grignard）或有机锌（例如，Reformatsky）试剂];然而，这些试剂通常太惰性。最近的研究表明，通过将锂试剂与镁（或锌）试剂结合，可以产生一种全新的，在许多情况下令人惊讶的化学物质。令人着迷的是，在这些情况下，反应性不能单独使用单核苷酸化合物来复制！这项工作的另一个重要主题是有机分子的产生（即，不含金属原子的分子），其可用作关键药物的构建单元。就像人类有左手和右手一样，某些有机分子（称为手性化合物）也可以被认为是左手或右手。在医学中，通常只有一种手性形式的有机分子具有所需的治疗效果;另一种手性形式也通常会引起讨厌的副作用。因此，关键是合成化学家可以很容易地产生一个特定的有机化合物的单手形式。本研究将系统地研究上述两个课题，并首次将其联合收割机结合起来，即利用碱金属-镁或碱金属-锌配合物进行对映选择性合成。在本研究的第一部分中，将制备许多新的含有手性分子的混合金属化合物。将使用各种分析技术来确定它们在溶液和固态中的结构。我们将对这些化合物与有机分子的反应进行系统的研究，并设想在不久的将来，这些新的“双金属”将被用来补充目前在制药工业中占据市场的众所周知的有机锂试剂。另一个将被探索的领域是碱金属氨化物的化学。尽管它们的广泛使用，碱金属酰胺及其配合物的结构化学继续春天许多迷人的惊喜。我们最近观察到，各种大小的分子环-仅由碱金属阳离子和酰胺阴离子组成-可以在手性二胺配体存在下捕获阴离子（如氢氧根和氯离子）。这一新的大环化合物研究方向彻底改变了传统的冠醚化学，为简单的碱金属酰胺/二胺化合物在阴离子识别化学中的应用打开了大门。这一新的协同化学研究方向的成果无疑将吸引广泛的学者，包括无机、有机金属和有机化学家，以及超分子化学家，由于该领域的强结构和配位化学性质。这种对映选择性合成的新方法也将引起化学工业（精细化学品、制药、农用化学品等）研究人员的极大兴趣。他们致力于制造手性分子（新的和旧的！）以轻松的方式。

Organolithium reagents (i.e., compounds that contain a direct bond between a lithium and a carbon atom) are extremely important reagents in chemical synthesis. It has been estimated that 95% of all pharmaceuticals rely upon the use of these cornerstone reagents at some point in their preparation. In general, organolithium compounds are very reactive; however, this is sometimes coupled with the compounds exhibiting a lack of selectivity even when the reactions are carried out at very low, cryogenic temperatures. This is a massive hurdle to the synthetic chemist! To overcome this situation, less reactive, but more selective compounds [such as organomagnesium (e.g., Grignard) or organozinc (e.g., Reformatsky) reagents] are often used; however, these reagents are often too inert. Recent research has shown that by combining a lithium reagent with a magnesium (or zinc) one, a whole new and in many cases surprising chemistry can be produced. Fascinatingly, in these cases the reactivity cannot be replicated using the monometallic compounds on their own! Another important theme of this work is the generation of organic molecules (i.e., molecules which contain no metal atoms) which can be used as building blocks for key pharmaceuticals. Just as human beings have a left and a right hand, certain organic molecules (known as chiral compounds) can also be considered left- or right-handed. In medicine, it is common that only one handed form of an organic molecule has the required therapeutic effect; it is also usual for the other handed form to induce nasty side effects. Therefore it is critical that the synthetic chemist can easily produce only one handed form of a specific organic compound. In chemistry this is known as enantioselective synthesis.This research will systematically investigate the two aforementioned topics and combine them for the first time - that is enantioselective synthesis using alkali metal-magnesium or alkali metal-zinc complexes. During the first part of this research many new mixed-metal compounds which contain chiral molecules will be prepared. Various analytical techniques will be used to determine their structure, both in solution and in the solid state. Then a systematic study of how these compounds react with organic molecules will be conducted.It is envisaged that in the near future these new "bimetallics" will be used to complement the well known organolithium reagents that presently corner the market in the pharmaceutical industry. Another area which will be explored is the chemistry of alkali metal amides. Despite their widespread usage, the structural chemistry of alkali metal amides and their complexes continues to spring many fascinating surprises. We have recently observed that molecular rings of various sizes - consisting only of alkali metal cations and amide anions - can capture anions (such as hydroxide and chloride) in the presence of chiral diamine ligands. This new direction in s-block macrocyclic chemistry turns conventional crown ether chemistry on its head and opens the door for simple alkali metal amide/diamine compositions to be utilised in anion recognition chemistry.Results from this new direction within synergic chemistry will undoubtedly appeal to a broad spectrum of academics, including inorganic, organometallic and organic chemists, as well as to supramolecular chemists due to the strong structural and coordination chemistry nature of the area. This new methodology in enantioselective synthesis will also be of considerable interest to researchers in the chemical industry (fine chemicals, pharmaceutical, agrochemical etc.) who strive to produce chiral molecules (new and old!) in a facile manner.