Enantioselective Applications of Designer Synergic Reagents

有机碱金属化合物，特别是有机锂试剂（即含有锂原子和碳原子之间直接键的化合物）是极其重要的合成试剂。事实上，据估计，制药工业生产的所有药物中有98%在其合成过程中的某些环节依赖于这些试剂的使用。一般来说，有机锂化合物是高活性的；然而，这有时与化合物表现出缺乏选择性相结合。为了克服这种情况，通常使用反应性较低但选择性更强的化合物（如有机镁试剂）。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反应。就像人体有左手和右手一样，用于制造新药的某些有机分子（通常称为手性化合物）也可以被认为是左手或右手。在医学上，通常只有一种有机分子的单手形式具有所需的治疗效果；另一种形式通常也会引起严重的副作用。因此，重要的是，合成化学家只能产生一种特定有机化合物的单手形式——在化学中，这被称为对映选择性合成。在本研究中，将首次对上述两个课题进行详细系统的研究，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，将合成许多新的含手性分子的混合金属化合物。各种分析技术将用于全面确定结构-在溶液和固体状态。然后，将对这些化合物如何与有机分子发生反应进行全面而系统的研究。据设想，在不久的将来，这些新的混合金属配合物将用于补充制药工业中众所周知的有机锂试剂。

Organo-alkali metal compounds, especially organolithium reagents (that is compounds that contain a direct bond between a lithium atom and a carbon atom) are extremely important synthetic reagents. Indeed, it has been estimated that 98% of all drugs produced by the pharmaceutical industry rely upon the use of these reagents at some point in their synthesis. In general, organolithium compounds are highly reactive; however, this is sometimes coupled with the compounds exhibiting a lack of selectivity. To overcome this situation, less reactive, but more selective compounds (such as organomagnesium reagents) are often used. 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. Just as the human body has a left and a right hand, certain organic molecules (commonly known as chiral compounds) which are used to make new drugs 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 therapuetic effect; it is also usual that the other handed form induces nasty side effects. It is therefore important that the synthetic chemist can produce only one handed form of a specific organic compound - in chemistry, this is known as enantioselective synthesis.In this research, a detailed systematic investigation of the two aforementioned topics will be combined 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 synthesised. Various analytical techniques will be used to fully determine the structure - both in solution and in the solid state. Then a full and systematic study of how these compounds react with organic molecules will be conducted.It is envisaged that in the near future these new mixed-metal complexes will be used to complement the well known organolithium reagents in the pharmaceutical industry.