Asymmetric Assembly of Cobalt Metallocenes - Accessible Building Blocks for Novel Catalysts

以“手”形式存在的分子在许多研究领域变得越来越重要，尤其是在医药行业，这类化合物的年销售额现在超过1000亿美元。“手性”分子以两种不可重叠的镜像形式存在，其中只有一种通常表现出所需的特性，例如介导生物活性的能力。生成此类分子的最有效和最经济的方法之一是使用少量金属/配体催化剂，选择性地生成一种“递交”形式而不是另一种形式。该策略的核心是配体，它包含成功控制金属上发生的反应所需的信息，它附着在金属上。因此，许多不同的配体类型已经被合成和测试，但令人惊讶的是，某些群体，或被创造的特权结构，是如何成功地广泛应用的。其中一种是茂金属，通常是铁基化合物二茂铁的衍生物。本文提出了一种合成钴基茂金属的新策略，该策略比现有的二茂铁方法简单得多。此外，它具有更大的可变性和灵活性，可以快速获取和优化给定金属催化“手性”合成的配体。

Molecules that exist in 'handed' form are of growing importance to many research areas, not least the pharmaceutical industry where sales of such compounds now exceed $100 billion per annum. 'Handed' molecules exist in two non-superimposable mirror image forms of which only one usually displays the desired property such as an ability to mediate biological activity. One of the most efficient and cost effective means to generate such molecules is to employ a small quantity of a metal/ligand catalyst that selectively generates one 'handed' form over the alternative. Central to this strategy is the ligand which contains the information required to successfully control the reaction taking place at the metal, to which it is attached. Thus many different ligand types have been synthesised and tested, yet it is striking how certain groups, or privileged structures as they have been coined, are successful for a wide range of applications. One of these groups is the metallocenes, normally derivatives of iron-based compounds called ferrocenes. In this proposal a new strategy is outlined for the synthesis of cobalt based metallocenes that is significantly simpler than the existing ferrocene methodology. Furthermore, it has much greater variability and flexibility that will enable rapid access to, and optimisation of, a ligand for a given metal catalysed 'handed' synthesis.