Complexity-Generating Hydration Reactions via Metal-Catalysed Reaction of Boronic Acids with Alkenes

含有碳-碳双键的简单有机分子，称为烯烃，是广泛存在的大宗化学品，用作合成一系列更复杂的具有有用性质的分子的基本原料--医药、精细化学品、农用化学品、聚合物等。在这项建议中，我们概述了将烯烃直接转化为复杂分子结构的新催化策略。在每种情况下，通过在烯烃的碳-碳双键上正式加成水分子来启动一系列新的反应(水合反应)。水与烯烃的反应可能很难完成，因为许多烯烃不溶于水。它通常是使用强酸(如硫酸)或汞盐(毒性很大)实现的。在这项研究中，我们将在我们实验室以前工作的基础上采用一种新的策略，即水分子与有机含硼化合物相连，使其能够在有机溶剂中‘溶解’，并在合适的催化剂存在下更容易发生反应(在本项目中，将使用更高效、毒性更低的基于钯、铂和金等金属的催化剂--我们的初步实验证明这种催化剂是有效的)。这一策略可能非常有效，因为硼原子可以用于进一步的(水合后)化学反应，以构建复杂的产品。这些新的反应策略将用于合成广泛的产品，包括医学研究中针对疾病靶点进行筛选的感兴趣分子。这将使我们能够与适当的生物学家建立合作，以便将我们的新发现应用于开发新的医疗方法。

Simple organic molecules containing carbon-carbon double bonds, known as alkenes, are widely available bulk chemicals that serve as basic starting materials for the synthesis of a wide range of more complex molecules with useful properties - pharmaceuticals, fine chemicals, agrochemicals, polymers, etc. In this proposal we outline new catalytic strategies for the direct conversion of alkenes into complex molecular structures. In each case, a novel sequence of reactions is initiated via the formal addition of a molecule of water across the carbon-carbon double bond of the alkene (a hydration reaction). The reaction of water with an alkene can be difficult to accomplish as many alkenes do not dissolve in water. It is usually achieved using either strong acids (e.g. sulfuric acid) or mercury salts (which are very toxic). In this research we will employ a new strategy based upon previous work from our laboratory in which the water molecule is attached to an organic boron-containing compound, enabling it to be 'dissolved' in an organic solvent and to react more readily in the presence of a suitable catalyst (In this project more efficient and considerably less toxic catalysts based around metals such as palladium, platinum and gold will be used - our preliminary experiments have demonstrated that such catalysts are effective). This strategy is potentially very powerful as the boron atom can be used in further (post-hydration) chemical reactions to construct complex products. These new reaction strategies will be of use for the synthesis of a wide range of products including molecules of interest for screening against disease targets in medical research. This will enable us to build up collaborations with appropriate biologists in order to apply our new discoveries in the development of new medical treatments.