Copy of Development of New Catalytic Protocols for Alkene Difunctionalisation

合成方法的基石之一是将容易获得的烯烃转化为具有形式和功能的更复杂的分子。当X-X或X-Y的元素跨双键添加时，则该过程可以被称为“烯烃双官能化”。使用卤素或无机酸可以容易地进行简单的卤化、质子化和羟基化。诸如氧化、还原、二羟基化的反应通常需要更复杂的试剂和/或催化剂，但在合成化学中范围广泛且普遍存在。使用金属催化剂来实现这些目标是非常理想的，这是由于所需的催化剂量少，并且这些关键过程中的许多过程在适当的手性配体存在下是不对称的（例如Sharpless环氧化/二羟基化; Nyori氢化）。另一方面，诸如二胺化、羟基胺化和碳胺化的反应不太常见，并且尽管存在用于实现这一点的直接和间接方法，但它们在数量上很少，底物特异性并且通常给出关于区域选择性的可变结果。这三个长期存在的问题的一般解决方案是非常可取的，并将被合成社区广泛使用。例如，由烯烃不对称合成对映体纯β氨基醇的一般催化方法是“圣杯”反应-特别是对于制药工业，这种结构基序是许多药物的关键在这个提议中，我们希望建立在我们最近的发现上，即在存在再胺化剂的情况下，使用Pd（II）催化剂，二烯可以与脲衍生物选择性地二胺化。氧化剂特别地，我们希望将我们的发现扩展到包括羟基胺化和碳胺化。我们的主要目标是使这些双官能化反应能够在简单的烯烃上进行，而不会出现我们目前观察到的伴随的β-氢化物消除问题。为了实现这一目标，我们的目标是探索使用Pt（II）（PPP）催化剂与迈克加涅教授（北卡罗来纳州，美国）合作。在二烯环化研究中，这些催化剂已被Gagne组显示为异常亲电的，并产生对β-氢化物消除具有极强抗性的C-Pt（II）中间体。我们相信，这些Pt（II）催化剂的应用将开辟烯烃双官能化的新视野。

One of the cornerstones of synthetic methodology is the conversion of readily available alkenes into more complex molecules that have both form and function. When the elements of X-X or X-Y are added across a double bond then this process can be termed 'alkene difunctionalisation'. Simple halogenation, protonation and hydroxylation are easily carried out using halogens or mineral acids. Reactions such oxidation, reduction, dihydroxylation generally require more sophisticated reagents and/or catalysts but are broad in scope and ubiquitous in synthetic chemistry. Use of metal catalysis to achieve these goal is highly desirable due to the small amounts of catalyst required and the fact that many of these key processes are rendered asymmetric in the presence of appropriate chiral ligands (eg Sharpless epoxidation/dihydroxylation; Nyori hydrogenation). On the other hand reactions such as diamination, hydroxyamination and carboamination are much less common and although there exists both direct and indirect methods for achieving this they are few in number, substrate specific and often give variable results with respect to regioselectivity. General solutions to these three longstanding problems are highly desirable and would be used widely by the synthetic community. For example, a general catalytic method for the asymmetric synthesis of enantiopure beta amino alcohols from alkenes is a 'Holy Grail' reaction - especially for the pharmaceutical industry, where this structural motif is key to many drug substances (eg beta-blockers).In this proposal we hope to build on our recent discovery that dienes can be selectively diaminated with urea derivatives using Pd(II) catalysts in the presence of a re-oxidant. In particular we hope to expand our findings to include hydroxyamination and carboamination. Our key goal is to enable the these difunctionalisation reactions to be carried out on simple alkenes without the attendant beta-hydride elimination problems we observe at the moment. To achieve this we aim to explore the use of Pt(II)(PPP) catalysts in collaboration with Prof. Mike Gagne (North Carolina, USA). In diene cyclisation studies these catalysts have been shown by the Gagne group to be exceptionally electrophillic and produce C-Pt(II) intermediates that are extremely resistant to beta-hydride elimination. We believe that application of these Pt(II) catalysts will open up new horizons for alkene difunctionalisation.