Copy of Development of New Catalytic Protocols for Alkene Difunctionalisation

合成方法学的基石之一是将容易获得的烯烃转化为既有形式又有功能的更复杂的分子。当X-X或X-Y的元素跨双键加成时，这个过程可以被称为‘烯烃去功能化’。使用卤素或无机酸可以很容易地进行简单的卤化、质子化和羟化。氧化、还原、二羟基化等反应通常需要更复杂的试剂和/或催化剂，但范围很广，在合成化学中无处不在。使用金属催化来实现这些目标是非常可取的，因为所需的催化剂数量很少，而且在适当的手性配体的存在下，这些关键过程中的许多过程是不对称的(例如夏普莱斯环氧化/二羟基化；Nyori氢化)。另一方面，二羟胺化、羟胺化和碳胺化等反应很少见，虽然有直接和间接的方法来实现这一点，但它们的数量很少，底物特定，并且经常根据区域选择性得出不同的结果。对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，从烯烃不对称合成对映体β氨基醇的一种通用催化方法是圣杯反应--特别是对于制药行业，这种结构基序是许多药物(如β-阻滞剂)的关键。在这个建议中，我们希望建立在我们最近的发现基础上，即在复氧化剂存在的情况下，使用Pd(II)催化剂可以选择性地将双烯与尿素衍生物缩合。特别是，我们希望将我们的发现扩大到包括羟胺化和碳胺化。我们的主要目标是使这些去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随之而来的β-氢化物消除问题。为了实现这一目标，我们的目标是与Mike Gagne教授(美国北卡罗来纳州)合作探索铂(II)(PPP)催化剂的使用。在二烯环化研究中，Gagne小组已经证明这些催化剂具有特殊的亲电性，并产生极耐β-氢化物消除的C-铂(II)中间体。我们相信，这些铂(II)催化剂的应用将为烯烃双官能化开辟新的前景。

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.