Multivicinal fluorinated cyclohexanes, a new structural motif in organic chemistry

本研究计划旨在介绍六氟环己烷(HFCH)及其衍生物作为有机化学中的一个新的主题。与邻位六氟代环己烷有关的文献非常稀少。它们几乎没有被研究过。然而，有迹象表明，这个基序可以赋予人们诱人和重要的性质，如果能够建立合成路线，这将在有机化学中开辟一个新的高度影响的领域。我们最近的合成重点是制备非环多取代氟化合物，为本项目的合成和分析奠定了良好的基础。从本质上讲，我们现在想要合成全合成的1，2，3，4，5，6-六氟环己烷(ALL-SYN)作为这项研究计划的旗舰分子，但除此之外，我们还想探索围绕这个分子的化学，并获得非对映异构体和衍生物以实现功能化和实用性。理论研究表明，全合成的HFCH是一个高极性的分子。它以前从未被提出过，而且在整个文献中只有三次提到这种化合物。2004年的一项理论研究，日本的一项专利(没有分离出结构)，以及1969年化学家的一份耐人寻味的报告。这些化学家使用元素氟(F2)和CoF3/KH来氟化苯，并分离出一种固体组分，他们从核磁共振和质谱学数据中得出结论，即HFCH的全反式异构体。他们还得出结论，这种异构体在化学上是稳定的，尽管他们拥有的特定异构体是猜测的。这是报道的唯一一种合成方法。2004年的理论研究预测了高极性分子，特别是全合成HFCH。它的预测偶极矩约为8.03 Debey。为了准备这一提议，我们还进行了理论研究，并评价了全合成HFCH的静电表面图，该图显示了分子的+ve面和a-ve面。计算还预测，这些分子将堆叠在一起，一个叠加在另一个之上。如果是这样的话，这种化合物及其立体异构体将具有有趣的固态和液晶行为。在此背景下，本研究将对HFCH异构体的控制合成进行研究，并对其性质(X-射线、核磁共振、差示扫描量热等)进行评价。我们感觉能够制造这些分子，因为我们最近发现了立体选择性地合成多达五到六个氟的无环邻位氟基序的方法。该化学利用了环氧化物与HF试剂的开环反应，然后生成的氟化氢的氟化反应。因此，通过将我们的方法和专业知识应用于环己烷三环氧化物，就有一条明显的路线可以获得HFCH。所需三环氧化物前体的不同非对映异构体在文献中描述得很好，所以我们应该能够取得良好的进展。我们还将探索1，2，3，4，5-五氟环己烷-6-醇醚和酯类化合物的制备方法，以便将该模体整合到更大的分子结构中。候选液晶分子和长链硫醇也被确定为合成目标，这些分子将通过形成自组装单分子膜进行评估。我们还确定了用于聚合反应的四氟环己二醇单体，作为将这一新基序纳入聚合物材料的一种手段。如果我们能够开发这一新主题的路线，描述它们的一般行为，并开发合成垂直效应，使其能够在不同的领域应用和展示，该计划将是成功的。要求资助一名训练有素的博士后研究员三年，并支付适当的消耗品费用，以开发该项目并探索概述的应用。

This research programme aims to introduce hexafluorocyclohexanes (HFCH) and their derivatives as a novel motif in organic chemistry. There is a very sparce literature associated with vicinal hexafluorinated cyclohexanes. They have hardly been studied. However there are indications that this motif could impart attractive and important properties and if synthesis routes could be established this would open up a new and high impact area in organic chemistry. Our recent synthesis focus on the preparation of acyclic multivicinal fluorinated compounds lays a good synthesis and analysis foundation for this programme. In essence we want now to synthesise the all-syn 1,2,3,4,5,6-hexafluorocyclohexane (all-synHFCH) as the flagship molecule of this research proposal, but alongside this, to explore chemistry around this molecule and access diastereoisomers and derivatives for functionalisation and utility.Theory studies indicate that all-synHFCH is a highly polar molecule. It has never been made before and there are only three references in the entire literature discussing this compound. A theory study in 2004, a Japanese patent (no structures isolated) and a an intriguing report from chemists in 1969. These chemist were fluorinating benzene using elemental fluorine (F2) and CoF3/KH and they isolated a solid fraction which they concluded from NMR and mass spec data was the all-trans isomer of HFCH. They also concluded that this isomer was chemically stable, although the particular isomer they had was conjecture. This is the only synthesis reported. The theory study in 2004 predicted highly polar molecules, especially for all-synHFCH. It had a predicted dipole moment of about 8.03 Debey. We also carried out a theory studies in preparation for this proposal and have evaluated an electrostatic surface map of all-syn HFCH which shows a +ve face and a -ve face to the molecule. Calculations also predict that that the molecules will stack, one on top of the other. If this is the case this compound and its steroisomers will have interesting solid state and liquid crystalline behaviour. So this becomes a particualry attractive structural motif, yet been explored by chemists.With this background the research programme will investigate the controlled synthesis of HFCH isomers and evaluate their properties (X-ray, NMR, DSC etc). We feel able to make these molecules because we have recently discovered methods for the stereoselective synthesis of acyclic vicinal fluorine motifs of upto five and six fluorines. That chemistry utilised epoxide ring opening reactions with HF reagents, and then fluorination reactions of the resultant fluorohydrins. So by applying our methods and expertise to cyclohexanetriepoxides, then there is an obvious route to HFCH's. Different diastereoisomers of the required triepoxides precursors are very well described in the literature, so we should be able to make good progress. We will also explore the preparation of ether and ester derivatives of 1,2,3,4,5-pentafluorocyclohexan-6-ols, such that this motif can be incorporated into larger molecular architectures. Candidate liquid crystal molecules and also long chain thiols which will be assessed by forming self assembling monolayers, have been identified as synthetic targets. We also identify tetrafluorocyclohexandiol monomers for polymerisation reactions, as a means of incorporating this novel motif into polymeris materials. The programme will be a success if we can develop routes to this new motif, characterise their general behaviour, and develop synthetic versitility such that it can be applied and demonstrated in a diversity of arenas.Funding for a trained postdoctoral researcher for three years, with appropriate consumables costs, is requested to develop this project and explore the outlined applications.