A metathesis approach to volatile olefins: synthesis of 18O-allyl alcohol.
A metathesis approach to volatile olefins: synthesis of 18O-allyl alcohol.
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挥发性烯烃的复分解方法：18O-烯丙醇的合成。
DOI：
10.1002/chem.201100271
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Lloyd-Jones GC
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文献类型：
--
作者：
Lloyd-Jones GC
同位素标记是阐明反应机制、生物合成途径和代谢通量的关键工具由于成本的原因，大多数标记化合物都是由尽可能简单的同位素富集前体制备的，理想情况下只需几步。对于更奇特的同位素，这种合成必然是在小范围内进行的。在这种情况下，虽然化学本身可能很简单，但如果中间产物或最终产物是挥发性的，那么合成和分离可能是一项非常具有挑战性的工作。我们最近在试图制备烷基-[18O]-烯丙基酯进行机理研究时，正好遇到了这些问题这一经验促使我们设计了一种制备挥发性同位素标记烯烃的通用方法，在非常温和的条件下，直接分离所需的化合物，相对不含水、有机溶剂和共合成污染物。我们的策略是将所需烯烃的前驱体对（X， Y，方案1）连接到分子量更高的连接体上，使合成操作更容易进行，[3]和最终无溶剂的[4]催化闭环复分解[5]（RCM）过程中，结合烯烃末端，释放[6]并缩合所需的烯烃。本文报道了[18O]-烯丙醇（[18O]-1）的合成，具有良好的化学纯度和同位素纯度，并概述了该方法的更广泛的潜在用途。烯丙醇(1)在任何比例下都是完全溶于水的，沸点为96-988C，并且易于与几乎所有常见的实验室溶剂形成共沸物。因此，在没有专门仪器的情况下，在小规模（< 250 μL）的纯状态下分离烯丙醇是具有挑战性的，这是RCM方法（方案1）有效性的一个范例。已经报道了许多制备[18O]-1的方法。[7,8]许多这些过程产生[18O]-1的溶液，而不是纯物质，连同合成的副产物，然后不经纯化就用于进一步的化学或光谱学迄今为止报道的最可行的方法是Shine和Kupczyk-Subotkowska的方法，该方法采用五步序列法获得了38%的纯度[18O]-1，其中同位素掺入率为50%所有报告的程序都有缺点；例如，有些涉及在密封容器中长时间加热，或使用高氯酸盐，或给予低同位素合并，或不易适应多种标记模式，或在我们手中产生大量的二烯丙基醚作为副产物。
Isotopic labelling is a key tool in the elucidation of reaction mechanisms, biosynthetic pathways and metabolic flux.[1] For reasons of cost, most labelled compounds are prepared from as simple an isotopically enriched precursor as possible, and ideally in just a few steps. With the more exotic isotopes, such syntheses are by necessity conducted on a small scale. In such circumstances, although the chemistry itself may be straightforward, if an intermediate or final product is volatile then the synthesis and isolation can be a very challenging undertaking. We recently encountered exactly these issues when attempting to prepare alkyl-[18O]-allyl esters for a mechanistic investigation.[2] The experience prompted us to design a general approach for the preparation of volatile isotopically labelled olefins, under very mild conditions and with direct isolation of the desired compound relatively free of water, organic solvent and co-synthetic contaminants. Our strategy was to attach a precursor pair (X, Y, Scheme 1) for the desired olefin to a linker of much higher molecular weight, allowing synthetic manipulations to be conducted without difficulty,[3] and in a final solvent-free [4] catalytic ring-closing metathesis [5](RCM) process, unite the alkene termini, to release [6] and condense the desired olefin. Herein we report on the synthesis of [18O]-allyl alcohol ([18O]-1), in good chemical and isotopic purity, and outline the broader potential utility of the method. Allyl alcohol (1) is completely water soluble in all proportions, has a boiling point of 96–988C, and is prone to formation of azeotropes with almost all common laboratory solvents. As a consequence, without the benefit of specialised apparatus, isolation of allyl alcohol in a pure state is challenging on a small scale (< 250 μL) and an exemplar for the efficacy of the RCM approach (Scheme 1). A number of methods for the preparation of [18O]-1 have been reported.[7, 8] Many of these procedures generate a solution of [18O]-1, rather than pure material, together with the synthetic side products, which is then used without purification in further chemistry or spectroscopy.[7] The most amenable route reported to date is from Shine and Kupczyk-Subotkowska, in which a five-step sequence afforded pure [18O]-1 in 38% yield with 50% isotopic incorporation.[8] All of the reported procedures have shortcomings; for example, some involve prolonged heating in sealed vessels, or the use of perchlorate salts, or give low isotopic incorporations, or are not readily adapted to multiple labelling patterns, or, in our hands, generated substantial quantities of diallyl ether as a side product.
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DOI：
--
发表时间：
1986
期刊：
影响因子：
--
作者：
Hyung;Jiann;R. L. Kuczkowski
通讯作者：
R. L. Kuczkowski
使用同位素研究反应机制
DOI：
--
发表时间：
1997
期刊：
影响因子：
--
作者：
U. Maitra;J. Chandrasekhar
通讯作者：
J. Chandrasekhar
去质子化烯丙基苯基乙酸酯在气相中的Sigmatropic重排
DOI：
--
发表时间：
1987
期刊：
影响因子：
--
作者：
P. Eichinger;J. Bowie;R. Hayes
通讯作者：
R. Hayes
影响因子：
15
作者：
Evans, Louise A.;Fey, Natalie;Purdie, Mark
通讯作者：
Purdie, Mark
影响因子：
5.2
作者：
Chung, Cheol K.;Grubbs, Robert H.
通讯作者：
Grubbs, Robert H.