Powerful insight into catalytic mechanisms through simultaneous monitoring of reactants, products, and intermediates.
Powerful insight into catalytic mechanisms through simultaneous monitoring of reactants, products, and intermediates.
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DOI：
10.1002/anie.201102630
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发表时间：
2011-08
影响因子：
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通讯作者：
Krista L Vikse;Z. Ahmadi;C. Manning;D. Harrington;J. McIndoe
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文献类型：
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作者：
Krista L Vikse;Z. Ahmadi;C. Manning;D. Harrington;J. McIndoe
电喷雾离子化质谱（ESIMS）已成为研究有机金属催化反应机理的重要工具。分析速度快，可以检测到低浓度的中间体，复杂的混合物易于处理。钯催化的C-C键形成反应是ESIMS研究最多的反应。虽然大多数这些调查都集中在短寿命或低浓度的中间体的结构鉴定，最近的一些研究监测的强度的中间体或反应物和产品随着时间的推移。14]然而，还没有人证明这种技术能够在标准反应条件下同时提供反应物、产物、副产物和低丰度中间体的强大动力学信息。我们在此展示了这些信息在主导反应设计中的作用。无铜Sonogashira（Heck炔基化）反应广泛应用于天然产物、药物和新材料的合成，但其机理尚不清楚。理想情况下，应在典型反应条件下观察反应，以获得关于机理的有意义的信息，因为在这种条件下，阴离子和碱18]以及炔被认为充当钯的配体，对反应效率具有复杂的影响。在大多数情况下，需要大量过量的胺碱来促进反应;然而，碱的确切作用是有问题的。Dieck、Heck和Amatore等人提出了一种碳钯化机制，其中末端炔进行碳钯化，碱消耗在形成产物的b-氢化物消除过程中形成的H。Ljundahl等人优选脱质子化机理，其中根据炔的电子性质，胺对末端炔的脱质子化发生在阳离子中间体[Pd（Ar）（PR 3）（NR "3）（HC CR"）]或中性中间体[Pd（Ar）（PR 3）（X）（HC CR "）]。还提出了以[Pd（PR_3）_2X]和[Pd（PR_3）（X）（Ar）（CCR ″）]中间体为特征的阴离子机理。含钯中间体的身份已提出的电化学或NMR光谱数据的基础上，但不是通过直接观察。带电标签是检测ESIMS不可见的物质所必需的，24]这一想法首先由Adlhart和Chen引入;我们使用了用六氟磷酸盐[p-IC6H4CH2PPh3][PF6]官能化的芳基碘。这种标签由于其高表面活性而提供非常低的检测限，并且非配位的抗衡离子减少了离子配对。带电基团的庞大性质确保电离效率对离子的剩余结构基本上不敏感，因此各种离子的强度非常接近于它们的真实的浓度（参见支持信息）。通过使用加压样品注入（PSI）在典型反应条件下收集的关于反应进程的ESIMS数据与1H NMR和UV/维斯光谱数据（图1）很好地比较。数据点的数量要高得多，
Electrospray ionization mass spectrometry (ESIMS) has become a valuable tool in the mechanistic study of organometallic catalytic reactions. Analysis is fast, intermediates at low concentrations can be detected, and complex mixtures are tractable. The family of palladium-catalyzed C C bondforming reactions are the most studied by ESIMS. Although the majority of these investigations have focused on the structural identification of short-lived or low-concentration intermediates, some recent studies have monitored the intensities of intermediates or reactants and products over time. 14] However, no one has yet shown this technique to be capable of providing robust kinetic information for reactants, products, by-products, and low-abundance intermediates simultaneously and under standard reaction conditions. We show herein how powerful this information can be in leading reaction design. The copper-free Sonogashira (Heck alkynylation) reaction is widely used in the synthesis of natural products, pharmaceuticals, and novel materials, but the mechanism is not well understood. Ideally, the reaction should be observed under typical reaction conditions for meaningful information to be obtained about the mechanism, because under such conditions anions and bases 18] as well as alkynes are thought to act as ligands for palladium, with complex effects on the reaction efficiency. In most cases, a large excess of an amine base is required to promote reaction; however, the exact role of the base is in question. Dieck and Heck and Amatore et al. suggested a carbopalladation mechanism in which the terminal alkyne undergoes carbopalladation and the base consumes the H formed during the b-hydride elimination that forms the product. Ljundahl et al. prefer a deprotonation mechanism in which deprotonation of the terminal alkyne by the amine occurs from the cationic intermediate [Pd(Ar)(PR3)(NR’3)(HC CR’’)] or the neutral intermediate [Pd(Ar)(PR3)(X)(HC CR’’)], depending on the electronic nature of the alkyne. An anionic mechanism has also been proposed in which [Pd(PR3)2X] and [Pd(PR3)(X)(Ar)(CCR’’)] intermediates feature. The identity of palladium-containing intermediates has been proposed on the basis of electrochemical or NMR spectroscopic data but not through direct observation. Charged tags are required for the detection of species otherwise invisible to ESIMS, 24] an idea first introduced by Adlhart and Chen; we used an aryl iodide functionalized with a phosphonium hexafluorophosphate salt, [p-IC6H4CH2PPh3] [PF6] . This tag provides very low detection limits owing to its high surface activity, and the noncoordinating counterion reduces ion pairing. The bulky nature of the charged group ensures that the ionization efficiency is largely insensitive to the remaining structure of the ion, so the intensity of the various ions correspond very closely to their real concentration (see the Supporting Information). ESIMS data on reaction progress collected under typical reaction conditions by using pressurized sample infusion (PSI) compare well with H NMR and UV/Vis spectroscopic data (Figure 1). The number of data points is much higher for