在有機(jī)合成中常見(jiàn)的鈀催化偶聯(lián)反應(yīng)有：Suzuki-Miyaura偶聯(lián), Stille偶聯(lián), Negishi偶聯(lián), Kumada偶聯(lián), Hiyama偶聯(lián), Sonogashira偶聯(lián), Heck反應(yīng), Buchwald-Hartwig反應(yīng)等等。因此常見(jiàn)的鈀催化劑應(yīng)用非常廣泛，雖然這些催化劑都已商業(yè)化，但對(duì)于大規(guī)模生產(chǎn)的反應(yīng)，可以自己制備降低成本。

Pd(PPh3)4的制備

A mixture of palladium dichloride (17.72 g., 0.10 mole), triphenylphosphine (131 g, 0.50 mole), and 1200 ml of dimethyl sulfoxide is placed in a single-necked, 2L, round-bottomed flask equipped with a magnetic stirring bar and a dual-outlet adapter. A rubber septum and a vacuum-nitrogen system are connected to the outlets, The system is then placed under nitrogen with provision made for pressure relief through a mercury bubbler. The yellow mixture is heated by means of an oil bath with stirring until complete solution occurs (ca. 140 ℃). The bath is then taken away, and the solution is rapidly stirred for approximately 15minutes. Hydrazine hydrate (20 g, 0.40 mole) is then rapidly added over approximately 1 minute from a hypodermic syringe. A vigorous reaction takes place with evolution of nitrogen. The dark solution is then immediately cooled with a water bath; crystallization begins to occur at ca. 125℃. At this point the mixture is allowed to cool without external cooling. After the mixture has reached room temperature it is filtered under nitrogen on a coarse, sintered-glass funnel. The solid is washed successively with two 50 ml. portions of ethanol and two 50 ml portions of ether. The product is dried by passing a slow stream of nitrogen through the funnel overnight. The resulting yellow crystalline product weighs 103.5-108.5 g. (90-94% yield).A melting point determination on a sample in a sealed capillary tube under nitrogen gave a decomposition point of 116℃ (uncorrected). This compares with a similar determination(115℃) performed on the product prepared by the method of Malatesta and Angoletta.

Properties:

The Pd(PPh3)4 complex obtained by this procedure is a yellow, crystalline material possessing moderate solubilities in benzene (50 g/L), methylene chloride, and chloroform.The compound is less soluble in acetone, tetrahydrofuran and acetonitrile. Saturated hydrocarbon solvents give no evidence of solution. Although the complex may be handled in air, it is best stored under nitrogen to ensure its purity.

Pd(PPh3)2Cl2的制備

將PdCl2 (50 g, 0.284 mol)和PPh3 (162.5 g, 0.62 mol) 加入苯腈（150 mL）中，氮?dú)庵脫Q三次，升溫到200℃，反應(yīng)30 分鐘，降溫至室溫析出晶體，濾出固體，用乙醚洗滌，抽干，得到產(chǎn)品（362 g, 95.8 %）。

Pd(dppf)Cl2的制備

To absolute acetonitrile (1950 mL) degassed via three vacuum/nitrogen ingress cycle was added dichloropalladium (13 g, 73 mmol), the mixture was refluxed at 90~100 °C overnight. The reactant was concentrated to obtain Pd(CH3CN)2Cl2 as orange solid. To a suspension of Pd(CH3CN)2Cl2 (19 g, 73 mmol) in benzene (680 mL) was added a solution of dppf (40.6 g,73 mmol) in benzene (680 mL), the mixture was stirred at rt overnight, the reddish brown precipitate formed was collected by filtration, washed with benzene, and dried in vacuo to give Pd(dppf)2Cl2 (~48 g) in over 90% yield. This is pure enough for the next step, the complex can be recrystallized from chloroform/benzene.

目前市面上常見(jiàn)的，用于偶聯(lián)反應(yīng)的鈀催化劑種類很多，比如醋酸鈀、二苯基磷二茂鐵二氯化鈀、四三苯基膦鈀、二氯二三苯基膦鈀、鈀碳等等。不同種類的催化劑價(jià)格差別非常大，請(qǐng)問(wèn)它們?cè)诖呋ㄅ悸?lián)）反應(yīng)方面有什么區(qū)別呢？

作者：謝嘉欣
鏈接：https://www.zhihu.com/question/59214404/answer/162970339
來(lái)源：知乎
著作權(quán)歸作者所有。商業(yè)轉(zhuǎn)載請(qǐng)聯(lián)系作者獲得授權(quán)，非商業(yè)轉(zhuǎn)載請(qǐng)注明出處。

粗略說(shuō)說(shuō)，如果只是討論偶聯(lián)反應(yīng)（cross coupling reaction）的話，考慮偶聯(lián)反應(yīng)的基本步驟就好了。

一般偶聯(lián)反應(yīng)都從零價(jià)Pd啟動(dòng)，經(jīng)歷氧化加成（oxidative addition），轉(zhuǎn)金屬化（transmetallation），還原消除（reductive elimination）。那么對(duì)于各個(gè)步驟，不同的配體有不同的表現(xiàn)，比如調(diào)整Pd配位環(huán)境（配體電性，配體空間體積大?。┤Q于具體反應(yīng)要求。

通常富電子配體促進(jìn)氧化加成，對(duì)于難以氧化加成的底物例如氯代芳烴（見(jiàn)Greg Fu的相關(guān)工作）有很好的促進(jìn)反應(yīng)的作用，而普通的三苯基膦就不行。所以這里二（三叔丁基膦）鈀就比四（三苯基膦）鈀要好。反過(guò)來(lái)，缺電子或者大位阻膦配體能促進(jìn)還原消除，因此對(duì)于還原消除很困難或者有beta-H消除競(jìng)爭(zhēng)的偶聯(lián)反應(yīng)可使用這類型配體，還是Greg Fu的例子，sp3-sp3碳還原消除一般很難，但是這類Suzuki反應(yīng)可以用大位阻配體實(shí)現(xiàn)，既減少beta-H消除又因?yàn)槲蛔柽^(guò)大強(qiáng)迫還原消除。

此外，催化劑在反應(yīng)過(guò)程中的穩(wěn)定性也是重要考量，你不想反應(yīng)還沒(méi)開(kāi)始Pd就死了（Pd黑）對(duì)吧？所以配體的存在能穩(wěn)定零價(jià)Pd中間體，使之不聚合成Pd黑析出來(lái)。如果只是普通的偶聯(lián)反應(yīng)，比如sp2-sp2的Suzuki啊Negishi啊Kumada啊Stille啊sp-sp2的Sonogashira啊諸如此類，只要沒(méi)有特殊需求，你買(mǎi)的四（三苯基膦）鈀和你買(mǎi)的醋酸鈀再額外加三苯基膦區(qū)別并不大，因?yàn)榱銉r(jià)Pd可以由二價(jià)Pd被膦配體啊胺類有機(jī)堿啊還原生成。

其實(shí)話說(shuō)回來(lái)，主要還是配體以及pre-catalyst的抗衡離子比較重要，Pd比較次要。但是不同的pre-catalyst有性能差別一般也不好預(yù)測(cè)。能好好預(yù)測(cè)的一般只有這個(gè)催化劑的Pd是不是正電性（cationic），比如Pd（OTf）2這類帶著非配位性抗衡離子的，對(duì)于特殊的難以與Pd配位的底物有奇效。其他抗衡離子如Cl有時(shí)候又不容易掉下來(lái)于是就占著茅坑（配位點(diǎn)）不拉屎（不反應(yīng)），這時(shí)候就需要Ag鹽等這類halide scavenger了（偶聯(lián)反應(yīng)中這類情況其實(shí)很少見(jiàn)，更多見(jiàn)于C-H activation等領(lǐng)域）。但是這類Pd催化劑那么多，具體哪個(gè)cationic的Pd催化劑更好，篩了才知道。

補(bǔ)充說(shuō)明一點(diǎn)，對(duì)于C-H活化領(lǐng)域Pd催化劑也是非常常用的，而這時(shí)候因?yàn)镃MD（concerted metallation deprotonation）機(jī)理的需求，抗衡離子就多半是羧酸根了，比如常見(jiàn)的醋酸鈀（palladium acetate），新戊酸鈀（palladium pivalate），三氟乙酸鈀（palladium trifluoroacetate）等等。甚至很多情況為了優(yōu)化反應(yīng)，采用醋酸鈀作為起始催化劑，然后一頓狂篩一遍各種奇葩結(jié)構(gòu)的羧酸的也是見(jiàn)怪不怪，畢竟你沒(méi)有那么多XX酸鈀可以買(mǎi)嘛。。。

總之，如果只是做偶聯(lián)反應(yīng)，考慮到使用頻率和價(jià)格，一般醋酸鈀買(mǎi)的很多，其他的常見(jiàn)二價(jià)鈀啊多多少少能買(mǎi)就買(mǎi)，零價(jià)鈀比較常見(jiàn)就是dba（二芐叉丙酮）類（如Pd(dba)2和Pd2(dba)3等），膦配體類（如前所述）配合物等，也比較常用，至于好不好用，還是要看反應(yīng)本身。配體比較重要，所以種類也是盡量越多越好。至于Pd/C，這是非均相催化劑（之前的都是均相催化），基本只用來(lái)催化加氫或者脫氫脫鹵等。

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