Organic Chemistry & Catalysis, Utrecht University, Padualaan 8, 3584, CH, Utrecht, NL.
Dalton Trans. 2010 Nov 21;39(43):10338-51. doi: 10.1039/c0dt00674b.
The copper-mediated aromatic nucleophilic substitution reactions developed by Fritz Ullmann and Irma Goldberg required stoichiometric amounts of copper and very high reaction temperatures. Recently, it was found that addition of relatively cheap ligands (diamines, aminoalcohols, diketones, diols) made these reactions truly catalytic, with catalyst amounts as low as 1 mol% or even lower. Since these catalysts are homogeneous, it has opened up the possibility to investigate the mechanism of these modified Ullmann reactions. Most authors agree that Cu(I) is the true catalyst even though Cu(0) and Cu(II) catalysts have also shown to be active. It should be noted however that Cu(I) is capable of reversible disproportionation into Cu(0) and Cu(II). In the first step, the nucleophile displaces the halide in the LnCu(I)X complex forming LnCu(I)ZR (Z = O, NR′, S). Quite a number of mechanisms have been proposed for the actual reaction of this complex with the aryl halide: 1. Oxidative addition of ArX forming a Cu(III) intermediate followed by reductive elimination; 2. Sigma bond metathesis; in this mechanism copper remains in the Cu(II) oxidation state; 3. Single electron transfer (SET) in which a radical anion of the aryl halide is formed (Cu(I)/Cu(II)); 4. Iodine atom transfer (IAT) to give the aryl radical (Cu(I)/Cu(II)); 5. π-complexation of the aryl halide with the Cu(I) complex, which is thought to enable the nucleophilic substitution reaction. Initially, the radical type mechanisms 3 and 4 where discounted based on the fact that radical clock-type experiments with ortho-allyl aryl halides failed to give the cyclised products. However, a recent DFT study by Houk, Buchwald and co-workers shows that the modified Ullmann reaction between aryl iodide and amines or primary alcohols proceeds either via an SET or an IAT mechanism. Van Koten has shown that stalled aminations can be rejuvenated by the addition of Cu(0), which serves to reduce the formed Cu(II) to Cu(I); this also corroborates a Cu(I)/Cu(II) mechanism. Thus the use of radical clock type experiments in these metal catalysed reactions is not reliable. DFT calculations from Hartwig seem to confirm a Cu(I)/Cu(III) type mechanism for the amidation (Goldberg) reaction, although not all possible mechanisms were calculated.
由弗里茨·乌尔曼和伊尔玛·戈德堡开发的铜介导的芳香亲核取代反应需要化学计量的铜和非常高的反应温度。最近，人们发现，添加相对便宜的配体（二胺、氨基醇、二酮、二醇）可以使这些反应真正催化，催化剂用量低至 1mol%，甚至更低。由于这些催化剂是均相的，因此有可能研究这些改良的乌尔曼反应的机制。大多数作者都认为 Cu(I)是真正的催化剂，尽管 Cu(0)和 Cu(II)催化剂也显示出活性。然而，应该注意的是，Cu(I)能够可逆地歧化为 Cu(0)和 Cu(II)。在第一步中，亲核试剂取代 LnCu(I)X 配合物中的卤化物，形成 LnCu(I)ZR（Z=O、NR'、S）。对于该配合物与芳基卤化物的实际反应，已经提出了许多机制：1. ArX 的氧化加成形成 Cu(III)中间体，然后进行还原消除；2. σ键复分解；在这种机制中，铜保持在 Cu(II)氧化态；3. 单电子转移（SET），其中芳基卤化物形成自由基阴离子（Cu(I)/Cu(II)）；4. 碘原子转移（IAT），生成芳基自由基（Cu(I)/Cu(II)）；5. 芳基卤化物与 Cu(I)配合物的π-络合，这被认为能够使亲核取代反应发生。最初，根据邻烯基芳基卤化物的自由基钟型实验未能得到环化产物的事实，排除了 3 和 4 种自由基型机制。然而，Houk、Buchwald 和同事最近的 DFT 研究表明，芳基碘化物与胺或伯醇之间的改良乌尔曼反应可以通过 SET 或 IAT 机制进行。Van Koten 已经表明，通过添加 Cu(0)可以使停滞的胺化反应恢复活力，Cu(0)用于将形成的 Cu(II)还原为 Cu(I)；这也证实了 Cu(I)/Cu(II)机制。因此，在这些金属催化反应中使用自由基钟型实验是不可靠的。Hartwig 的 DFT 计算似乎证实了酰胺化（戈德堡）反应的 Cu(I)/Cu(III)型机制，尽管并非所有可能的机制都进行了计算。
