Grupo de Lactamas y Heterociclos Bioactivos, Departamento de Química Orgánica I, Unidad Asociada al CSIC, Facultad de Química, Universidad Complutense de Madrid , 28040 Madrid, Spain.
Acc Chem Res. 2014 Mar 18;47(3):939-52. doi: 10.1021/ar4002558. Epub 2014 Jan 15.
Although gold is chemically inert as a bulk metal, the landmark discovery that gold nanoparticles can be effective catalysts has opened up new and exciting research opportunities in the field. In recent years, there has been growth in the number of reactions catalyzed by gold complexes [gold(I) and gold(III)], usually as homogeneous catalysts, because they are soft Lewis acids. In addition, alkynes and allenes have interesting reactivities and selectivities, notably their ability to produce complex structures in very few steps. In this Account, we describe our work in gold catalysis with a focus on the formation of C-C and C-O bonds using allenes and alkynes as starting materials. Of these, oxa- and carbo-cyclizations are perhaps the best known and most frequently studied. We have divided those contributions into sections arranged according to the nature of the starting material (allene versus alkyne). Gold-catalyzed carbocyclizations in allenyl C2-linked indoles, allenyl-β-lactams, and allenyl sugars follow different mechanistic pathways. The cyclization of indole-tethered allenols results in the efficient synthesis of carbazole derivatives, for example. However, the compound produced from gold-catalyzed 9-endo carbocyclization of (aryloxy)allenyl-tethered 2-azetidinones is in noticeable contrast to the 5-exo hydroalkylation product that results from allenyl sugars. We have illustrated the unusual preference for the 4-exo-dig cyclization in allene chemistry, as well as the rare β-hydride elimination reaction, in gold catalysis from readily available α-allenols. We have also observed in γ-allenols that a (methoxymethyl)oxy protecting group not only masks a hydroxyl functionality but also exerts directing effects as a controlling unit in a gold-catalyzed regioselectivity reversal. Our recent work has also led to a combined experimental and computational study on regioselective gold-catalyzed synthetic routes to 1,3-oxazinan-2-ones (kinetically controlled products) and 1,3-oxazin-2-one derivatives (thermodynamically favored) from easily accessible allenic carbamates. In addition, we discuss the direct gold-catalyzed cycloketalization of alkynyldioxolanes, as well as aminoketalization of alkynyloxazolidines. We performed labeling studies and density functional calculations to gain insight into the mechanisms of the bis-heterocyclization reactions. We also describe the controlled gold-catalyzed reactions of primary and secondary propargylic hydroperoxides with a variety of nucleophiles including alcohols and phenols, allowing the direct synthesis of β-functionalized ketones. Through computations and (18)O-labeling experiments, we discovered various aspects of the controlled reactivity of propargylic hydroperoxides with external nucleophiles under gold catalysis. The mechanism resembles a Meyer-Schuster rearrangement, but notably, the presence and geometry characteristics of the OOH functional group allow a new pathway to happen, which cannot apply to propargylic alcohols.
虽然金作为块状金属在化学上是惰性的，但金纳米粒子可以作为有效催化剂这一里程碑式的发现，为该领域开辟了新的令人兴奋的研究机会。近年来，金配合物[金（I）和金（III）]催化的反应数量有所增加，通常作为均相催化剂，因为它们是软路易斯酸。此外，炔烃和丙二烯具有有趣的反应性和选择性，尤其是它们能够在很少的步骤中产生复杂结构的能力。在本报告中，我们描述了我们在金催化方面的工作，重点是使用丙二烯和炔烃作为起始原料形成 C-C 和 C-O 键。在这些反应中，氧杂环丙烷和碳杂环丙烷的环化反应也许是最著名和最常研究的反应。我们根据起始材料的性质（丙二烯与炔烃）将这些贡献分为几节。金催化的 C2 连接吲哚、β-内酰胺和糖基丙二烯的碳环化遵循不同的反应机理。吲哚连接的丙二烯醇的环化导致咔唑衍生物的有效合成，例如。然而，与由金催化的（芳氧基）丙二烯连接的 2-氮杂环丁酮的 9-endo 碳环化产生的 5-exo 氢烷基化产物形成鲜明对比。我们说明了在金催化中丙二烯化学中不寻常的对 4-exo-dig 环化的偏好，以及在金催化中罕见的β-氢消除反应，这是由易得的α-丙二烯醇实现的。我们还在γ-丙二烯醇中观察到，甲氧基甲基氧基保护基不仅掩蔽了羟基官能团，而且作为控制单元在金催化的区域选择性反转中发挥定向作用。我们最近的工作还导致了对区域选择性金催化合成 1,3-恶唑烷-2-酮（动力学控制产物）和 1,3-恶嗪-2-酮衍生物（热力学有利产物）的实验和计算研究，这些产物可从易得的烯丙基氨基甲酸酯获得。此外，我们还讨论了炔丙基二氧戊环的直接金催化环缩酮化以及炔丙基恶唑烷的氨基缩酮化。我们进行了标记研究和密度泛函计算，以深入了解双杂环化反应的机理。我们还描述了伯和仲炔丙基过氧化物与各种亲核试剂（包括醇和酚）的可控金催化反应，允许直接合成β-官能化酮。通过计算和（18）O 标记实验，我们发现了金催化下过氧化物与外部亲核试剂的可控反应性的各个方面。该机理类似于 Meyer-Schuster 重排，但值得注意的是，OOH 官能团的存在和几何特征允许发生新的途径，而该途径不适用于炔丙醇。
