Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C (Denmark).
Chemistry. 2013 Dec 23;19(52):17926-38. doi: 10.1002/chem.201303384. Epub 2013 Nov 21.
Reaction conditions for the three-component synthesis of aryl 1,3-diketones are reported applying the palladium-catalyzed carbonylative α-arylation of ketones with aryl bromides. The optimal conditions were found by using a catalytic system derived from [Pd(dba)2] (dba=dibenzylideneacetone) as the palladium source and 1,3-bis(diphenylphosphino)propane (DPPP) as the bidentate ligand. These transformations were run in the two-chamber reactor, COware, applying only 1.5 equivalents of carbon monoxide generated from the CO-releasing compound, 9-methylfluorene-9-carbonyl chloride (COgen). The methodology proved adaptable to a wide variety of aryl and heteroaryl bromides leading to a diverse range of aryl 1,3-diketones. A mechanistic investigation of this transformation relying on 31P and 13C NMR spectroscopy was undertaken to determine the possible catalytic pathway. Our results revealed that the combination of [Pd(dba)2] and DPPP was only reactive towards 4-bromoanisole in the presence of the sodium enolate of propiophenone suggesting that a [Pd(dppp)(enolate)] anion was initially generated before the oxidative-addition step. Subsequent CO insertion into an [Pd(Ar)(dppp)(enolate)] species provided the 1,3-diketone. These results indicate that a catalytic cycle, different from the classical carbonylation mechanism proposed by Heck, is operating. To investigate the effect of the dba ligand, the Pd0 precursor, [Pd(η3-1-PhC3H4)(η5-C5H5)], was examined. In the presence of DPPP, and in contrast to [Pd(dba)2], its oxidative addition with 4-bromoanisole occurred smoothly providing the [PdBr(Ar)(dppp)] complex. After treatment with CO, the acyl complex [Pd(CO)Br(Ar)(dppp)] was generated, however, its treatment with the sodium enolate led exclusively to the acylated enol in high yield. Nevertheless, the carbonylative α-arylation of 4-bromoanisole with either catalytic or stoichiometric [Pd(η3-1-PhC3H4)(η5-C5H5)] over a short reaction time, led to the 1,3-diketone product. Because none of the acylated enol was detected, this implied that a similar mechanistic pathway is operating as that observed for the same transformation with [Pd(dba)2] as the Pd source.
报道了应用钯催化酮的羰基α-芳基化反应，由酮与芳基溴化物三组分合成芳基 1,3-二酮的反应条件。通过使用源自[Pd(dba)2]（dba=二苄叉丙酮）的催化体系作为钯源和 1,3-双（二苯基膦）丙烷（DPPP）作为双齿配体，找到了最佳条件。这些转化在 COware 双室反应器中进行，仅使用从 CO 释放化合物 9-甲基芴-9-羰基氯（COgen）生成的 1.5 当量的一氧化碳。该方法适用于各种芳基和杂芳基溴化物，得到了多种芳基 1,3-二酮。通过 31P 和 13C NMR 光谱学对这种转化进行了机理研究，以确定可能的催化途径。我们的结果表明，在丙酰苯的烯醇钠存在下，[Pd(dba)2]和 DPPP 的组合仅对 4-溴苯甲醚有反应性，这表明在氧化加成步骤之前，最初生成了[Pd(dppp)(烯醇化物)]阴离子。随后，CO 插入到[Pd(Ar)(dppp)(烯醇化物)]物种中，得到 1,3-二酮。这些结果表明，正在运行不同于 Heck 提出的经典羰基化机制的催化循环。为了研究 dba 配体的影响，研究了 Pd0 前体[Pd(η3-1-PhC3H4)(η5-C5H5)]。在 DPPP 的存在下，与[Pd(dba)2]相反，其与 4-溴苯甲醚的氧化加成反应顺利进行，得到[PdBr(Ar)(dppp)]配合物。用 CO 处理后，生成了[Pd(CO)Br(Ar)(dppp)]酰基配合物，但用烯醇钠处理时，仅以高产率得到酰化的烯醇。然而，无论是使用催化量还是化学计量量的[Pd(η3-1-PhC3H4)(η5-C5H5)]，在短反应时间内，4-溴苯甲醚的羰基α-芳基化反应均导致 1,3-二酮产物生成。由于没有检测到酰化的烯醇，这意味着与使用[Pd(dba)2]作为钯源的相同转化一样，正在运行类似的机理途径。
