Akkarasamiyo Sunisa, Sawadjoon Supaporn, Orthaber Andreas, Samec Joseph S M
Department of Organic Chemistry, Stockholm University, 106 91, Stockholm, Sweden.
Department of Chemistry, Ångström Laboratories, Uppsala University, Box 523, 75120, Uppsala, Sweden.
Chemistry. 2018 Mar 7;24(14):3488-3498. doi: 10.1002/chem.201705164. Epub 2018 Jan 12.
Palladium-catalyzed allylic substitution of non-derivatized enantioenriched allylic alcohols with a variety of uncharged N-, S-, C- and O-centered nucleophiles using a bidentate BiPhePhos ligand is described. A remarkable effect of the counter ion (X) of the XPd[κ -BiPhePhos][η -C H ] was observed. When ClPd[κ -BiPhePhos][η -C H ] (complex I) was used as catalyst, non-reproducible results were obtained. Study of the complex by X-ray crystallography, P NMR spectroscopy, and ESI-MS showed that a decomposition occurred where one of the phosphite ligands was oxidized to the corresponding phosphate, generating ClPd[κ -BiPhePhosphite-phosphate][η -C H ] species (complex II). When the chloride was exchanged to the weaker coordinating OTf counter ion the more stable Pd[κ -BiPhePhos][η -C H ] +[OTf] (complex III) was formed. Complex III performed better and gave higher enantiospecificities in the substitution reactions. Complex III was evaluated in Tsuji-Trost reactions of stereogenic non-derivatized allylic alcohols. The desired products were obtained in good to excellent yields (71-98 %) and enantiospecificities (73-99 %) for both inter- and intramolecular substitution reactions with only water generated as a by-product. The methodology was applied to key steps in total synthesis of (S)-cuspareine and (+)-lentiginosine. A reaction mechanism involving a palladium hydride as a key intermediate in the activation of the hydroxyl group is proposed in the overall transformation.
本文描述了使用双齿联苯膦配体，钯催化未衍生化的对映体富集烯丙醇与各种中性的以氮、硫、碳和氧为中心的亲核试剂进行的烯丙基取代反应。观察到XPd[κ-联苯膦][η-C₃H₅]抗衡离子(X)的显著影响。当使用ClPd[κ-联苯膦]η-C₃H₅作为催化剂时，得到不可重复的结果。通过X射线晶体学、³¹P NMR光谱和ESI-MS对该配合物的研究表明，发生了分解，其中一个亚磷酸酯配体被氧化为相应的磷酸酯，生成了ClPd[κ-联苯膦亚磷酸酯-磷酸酯][η-C₃H₅]物种(配合物II)。当将氯离子换成配位较弱的OTf抗衡离子时，形成了更稳定的Pd[κ-联苯膦][η-C₃H₅]OTf。配合物III表现更好，在取代反应中给出了更高的对映体选择性。在立体异构的未衍生化烯丙醇的辻-特罗斯特反应中对配合物III进行了评估。对于分子间和分子内取代反应，所需产物均以良好至优异的产率(71-98%)和对映体选择性(73-99%)得到制备，仅生成水作为副产物。该方法应用于(S)-库斯帕林和(+)-扁豆苷全合成的关键步骤。在整个转化过程中，提出了一种涉及钯氢化物作为羟基活化关键中间体的反应机理。
