Stereochemistry of the Reactions between Palladacycle Complexes and Primary Alkyl Iodides

As an important elementary step in organometallic chemistry, the alkylation reaction of palladacycle complexes and alkyl halides has attracted much attention in recent years due to their presence as a key step in palladium-catalyzed C–H alkylation reactions. In principle, several alkylation mechanisms, such as the stereoinvertive SN2-type mechanism and the stereoretentive oxidative addition mechanism, can be operative, and mechanistic insights can be obtained from the stereochemical outcomes of these alkylation reactions. Previous stereochemical investigations on the alkylation reaction of palladacycle complexes mainly focused on the use of chiral secondary alkyl halides as stereochemical probes, leaving more synthetically relevant primary alkyl iodides untouched. In this work, deuterium-labeled primary alkyl iodides were selected as a stereochemical probe, and their reaction with C,C- and C,N-type palladacycle complexes, namely, Catellani-type palladacycle intermediates and directing group (DG)-coordinated palladacycle complexes, were investigated both experimentally and computationally to elucidate the alkylation mechanism. We found that the C,C-ligated palladacycle intermediates undergo alkylation through the SN2-type mechanism, while the C,N-ligated 8-aminoquinoline-derived palladacycle complex favors a stereoretentive oxidative addition mechanism. In addition, the 2-phenylpyridine-derived C,N-type palladacycle dimer complex was found to react through the SN2-type mechanism due to its stable dimer structure and the d8–d8 interaction between two palladium atoms.作为有机金属化学中的重要基元步骤，钯环配合物与烷基卤化物的烷基化反应近年来备受关注，因其是钯催化C–H烷基化反应的关键步骤。理论上，多种烷基化反应机制均可发挥作用，例如构型翻转型SN2型机制与构型保持型氧化加成机制，通过这些烷基化反应的立体化学结果可获得机理层面的认知。此前针对钯环配合物烷基化反应的立体化学研究，主要以手性二级烷基卤化物作为立体化学探针，尚未涉及合成应用中更具相关性的一级烷基碘化物。本研究选用氘标记的一级烷基碘化物作为立体化学探针，针对C,C-型与C,N-型钯环配合物——即Catellani型钯环中间体与导向基团（DG）配位的钯环配合物——开展了实验与计算研究，以阐明其烷基化反应机制。我们发现，C,C配位的钯环中间体通过SN2型机制进行烷基化反应，而C,N配位的8-氨基喹啉衍生钯环配合物则更倾向于采用构型保持型氧化加成机制。此外，2-苯基吡啶衍生的C,N型钯环二聚体配合物，因其稳定的二聚体结构以及两个钯原子间的d8–d8相互作用，通过SN2型机制发生反应。