Kim Byeong-Seon, Hussain Mahmud M, Norrby Per-Ola, Walsh Patrick J
P. Roy and Diana T. Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 S. 34 Street, Philadelphia, PA 19104-6323, USA;
University of Gothenburg, Department of Chemistry and Molecular Biology, Kemigården 4, #8076, SE-412 96 Göteborg, Sweden;
Chem Sci. 2014 Mar;5(3):1241-1250. doi: 10.1039/C3SC53035C.
η-Allyl palladium complexes are key intermediates in Tsuji-Trost allylic substitution reactions. It is well known that (η-1-aryl-3-alkyl substituted allyl)Pd intermediates result in nucleophilic attack at the alkyl substituted terminus. In contrast, the chemistry of (η-1,2,3-trisubstituted allyl)Pd intermediates is relatively unexplored. Herein we probe the regioselectivity with 1,2,3-trisubstituted allylic substrates in Tsuji-Trost allylic substitution reactions. DFT investigation of cationic (η-1-Ph-2-B(pin)-3-alkyl-allyl)Pd(PPh) intermediates predict that nucleophilic attack should occur preferentially on -allyls rather than the -isomers to generate benzylic substitution products under Curtin-Hammett conditions. Experimentally, systematic studies with 1,2,3-trisubstituted allylic substrates revealed that a Linear Free Energy Relationship (LFER) is observed when Charton steric parameters of the C-2 substituents are plotted against the log of the ratio of regioisomers. Bulkier C-2 substituents in 1,2,3-trisubstituted η-allyl palladium intermediates provide stronger preference for nucleophilic attack at -oriented benzylic termini. Additionally, the geometry of 1,4-elimination products supports the presence of -allyl palladium intermediates.
η-烯丙基钯配合物是铃木-特罗斯特烯丙基取代反应中的关键中间体。众所周知，（η-1-芳基-3-烷基取代烯丙基）钯中间体导致在烷基取代末端发生亲核进攻。相比之下，（η-1,2,3-三取代烯丙基）钯中间体的化学性质相对未被充分探索。在此，我们在铃木-特罗斯特烯丙基取代反应中用1,2,3-三取代烯丙基底物探究区域选择性。对阳离子（η-1-苯基-2-B（频哪醇硼酸酯）-3-烷基-烯丙基）钯（三苯基膦）中间体的密度泛函理论研究预测，在柯廷-哈梅特条件下，亲核进攻应优先发生在-烯丙基而非-异构体上，以生成苄基取代产物。实验上，对1,2,3-三取代烯丙基底物的系统研究表明，当绘制C-2取代基的查顿立体参数与区域异构体比例的对数关系图时，观察到线性自由能关系（LFER）。1,2,3-三取代η-烯丙基钯中间体中体积更大的C-2取代基对在-取向苄基末端的亲核进攻表现出更强的偏好。此外，1,4-消除产物的几何结构支持-烯丙基钯中间体的存在。
