Laboratori de Química Orgànica, Facultat de Farmàcia, and Institut de Biomedicina, Universitat de Barcelona, 08028-Barcelona, Spain.
J Org Chem. 2012 Nov 16;77(22):10272-84. doi: 10.1021/jo301924e. Epub 2012 Nov 5.
An extensive joint experimental-computational density functional theory (DFT) study has been carried out to gain insight into the factors that control the chemoselectivity (i.e., acylation vs α-arylation reaction) of palladium-catalyzed cyclizations of (2-iodoanilino)-aldehydes. To this end, the nature of the tethers joining the aniline nitrogen and the aldehyde moiety, different palladium precatalysts and reaction conditions (base and temperature), as well as different additives (mono- and bidendate ligands) has been explored. The adequate selection of these variables allows for the control of the selectivity of the process. Thus, (2-iodoanilino)-aldehydes generally lead to the formation of nucleophilic addition derived products when Cs(2)CO(3)/Et(3)N is used as base. In contrast, the use of stronger bases like K(t)OBu (in the presence of PhOH) mainly forms α-arylation reaction products. The different reaction pathways leading to the experimentally observed reaction products have been studied by means of computational tools.
我们进行了广泛的联合实验-计算密度泛函理论（DFT）研究，以深入了解控制钯催化（2-碘代苯胺基）-醛环化反应的化学选择性（即酰化与α-芳基化反应）的因素。为此，我们探讨了连接苯胺氮和醛部分的键的性质、不同的钯前催化剂和反应条件（碱和温度）以及不同的添加剂（单齿和双齿配体）。这些变量的适当选择可以控制反应的选择性。因此，当使用 Cs(2)CO(3)/Et(3)N 作为碱时，（2-碘代苯胺基）-醛通常会生成亲核加成衍生产物。相比之下，使用更强的碱（如 K(t)OBu（在 PhOH 存在下））主要形成α-芳基化反应产物。通过计算工具研究了导致实验观察到的反应产物的不同反应途径。
