A Structure–Activity Study of Ni-Catalyzed Alkyl–Alkyl Kumada Coupling. Improved Catalysts for Coupling of Secondary Alkyl Halides

A structure–activity study was carried out for Ni catalyzed alkyl–alkyl Kumada-type cross coupling reactions. A series of new nickel(II) complexes including those with tridentate pincer bis(amino)amide ligands (RN2N) and those with bidentate mixed amino-amide ligands (RNN) were synthesized and structurally characterized. The coordination geometries of these complexes range from square planar, tetrahedral, to square pyramidal. The complexes had been examined as precatalysts for cross coupling of nonactivated alkyl halides, particularly secondary alkyl iodides, with alkyl Grignard reagents. Comparison was made to the results obtained with the previously reported Ni pincer complex [(MeN2N)NiCl]. A transmetalation site in the precatalysts is necessary for the catalysis. The coordination geometries and spin-states of the precatalysts have a small or no influence. The work led to the discovery of several well-defined Ni catalysts that are significantly more active and efficient than the pincer complex [(MeN2N)NiCl] for the coupling of secondary alkyl halides. The best two catalysts are [(HNN)Ni(PPh3)Cl] and [(HNN)Ni(2,4-lutidine)Cl]. The improved activity and efficiency was attributed to the fact that phosphine and lutidine ligands in these complexes can dissociate from the Ni center during catalysis. The activation of alkyl halides was shown to proceed via a radical mechanism.

本研究针对镍催化的烷基-烷基熊田型交叉偶联反应开展了构效关系研究，合成并结构表征了一系列新型镍(II)配合物，其中包括搭载三齿钳形双(氨基)酰胺配体（RN2N）的配合物以及搭载双齿混合氨基-酰胺配体（RNN）的配合物。这类配合物的配位几何构型涵盖平面正方形、四面体与四方锥三种类型。随后将上述配合物作为预催化剂，应用于未活化烷基卤化物（尤其是二级烷基碘化物）与烷基格氏试剂的交叉偶联反应，并与此前报道的钳形镍配合物[(MeN2N)NiCl]的催化结果进行对照。研究表明，预催化剂需具备转金属化位点方可实现有效催化，其配位几何构型与自旋态对催化活性仅存在微弱影响甚至无显著作用。本工作最终发现数种结构明确的镍催化剂，其用于二级烷基卤化物偶联反应时的活性与效率均显著优于[(MeN2N)NiCl]，其中催化性能最优的两款催化剂为[(HNN)Ni(PPh3)Cl]与[(HNN)Ni(2,4-二甲基吡啶)Cl]。上述催化剂活性与效率的提升，可归因于其配体中的三苯基膦（PPh3）与2,4-二甲基吡啶可在催化过程中从镍中心解离，进一步实验证实烷基卤化物的活化过程遵循自由基机理。