Bakas Nikki J, Sears Jeffrey D, Brennessel William W, Neidig Michael L
Department of Chemistry, B31 Hutchison Hall, University of Rochester, 120 Trustee Rd, Rochester, NY 14627, USA.
Angew Chem Int Ed Engl. 2022 Apr 4;61(15):e202114986. doi: 10.1002/anie.202114986. Epub 2022 Feb 18.
Herein, we expand the current molecular-level understanding of one of the most important and effective additives in iron-catalyzed cross-coupling reactions, N,N,N',N'-tetramethylethylenediamine (TMEDA). Focusing on relevant phenyl and ethyl Grignard reagents and slow nucleophile addition protocols commonly used in effective catalytic systems, TMEDA-iron(II)-aryl intermediates are identified via in situ spectroscopy, X-ray crystallography, and detailed reaction studies to be a part of an iron(II)/(III)/(I) reaction cycle where radical recombination with FePhBr(TMEDA) (2 ) results in selective product formation in high yield. These results differ from prior studies with mesityl Grignard reagent, where poor product selectivity and low catalytic performance can be attributed to homoleptic iron-ate species. Overall, this study represents a critical advance in how amine additives such as TMEDA can modulate selectivity and reactivity of organoiron species in cross-coupling.
在此，我们拓展了目前对铁催化交叉偶联反应中最重要且最有效的添加剂之一N,N,N',N'-四甲基乙二胺（TMEDA）的分子水平理解。聚焦于有效催化体系中常用的相关苯基和乙基格氏试剂以及缓慢亲核加成方案，通过原位光谱、X射线晶体学和详细的反应研究，确定TMEDA-铁（II）-芳基中间体是铁（II）/（III）/（I）反应循环的一部分，其中与FePhBr（TMEDA）（2）的自由基重组导致以高产率选择性地形成产物。这些结果与之前使用均三甲苯基格氏试剂的研究不同，在后者中，产物选择性差和催化性能低可归因于同配铁酸盐物种。总体而言，这项研究代表了在胺添加剂如TMEDA如何调节交叉偶联中有机铁物种的选择性和反应性方面的一项关键进展。
