Fleischauer Valerie E, Muñoz Iii Salvador B, Neate Peter G N, Brennessel William W, Neidig Michael L
Department of Chemistry , University of Rochester , Rochester , New York 14627 , USA . Email:
Chem Sci. 2018 Jan 8;9(7):1878-1891. doi: 10.1039/c7sc04750a. eCollection 2018 Feb 21.
While iron-NHC catalysed cross-couplings have been shown to be effective for a wide variety of reactions ( aryl-aryl, aryl-alkyl, alkyl-alkyl), the nature of the formed and reactive iron species in effective catalytic systems remains largely undefined. In the current study, freeze-trapped Mössbauer spectroscopy, and EPR studies combined with inorganic synthesis and reaction studies are utilised to define the key formed and reactive iron-NHC species in the Kumada alkyl-alkyl cross-coupling of (2-(1,3-dioxan-2-yl)ethyl)magnesium bromide and 1-iodo-3-phenylpropane. The key reactive iron species formed is identified as (IMes)Fe((1,3-dioxan-2-yl)ethyl), whereas the = 1/2 iron species previously identified in this chemistry is found to be only a very minor off-cycle species (<0.5% of all iron). Reaction and kinetic studies demonstrate that (IMes)Fe((1,3-dioxan-2-yl)ethyl) is highly reactive towards the electrophile resulting in two turnovers with respect to iron ( > 24 min) to generate cross-coupled product with overall selectivity analogous to catalysis. The high resistance of this catalytic system to β-hydride elimination of the alkyl nucleophile is attributed to its chelation to iron through ligation of carbon and one oxygen of the acetal moiety of the nucleophile. In fact, alternative NHC ligands such as SIPr are less effective in catalysis due to their increased steric bulk inhibiting the ability of the alkyl ligands to chelate. Overall, this study identifies a novel alkyl chelation method to achieve effective alkyl-alkyl cross-coupling with iron(ii)-NHCs, provides direct structural insight into NHC effects on catalytic performance and extends the importance of iron(ii) reactive species in iron-catalysed cross-coupling.
虽然铁-NHC催化的交叉偶联反应已被证明对多种反应（芳基-芳基、芳基-烷基、烷基-烷基）有效，但有效催化体系中形成的活性铁物种的性质在很大程度上仍不明确。在本研究中，利用冷冻捕获的穆斯堡尔光谱和EPR研究，结合无机合成和反应研究，来确定在（2-(1,3-二氧六环-2-基)乙基）溴化镁与1-碘-3-苯基丙烷的熊田烷基-烷基交叉偶联反应中形成的关键活性铁-NHC物种。所形成的关键活性铁物种被鉴定为(IMes)Fe((1,3-二氧六环-2-基)乙基)，而此前在该化学体系中鉴定出的自旋 = 1/2的铁物种被发现只是一种非常次要的非循环物种（占所有铁的比例<0.5%）。反应和动力学研究表明，(IMes)Fe((1,3-二氧六环-2-基)乙基)对亲电试剂具有高反应活性，相对于铁可实现两次周转（>24分钟），以生成具有与催化类似的总体选择性的交叉偶联产物。该催化体系对烷基亲核试剂的β-氢消除具有高抗性，这归因于亲核试剂缩醛部分的碳和一个氧与铁的螯合作用。事实上，诸如SIPr等其他NHC配体在催化中效果较差，因为它们增加的空间位阻抑制了烷基配体的螯合能力。总体而言，本研究确定了一种实现铁(ii)-NHC有效烷基-烷基交叉偶联的新型烷基螯合方法，提供了关于NHC对催化性能影响的直接结构见解，并扩展了铁(ii)活性物种在铁催化交叉偶联中的重要性。
