Department of Chemistry, University of Rochester , Rochester, New York 14627, United States.
J Am Chem Soc. 2017 May 24;139(20):6988-7003. doi: 10.1021/jacs.7b02363. Epub 2017 May 16.
Iron-catalyzed cross-coupling reactions using alkynyl nucleophiles represent an attractive approach for the incorporation of alkynyl moieties into organic molecules. In the present study, a multitechnique approach combining inorganic spectroscopic methods, inorganic synthesis, and reaction studies is applied to iron-SciOPP catalyzed alkynyl-alkyl cross-couplings, providing the first detailed insight into the effects of variation from sp- to sp-hybridized nucleophiles on iron speciation and reactivity. Reaction studies demonstrate that reaction of FeBr(SciOPP) with 1 equiv (triisopropylsilyl)ethynylmagnesium bromide (TIPS-CC-MgBr) leads to a distribution of mono-, bis-, and tris-alkynylated iron(II)-SciOPP species due to rapid alkynyl ligand redistribution. While solvents such as THF promote these complex redistribution pathways, nonpolar solvents such as toluene enable increased stabilization of these iron species and further enabled assessment of their reactivity with electrophile. While the tris-alkynylated iron(II)-SciOPP species was found to be unreactive with the cycloheptyl bromide electrophile over the average turnover time of catalysis, the in situ formed neutral mono- and bis-alkynylated iron(II)-SciOPP complexes are consumed upon reaction with the electrophile with concomitant generation of cross-coupled product at catalytically relevant rates, indicating the ability of one or both of these species to react selectively with the electrophile. The nature of the reaction solvent and Grignard reagent addition rate were found to have broader implications in overall reaction selectivity, reaction rate, and accessibility of off-cycle iron(I)-SciOPP species. Additionally, the effects of steric substitution of the alkynyl Grignard reagent on catalytic performance were investigated. Fundamental insight into iron speciation and reactivity with alkynyl nucleophiles reported herein provides an essential foundation for the continued development of this important class of reactions.
铁催化的交叉偶联反应使用炔基亲核试剂代表了一种将炔基部分引入有机分子的有吸引力的方法。在本研究中，结合无机光谱方法、无机合成和反应研究的多技术方法应用于铁-SciOPP 催化的炔基-烷基交叉偶联，首次详细了解了从 sp 到 sp 杂化亲核试剂的变化对铁形态和反应性的影响。反应研究表明，FeBr(SciOPP)与 1 当量（三异丙基硅基）乙炔基镁溴化物（TIPS-CC-MgBr）反应导致单、双和三炔基化铁（II）-SciOPP 物种的分布，由于炔基配体的快速重新分布。虽然像 THF 这样的溶剂促进了这些复杂的重新分布途径，但像甲苯这样的非极性溶剂能够增加这些铁物种的稳定性，并进一步能够评估它们与亲电试剂的反应性。虽然三炔基化铁（II）-SciOPP 物种被发现与环己基溴化物亲电试剂在催化平均周转时间内不反应，但在原位形成的中性单和双炔基化铁（II）-SciOPP 配合物在与亲电试剂反应时被消耗，同时以催化相关的速率生成交叉偶联产物，表明一种或两种这些物种都能够选择性地与亲电试剂反应。反应溶剂的性质和格氏试剂的添加速率对总体反应选择性、反应速率和非循环铁（I）-SciOPP 物种的可及性具有更广泛的影响。此外，还研究了炔基格氏试剂的空间位阻取代对催化性能的影响。本文报道的关于铁形态和与炔基亲核试剂反应性的基本见解为这一重要反应类别的持续发展提供了重要基础。
