过渡金属催化的偶联反应已成为有机化学中构建碳碳键和碳杂键的重要方法。在此领域中，大部分的报道都选用卤代物作为亲电试剂；然而近年来逐渐兴起的含氧型亲电试剂的交叉偶联反应正越来越引起人们的关注。原因在于：首先，含氧型亲电试剂的偶联产物的排放（即离去基团）与卤代物偶联相比，有毒副产物更少，反应的可持续性得以提升。其次，在许多情况下，各类制备含氧型亲电试剂的原料来源丰富（醇、醛、酮、酚等）且制备方法成熟，产率高，操作简便易行，成本较低。再者，含氧型亲电试剂与不同的卤素往往有着不同的反应性，利用这些活性差异，可以实现选择性偶联，进而实施交替型连续化偶联，为合成复杂的目标化合物提供新的路径。 尽管含氧型亲电试剂拥有明显的优势，但到目前为止，它们参与的偶联主要由Pd或Ni 催化完成的。由于钯价格高，镍毒性大，Fe催化因而受到人们的青睐。遗憾的是，Fe催化含氧型亲电试剂的偶联反应多局限于C(sp2)? C(sp3)型偶联，相应的C(sp2)? C(sp2)型偶联还存在不少的挑战。 本论文以铁催化下含氧型亲电试剂与芳族格氏试剂的偶联为研究目标，旨在克服这类铁催化C(sp2)? C(sp2)型偶联目前存在的不足，如官能团耐受性差，底物适用范围窄，特别是烯醇酯芳基化立体控制性差等缺点，从而建立铁催化下含氧型亲电试剂的广谱型联芳偶联和烯醇衍生物的立体选择性芳基化反应。 具体的工作如下所示： (1) 在本课题组已建立芳基卤代物偶联的基础上，探索并建立了铁催化下酚类含氧亲电试剂与芳基格氏试剂的反应。实验表明，反应具有高的广谱性和官能团耐受性。各种含官能团或普通酚类的对甲苯磺酸酯，胺基磺酸酯和胺基甲酸酯类化合物可与普通芳基格氏试剂及含官能团芳基格氏试剂在FeCl3/NHC /PhOM/Ti(OEt)4 催化下顺利偶联。 (2) 比较了三类含氧亲电试剂与卤原子的反应活性，探明活性顺序为：ArI> ArBr > ArCl > ArOTs, ArOSO2NMe2, ArOCONMe2，并利用这一活性顺序，成功地通过选择性交替双芳基化合成了药物anidulafungin的关键中间体。 (3) 探索并建立了（E）-型烯醇磺酸酯在铁催化下与芳基格氏试剂的构型保持型芳基化反应的最佳条件，并合成了4个 E-芳基化产物。 (4) 探索并建立了具有挑战性的（Z）-型烯醇磺酸酯与芳基格氏试剂的构型保持型芳基化反应的反应条件。实验表明，由于热力学不稳定的原因，（Z）-型构底物很易在常温下发生构型异构化。通过大量的探索，建立了首个0 oC下铁催化的（Z）-型烯醇磺酸酯的构型保持型芳基化反应；并合成了6个 Z-芳基化产物。 (5) 利用以上两个反应，首次采用铁催化的立体控制型芳基化反应合成了（Z）与（E）-型抗癌药物他莫昔芬（Tamoxifen）和抗抑郁药物齐美利定（Zimelidine）的前体，为这两个药物的廉价环保型生产提供了新选择。 (6) 初步探索铁催化下烯醇醋酸酯的芳基化反应。

The transition-metal-catalyzed coupling reaction has become an important method to construct carbon-carbon bond and carbon-heteroatom bond in organic synthesis. In this field, most of reported couplings use alkyl or aryl halides as electrophilic reagents. However, in recent years, the cross-coupling reaction of C?O based electrophilic reagents is attracting more and more attention. The reasons include: (1) the coupling of the C?O based electrophile often provides less toxic by-products compared with the coupling of halides; (b) in many cases, the raw materials for the preparation of C?O based electrophiles are abundant (alcohols, aldehydes, ketones, phenols, etc.), and the preparation methods are mature with high yield, simple operation and low cost. (c) C?O based electrophiles often demonstrate different reactivity with various halogens, and these activity differences can be utilized to achieve selective couplings, which often enable iterative di or multi alkylations or arylations, and provide a new path for the synthesis of complex target compounds. Although C?O based electrophiles have obvious advantages, so far their couplings are mainly catalyzed by Pd or Ni. Due to palladium's high price and nickel's high toxicity, Fe catalysis is highly desired. Unfortunately, Fe-catalyzed coupling of this type of electrophiles is mostly limited to C(sp2)?C(sp3) coupling, and the corresponding C(sp2)?C(sp2) coupling still faces many challenges. In this paper, the Fe-catalyzed coupling of C?O based electrophiles and aryl Grignard reagent is taken as the research objective. The aim is to overcome the known shortcomings of the this iron-catalyzed coupling, such as poor functional group tolerance, narrow substrate scope, especially the poor stereocontrol of arylation of enol esters, and so as to establish a general Fe-catalyzed arylation of C?O based electrophiles and stereoselective arylation of enol derivatives. The work is summarized as follows: (1) On the basis of the protocol for the couplings of aryl halides established by our research group, the Fe-catalyzed coupling between aryl C?O based electrophiles and aryl Grignard reagents was explored and established. Our experiment shows that the reaction has high broad-scope and functional group tolerance. Various common or functionalized ArOTs, ArOSO2NMe2 and ArOCONMe2 can be successfully coupled with common or functionalized aryl Grignard reagents under the catalysis of FeCl3/NHC /PhOM/Ti(OEt)4. (2) The reactivity of three kinds of C?O based electrophiles and halogen atoms were compared, and the order of proved activity was ArI> ArBr > ArCl > ArOTs, ArOSO2NMe2 and ArOCONMe2. Taking advantage of this reactivity sequence, a key intermediate for anidulafungin was synthesized via an orthogonal coupling. strategy. (3) The optimal conditions for the Fe-catalyzed arylation reaction of (E)-enol sulfonates with aryl Grignard reagents were explored and established 4 E-arylated products were synthesized. (4) The optimal conditions of the Fe-catalyzed challenging arylation of (Z)-enol sulfonates with aryl Grignard reagents were explored and established. Our experiments show that due to thermodynamic instability, the (Z)-type substrate is prone to configurational isomerization even at room temperature. The first Fe-catalyzed arylation of (Z) enol sulfonate catalyzed at 0 oC was established 6 Z- arylated products were synthesized. (5) Based the above two reactions, the precursors of (Z-) and (E)-type anticancer drugs Tamoxifen and anti-depressant drug Zimelidine were synthesized for the first time using our iron-catalyzed stereo-controlled arylation reaction, providing a new option for the cheap and environmentally friendly production of these two drugs. (6) The Fe-catalyzed arylation of enol acetate was preliminarily explored.