1,1’-双(二苯基膦基)二茂铁介导的芳烃碳氢键芳基化反应制备联芳基骨架（英文）

DPPF-Mediated C―H Arylation of Arenes with Aryl Iodides for Synthesis of Biaryl Linkages

联芳基骨架的合成过去主要依赖于过渡金属催化的交叉偶联反应和碳氢键芳基化反应。近年来,碱促进的芳基卤化物与非活化芳烃的自由基芳香取代反应(BHAS)得到了广泛的关注,为合成联芳基骨架提供了更简洁的策略。在本文中,我们报道了使用叔丁醇钾作碱和电子供体,dppf(1,1’-双(二苯基膦基)二茂铁)介导的非活化芳烃与芳基碘的直接芳基化反应。在标准反应条件下,一系列具有不同取代基团的芳基碘化物和芳烃都能顺利反应,以良好的收率和区域选择性生成芳基化产物。分子内芳基化反应也可以顺利进行:该反应经历了单电子转移(SET)/引发、5-exo-trig自由基加成、扩环、去质子化和芳构化/链增长等步骤。机理研究表明,dppf骨架中的二苯基膦基团通过与叔丁醇阴离子作用提高其单电子还原能力,是顺利引发反应的关键。同时,同位素效应实验结果表明叔丁醇钾与环己二烯基自由基中间体的去质子化过程是整个反应中的决速步。

The broad existence of the biaryl linkage in bioactive organic molecules and functional materials makes it an attractive synthesis target via construction of aryl-aryl carbon bonds.Transition metal catalyzed cross-coupling reactions of two pre-functionalized aryl partners,e.g.,SuzukiMiyaura cross-coupling and Negishi cross-coupling reactions,are the main methods typically used for the construction of biaryl linkages.Since the end of the last century,transition metal catalyzed direct C―H arylation of unactivated arenes has emerged as a practical alternative to the well-established cross-coupling strategies.However,the use of transition metal catalysts and/or organometallic reagents would lead to problems,such as the disposal of waste from large-scale syntheses and the removal of heavy metal contaminants from pharmaceutical intermediates.In this regard,the base-promoted homolytic aromatic substitution(BHAS)reaction of aryl halides with unactivated arenes offers a simpler strategy for the synthesis of biaryl scaffolds,and avoids the use of transition metals.Although the BHAS reaction can proceed to a small extent without any additives,particularly at elevated temperatures,the addition of organic promoters would significantly accelerate the reaction rate and improve the overall efficiency of the process.Over the past ten years,a wide variety of N-and O-based organic promoters have been developed to promote the BHAS reaction in the presence of the tert-butoxide base.The mechanism of the BHAS reaction has been studied extensively,and is accepted as occurring via a radical chain process involving an aryl radical.However,the role and mode of initiation of most organic promoters studied remain controversial.The development of more and varied organic promoters will surely promote the mechanistic understanding and further development of the BHAS reaction.Herein,we report that 1,1’-bis(diphenylphosphino)ferrocene(dppf,or DPPF)can act as a P-based promoter to facilitate the direct arylation of unactivated arenes with aryl iodides using potassium tert-butoxide as the base and electron donor.A broad range of aryl iodides and arenes reacted smoothly under the optimized reaction conditions,giving arylated products in good yields and with high regio-selectivity.Intramolecular C―H arylation also worked well following a sequence of single electron transfer(SET)/initiation,5-exo-trig aryl radical addition,ring expansion,deprotonation,and re-aromatization/propagation.A mechanistic study indicated that the diphenylphosphino group of dppf played a vital role in the initiation step by enhancing the SET-inhibiting ability of the tert-butoxide anion.A primary kinetic isotope effect was observed in the parallel reactions between 4-methoxy-iodobenzene with benzene and deuterated benzene,implying that the deprotonation of the cyclohexadienyl radical intermediate by tert-butoxide was the ratedetermining step in the radical chain pathway.