Acta Physico-Chimica Sinica ›› 2019, Vol. 35 ›› Issue (9): 1021-1026.doi: 10.3866/PKU.WHXB201811044

Special Issue: 碳氢键活化

• Article • Previous Articles     Next Articles

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

Qingbing WANG,Zhengwei GUO,Gong CHEN*(),Gang HE*()   

  • Received:2018-11-30 Accepted:2019-01-22 Published:2019-01-24
  • Contact: Gong CHEN,Gang HE E-mail:gongchen@nankai.edu.cn;hegang@nankai.edu.cn
  • Supported by:
    The project was supported by the National Natural Science Foundation of China(21672105);The project was supported by the National Natural Science Foundation of China(21725204);The project was supported by the National Natural Science Foundation of China(91753124);Natural Science Foundation of Tianjin, China(17JCYBJC19700);Natural Science Foundation of Tianjin, China(18JCZDJC32800)

Abstract:

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., Suzuki-Miyaura 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 rate-determining step in the radical chain pathway.

Key words: C―H arylation, tert-butoxide, DPPF, Radical, Biaryl synthesis

MSC2000: 

  • O643