Homocoupling of aryl halides in flow: Space integration of lithiation and FeCl₃ promoted homocoupling

Abstract

SummaryThe use of FeCl3 resulted in a fast homocoupling of aryllithiums, and this enabled its integration with the halogen–lithium exchange reaction of aryl halides in a flow microreactor. This system allows the homocoupling of two aryl halides bearing electrophilic functional groups, such as CN and NO2, in under a minute.

Technology for Continuous Production of Fine Chemicals

“…However, the integration of multistep reactions in flow provides a very fast and effective method for the coupling of two different aryl and heteroaryl bromides to give the corresponding biaryls and biheteroaryls, using the optimized catalyst PEPPSI-SIPr. This methodology was further extended to coupling with vinyl halides and oxidative homocoupling (63,64).…”

Microreactor Technology in Lithium Chemistry

“…PEPPSI-SIPr, however, serves as a good catalyst for this purpose, and the space integration provides a very fast and effective method for the coupling of two different aryl and heteroaryl bromides to give the corresponding biaryls and biheteroaryls [87]. Moreover, the method can be applied to the coupling with vinyl halides and oxidative homocoupling [88,89]. Many other examples of space integration of halogen-lithium exchange with various reactions such as carbolithiation, fluorination, borylation, and borylation followed by Suzuki-Miyaura coupling using flow microreactors have been also reported in the literature [90][91][92][93][94][95][96].…”

3. Principles of controlling reactions in flow chemistry

“…Therefore, it is important to search for a catalyst that enables the cross-coupling faster than the side reactions. The halogen/Li exchange reactions can also be integrated with homo-coupling reactions promoted by FeCl 3 [57]. An integrated flow microreactor system that consists of three micromixers (M1, M2, and M3) and three microtube reactors (R1, R2, and R3) are used for the integration of Br/Li exchange and the cross-coupling (Figure 3.31).…”