Efficient synthesis of m-terphenyl compounds in continuous flow utilizing organomagnesium

Abstract

As a crucial component of catalytic ligands, the synthesis of 1-bromo-3,5-diarylbenzene compounds holds significant value. Herein, we have reported a continuous-flow method for the synthesis of diverse 1-bromo-3,5-diarylbenzene compounds. A novel organomagnesium reagent was prepared via halogen-magnesium exchange between iPrMgCl·LiCl and 2,4,6-tribromoiodobenzene, followed by sequential C–C bond formation with aryl Grignard reagents to afford terphenyl Grignard reagents within 468 s. These intermediates exhibited broad reactivity towards diverse electrophiles and could be directly quenched to afford a series of 1-bromo-3,5-diarylbenzene compounds (16 examples) with isolated yields of 66–90%. This method obviates the need for large excesses of aryl Grignard reagents, avoids the use of noble metal catalysts, and simplifies purification via direct recrystallization. Moreover, a high-performance scale-up synthesis of the precursor for the catalytic ligand was smoothly carried out, demonstrating its practical utility.

Graphical abstract

The generation of a novel organomagnesium reagent in a continuous flow reactor and its reaction with aryl Grignard reagents is reported. A series of m-terphenyl compounds have been synthesized, achieving good yields of up to 90% across 21 examples.