Development of\na Safer Continuous Flow Process for\nB<sub>2</sub>(OH)<sub>4</sub>‑Mediated Chemoselective Reduction\nof Nitroarenes to Anilines

Tetrahydroxydiboron\n[B<sub>2</sub>(OH)<sub>4</sub>] is\na chemoselective\nreducing reagent for nitro reductions in the presence of other labile\nfunctional groups. However, there are significant process safety challenges\nassociated with the application of this reducing reagent, including\nrapid heat release and thermal instability of B<sub>2</sub>(OH)<sub>4</sub> in aprotic polar solvents. Herein, we report the development\nof a safer continuous flow process applying B<sub>2</sub>(OH)<sub>4</sub>-mediated chemoselective nitro reduction conditions. The safety\nchallenges were addressed by employing continuous flow technology\nalong with identifying a suitable protic cosolvent EtOH. Functional\ngroup tolerance toward cyano groups, halides, carboxylic acids, olefins,\nimines, and benzylic alcohols was demonstrated in flow with higher\nreaction yield compared to that in batch synthesis. The modified reaction\nconditions provide a potentially scalable approach to widespread applications\nof this key transformation for the generation of highly functionalized\ndiversified aniline derivatives.