A simple, efficient, cheap, and broadly applicable system for the carboxylation of benzylic bromides with carbon monoxide and water is reported. Upon simple reaction with only 2.5 wt % of Pearlman's catalyst and 10 mol % of tetrabutylammonium bromide in tetrahydrofuran at 110°C for 4 h, a range of benzylic bromides can be smoothly converted to the corresponding arylacetic acids in good to excellent yields after simple extraction and acid−base wash. The reaction was found to be broadly applicable, scalable, and could be successfully extended to the use of ex situ-generated carbon monoxide and applied to the synthesis of the nonsteroidal anti-inflammatory drug diclofenac.

A selective photochemical monochlorination of 2-fluorotoluene has been developed by a continuous flow process using two different flow reactors, one for the tuning of the conditions and the second one for the scale-up. The key reaction parameters were optimized using one-factor-at-a-time and design of experiment methods, with the goal of minimizing the formation of the dichlorinated by-product. This transformation has been performed on a multi decagram scale.