Highly Productive Flow Synthesis for Lithiation, Borylation, and/or Suzuki Coupling Reaction

Abstract

The efficient synthesis of aromatic boronic acids was achieved by increasing the concentration, flow rate, and mixer diameter to prevent clogging. A 1 h synthesis actually produced 180 g of boronic acid. The real-time analysis of the reaction solution was investigated using in-line analyzers suitable for high flow rates. Additives were also studied to accelerate the Suzuki coupling reaction of the boronic acids. Integrated one-flow reactions combining boronic acid synthesis and Suzuki coupling produced pharmaceutical precursors in 97−143 s.

Expanding the Scope of C-Glycoside Synthesis from Unstable Organolithium Reagents Using Flow Microreactors

“…To investigate the effect of mixing on the yield, we evaluated the dependence of the yield on the flow rate (Figure ). A previous study demonstrated that low flow rates resulted in low mixing efficiency and reaction yield. ,, Figure shows a dramatic decrease in the yield of 4a below 8 mL min –1 . HPLC analysis revealed that the low yields were caused by low conversion of the substrates resulting from slow mixing.…”