Recent Advances in Continuous-Flow Reactions Using Metal-Free Homogeneous Catalysts

• Naoto Sugisawa^1,2
• Hiroyuki Nakamura^>1
• Shinichiro Fuse³

• ¹Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan
• ²School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8501, Japan
• ³Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya 464-8601, Japan

Developments that result in high-yielding, low-cost, safe, scalable, and less-wasteful processes are the most important goals in synthetic organic chemistry. Continuous-flow reactions have garnered much attention due to many advantages over conventional batch reactions that include precise control of short reaction times and temperatures, low risk in handling dangerous compounds, and ease in scaling up synthesis. Combinations of continuous-flow reactions with homogeneous, metal-free catalysts further enhances advantages that include low-cost and ready availability, low toxicity, higher stability in air and water, and increased synthetic efficiency due to the avoidance of the time-consuming removal of toxic metal traces. This review summarizes recently reported continuous-flow reactions using metal-free homogeneous catalysts and classifies them either as acidic catalysts, basic catalysts, or miscellaneous catalysts. In addition, we compare the results between continuous-flow conditions and conventional batch conditions to reveal the advantages of using flow reactions with metal-free homogeneous catalysts.

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