Comprehensive Analysis on the Synthesis Methods of 2-Phenylindole Derivatives with Pharmacological Importance for Green Synthesis

2-Phenylindoles, as a special subset of indole compounds, stand out as some of the most promising candidates for drug development. To guide researchers toward developing new 2-phenylindole drugs in a more environmentally friendly and cost-effective manner, we have summarized and analyzed synthesis methods for 2-phenylindole over the past two decades. Our key findings are as follows: First, among the two methods discussed in this paper, the one-step method is often suitable for the synthesis of 2-phenylindole derivatives with a small amount of substitutions on both sides, whereas the indole C-2 coupling reaction is preferable for indole or C-2 benzene rings with more complex substitutions. Second, the primary challenge in synthesizing 2-phenylindole compounds lies in achieving selectivity at the indole C-2 and C-3 sites. Lastly, to achieve more efficient, economical, and environmentally friendly methods, researchers have developed new catalytic systems, including nontoxic catalysts, metal-free catalysts, recyclable metal catalysts, or nanocrystallized transition metals, as well as new methodologies such as photoinduced reactions, electrocatalytic reactions, magnetocatalytic methods, and aqueous-phase catalytic methods. These avenues may represent future research directions for chemists. In conclusion, there remains ample room for research and development in the green synthesis of 2-phenylindole derivatives.