Construction of CF₂ moieties in FDA-approved drugs (2016–2025): industrial routes, mechanisms, and scale-up considerations

• Wenyan Yao,
• Huanhuan Zhang,
• Xiaolong Yang and
• Feng Liu

Beilstein J. Org. Chem. 2026, 22, 1122–1150, doi:10.3762/bjoc.22.91

• drugs, from strategic design to scale-up evaluation. Keywords: difluoromethylene group (-CF2-); difluoromethyl group (-CF2H); FDA-approved drugs; fluorination methods; process scale-up; Introduction In recent years, the CF2 group has demonstrated unique advantages in drug discovery and clinical

• design and process scale-up of future CF2-containing molecules. To help readers distinguish between routes that have been demonstrated at production scale and those reported only at the laboratory level, the following visual conventions are adopted in the schemes. Industrial steps or routes for which

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• . [6], and Sagmeister et al. [7]. The first two offer valuable perspectives on chemical reaction optimization, particularly focusing on process scale-up, while the latter discusses the potential of flow platforms for self-optimization reactions. Additionally, we refer the readers to the following