Once Upon a Time Without DMF: Greener Paths in Peptide and Organic Synthesis

N,N-Dimethylformamide (DMF) has been a cornerstone solvent in both peptide and organic synthesis due to its excellent solubilizing properties and chemical stability. However, its use has raised significant health and environmental concerns. DMF is classified as a substance of very high concern (SVHC) by the European Chemicals Agency (ECHA) due to its reproductive toxicity and potential for skin absorption, leading to liver damage upon prolonged exposure. Consequently, restrictions on its use have been introduced, encouraging the scientific community to seek safer, more sustainable alternatives. This review provides a comprehensive analysis of the existing literature on alternative solvents to DMF, identifying current gaps or problems, and offering recommendations for future research.