1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP) can act as both the solvent and the catalyst to promote the Pictet–Spengler reactions between tryptamine derivatives and aldehydes or activated ketones. For most substrates, removing the low boiling point HFIP by distillation directly afforded tetrahydro-β-carbolines in high yields.