MTTP: A Powerful Electrophilic Trifluoromethylthiolating Reagent Applicable to Electron-deficient Aromatic Compounds

The trifluoromethylthio group (SCF₃) is known as one of the electron-withdrawing groups and has attracted a lot of attention in recent years in the development of bioactive compounds, as it contributes to enhanced membrane permeability and lipophilicity.¹⁾ Conventional trifluoromethylthiolating reagents have mainly consisted of unstable compounds with high toxicity or corrosiveness, or highly hygroscopic metal-based reagents, leaving challenges in terms of handling and stability. MTTP is an air-stable and user-friendly trifluoromethylthiolating reagent that has been developed in recent years.²⁾ MTTP is an electrophilic reagent similar to TTST,³⁾ which exhibits versatile reactivity as an electrophile, nucleophile and radical source. Its most notable feature is its higher reactivity compared with TTST. For example, while the trifluoromethylthiolation of electron-deficient aromatic rings deactivated by substituents such as trifluoromethyl or ester groups is difficult with TTST, MTTP exhibits significantly higher reactivity even toward such substrates. In addition, MTTP is applicable to heterocycles including uracil derivatives, making it valuable for drug discovery research. Furthermore, MTTP can also be used for the trifluoromethylthiolation of active methylene compounds. Although this type of reactions typically proceed under basic conditions, MTTP enables the reaction to proceed under acidic conditions. As a result, MTTP can be broadly applied to base-sensitive compounds and is expected to serve as a valuable tool in drug discovery research.

Related Products

M3936

1-Methyl-4-[(trifluoromethyl)thio]piperazine (= MTTP)

T4211

S-(Trifluoromethyl) Trifluoromethanesulfonothioate (= TTST)

T0751

Trifluoromethanesulfonic Acid (= TfOH)

Related Product Category Pages

• Fluorination Reagents [Synthetic Reagents]

References

• 1) Synthetic Methods for Compounds Having CF₃–S Units on Carbon by Trifluoromethylation, Trifluoromethylthiolation, Triflylation, and Related Reactions
  • X. Xu, K. Matsuzaki, N. Shibata, Chem. Rev. 2014, 115, 731.
• 2) Synthesis and Electrophilic Trifluoromethylthiolation Properties of 1-Methyl-4-(trifluoromethylthio)piperazine (MTTP)
  • S. Miraghaee, T. Umemoto, G. B. Hammond, Org. Lett. 2024, 26, 6459.
• 3) Preparation and Reactivity Study of a Versatile Trifluoromethylthiolating Agent: S-Trifluoromethyl Trifluoromethanesulfonothioate (TTST)
  • Y. Yang, S. Miraghaee, R. Pace, T. Umemoto, G. B. Hammond, Angew. Chem. Int. Ed. 2023, 62, e202306095.

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