3,3-Dimethyl-1-(trifluoromethyl)-1,2-benziodoxole (Togni Reagent)

The direct transfer of a trifluoromethyl group usually requires harsh conditions that are often incompatible with more sensitive functionalities in a molecule. Nucleophilic trifluoromethylation is the most common method, due in large part to the broad applicability of the Ruppert–Prakash reagent (Me3SiCF3). Most reagents for electrophilic C- and S-trifluoromethylation are considerably less developed. Antonio Togni and coworkers have recently reported a new electrophilic reagent based on hypervalent iodine, 3,3-dimethyl- 1-(trifluoromethyl)-1,2-benziodoxole,1 which nicely complements the nucleophilic Ruppert–Prakash reagent.

The Togni reagent is easy to handle, and can be exposed to moist air for short periods of time without any apparent alteration. β-Ketoesters were found to react with the Togni reagent under phase-transfer catalysis conditions to yield the α-trifluoromethylated derivatives (Scheme 1). More interesting are the trifluoromethylations of α-nitroesters, which yield precursors to α-trifluoromethyl-α-amino acids (Scheme 2).

Scheme 1

Scheme 2

Aromatic and aliphatic thiols undergo selective S-trifluoromethylation in the presence of the Togni reagent, without formation of the corresponding disulfide (Scheme 3). The reaction is remarkably tolerant of various functional groups and does not show significant solvent dependence, allowing for the use of the Togni reagent at the latter stages of syntheses of complex molecules.

Scheme 3

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  1. (a) Eisenberger, P. et al. Chem.-Eur. J. 2006, 12, 2579. (b) Kieltsch, I. et al. Angew. Chem. Int. Ed. 2007, 46, 754.

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