journal article

Journal Article

Text

Tetrahedron Letters. 2026, 176, p. 155957

Synthesis and chemical properties of electron-deficient porphyrin cofactors with trifluoromethyl groups

Elsevier Ltd

English

Text

2026-01-07

https://doi.org/10.1016/j.tetlet.2025.155957

Sonoda C., Hayashi T.. Synthesis and chemical properties of electron-deficient porphyrin cofactors with trifluoromethyl groups. Tetrahedron Letters 176, 155957 (2026); https://doi.org/10.1016/j.tetlet.2025.155957.

We report the synthesis and characterization of three new electron-deficient iron porphyrins bearing trifluoromethyl group substituents; FePormCF₃, FePorβMe₂(CF₃)₄ and FePorβEt₂(CF₃)₄. FePormCF₃, substituted with a CF₃ group at the meso -position, and FePorβMe₂(CF₃)₄, substituted with four CF₃ and two methyl groups at the pyrrole β-positions, were synthesized via coupling of two dipyrromethane molecules, while FePorβEt₂(CF₃)₄, where two methyl groups of FePorβMe₂(CF₃)₄ were replaced with ethyl groups, was obtained through a biladiene- ac precursor route involving copper-templated cyclization. The corresponding free-base porphyrins were characterized by NMR and mass spectrometry, revealing clear electronic effects caused by the CF₃ substituents. The ¹H and ¹⁹F NMR spectra indicate downfield shifts of inner NHs, suggesting that the electron-withdrawing CF₃ groups decrease the electron density of the porphyrin π-system and weaken the aromatic ring current. Differential pulse voltammetry measurements demonstrated positive shifts of the Fe(II)/Fe(III) redox potentials to −715 mV and −355 mV vs. Fc/Fc+ for FePormCF₃ and FePorβMe₂(CF₃)₄, respectively, confirming that introduction of the CF₃ substituents effectively stabilizes the ferrous state. These results highlight how CF₃ substitution modulates the electronic structure and redox properties of metalloporphyrins. In addition, it has been confirmed that these iron complexes can be incorporated into the myoglobin heme pocket. The present study establishes versatile synthetic approaches for introducing strong electron-withdrawing groups into heme analogues, in our efforts to develop useful attractive artificial cofactors with controlled redox potentials and unique reactivity.

103815

Synthesis and chemical properties of electron-deficient porphyrin cofactors with trifluoromethyl groups

Elsevier Ltd

English

2026-01-07

Tetrahedron Letters

176

155957

https://doi.org/10.1016/j.tetlet.2025.155957

https://hdl.handle.net/11094/103815