Enhancing Flavins Photochemical Activity in Hydrogen Atom Abstraction and Triplet Sensitization through Ring‐Contraction

The reaction of ester-modified flavins with hydroxide base leads to ring-contracted imidazolonequinoxalines with increased triplet energy ( E _T) and H-atom abstraction (HAT) strength in the photochemically excited state. Ring-contracted flavins are efficient catalysts in the trifluoromethylthiolation of aliphatic C−H positions and also in multi-step sequences, which require the combined activity as triplet sensitizer and hydrogen atom abstractor.

Abstract

The isoalloxazine heterocycle of flavin cofactors reacts with various nucleophiles to form covalent adducts with important functions in enzymes. Molecular flavin models allow for the characterization of such adducts and the study of their properties. A fascinating set of reactions occurs when flavins react with hydroxide base, which leads to imidazolonequinoxalines, ring-contracted flavins, with so far unexplored activity. We report a systematic study of the photophysical properties of this new chromophore by absorption and emission spectroscopy as well as cyclic voltammetry. Excited, ring-contracted flavins are significantly stronger hydrogen atom abstractors when compared to the parent flavins, which allowed the direct trifluoromethylthiolation of aliphatic methine positions (bond dissociation energy (BDE) of 400.8 kJ mol⁻¹). In an orthogonal activity, their increased triplet energy ( E (S₀←T₁)=244 kJ mol⁻¹) made sensitized reactions possible which exceeded the power of standard flavins. Combining both properties, ring-contracted flavin catalysts enabled the one-pot, five-step transformation of α-tropolone into trans-3,4-disubstituted cyclopentanones. We envision this new class of flavin-derived chromophores to open up new modes of reactivity that are currently impossible with unmodified flavins.

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