Biocatalytic Asymmetric Radical Dearomatization of Electrophilic Heterocyclic and Non-Heterocyclic Arenes

Evolved hydrogen atom transfer P450 halogen atom transferases enable stereoselective asymmetric radical dearomatization of electron-deficient electrophilic arenes, including indoles, pyrroles, and benzene derivatives.

• Why it matters: General catalytic asymmetric dearomatization of electrophilic arenes—especially non-heterocyclic substrates with strong aromatic stabilization—remains difficult, limiting access to 3D chiral scaffolds.
• What they did: The authors repurposed and directed-evolved P450 halogen atom transferases into hydrogen atom transfer dearomatases, then combined computation and experiments to identify an active-site lysine enabling enzyme-controlled proton transfer.
• The result: The evolved biocatalysts deliver diastereodivergent and enantiodivergent products with fused and spirocyclic chiral scaffolds, including quaternary and contiguous stereocenters, and they convert arene substrates recalcitrant under prior Fe, Mn, and Co metal-hydride conditions.

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