Photocatalytic Direct Deoxytrifluoromethoxylation of Phenols

Overview

This work presents a photoredox-catalyzed method for the deoxytrifluoromethoxylation of phenols, a transformation that removes the phenolic hydroxyl group. The strategy exploits the reactivity of the trifluoromethoxide anion, which decomposes to difluorophosgene under the reaction conditions. The generated difluorophosgene reacts in situ with the phenol substrate to form an aryl carbonofluoridate intermediate. This intermediate formation weakens the aryl carbon-oxygen bond, facilitating its subsequent cleavage. The approach addresses challenges in deoxygenating phenolic substrates by activating the typically strong Csp2-O bond through this intermediate transformation.

Methods and approach

The methodology employs organic photoredox catalysts to enable the transformation under mild conditions. The key mechanistic step involves the decomposition of the trifluoromethoxide anion into difluorophosgene, which acts as an activating reagent for the phenolic oxygen. The in situ formation of the aryl carbonofluoridate intermediate reduces the bond dissociation energy of the Csp2-O bond, rendering it susceptible to photoredox-mediated cleavage. The use of organic photocatalysts rather than transition metal complexes simplifies the reaction protocol and broadens its practical applicability.

Results

The method demonstrates broad substrate scope across various phenolic substrates while maintaining operational simplicity. The transformation exhibits high selectivity when multiple carbon-oxygen bonds are present in the substrate, selectively targeting the phenolic position for deoxygenation. The mild reaction conditions and photoredox activation enable successful conversion of structurally diverse phenols through the aryl carbonofluoridate intermediate pathway.

Implications

This photoredox strategy provides a new approach for phenol deoxygenation through activation of the Csp2-O bond via aryl carbonofluoridate formation. The method's selectivity in distinguishing the phenolic C-O bond from other oxygen-containing functionalities expands the synthetic toolkit for deoxygenative transformations of aromatic compounds. The reliance on organic photocatalysts and mild conditions may facilitate adoption in synthetic applications where traditional deoxygenation methods face limitations.