Abstract
Direct trifluoromethylation of unactivated aromatic rings at metabolically susceptible positions is highly desirable in pharmaceutical applications. By incorporating thiophenes into the backbone of triphenylamine to enlarge its π-system, a new approach for constructing coordination polymers is reported for direct trifluoromethylation without prefunctionalization of the aryl precursors. The improved light-harvesting ability and well-modulated excited state redox potential of the designed polymers endow the generated CF3 radicals with suitable reactivity and enhance radical adduct oxidation in pores. The well-configurated interactions between the organic ligands distort the coordination geometry to create active interaction sites within the coordination polymer; thus, the substrates could be docked near the photoredox-active centres. The synergistic electronic and spatial effects in the confined pores balance the contradictory demands of electronic effects and reaction dynamics, achieving regio- and diastereoselective discrimination among reaction sites with unremarkable electronic/steric differences.
Highlights
Direct trifluoromethylation of unactivated aromatic rings at metabolically susceptible positions is highly desirable in pharmaceutical applications
Appending trifluoromethyl groups to the metabolically susceptible positions of aromatics without prefunctionalization of precursors[7] is highly desirable, and it is promising to achieve this goal by merging all the catalytic requirements to controllably generate CF3 radicals under visible light and trigger the metabolically susceptible positions of aromatic drug candidates
As the integration of near-ultraviolet (UV) responsive triphenylamine (TPA) and covalently binding group L-proline derivative into a single coordination polymer has been proven to be an effective approach to the photocatalytic α-15 or β-functionalization[16] of saturated carbonyl compounds, we believe that merging the TPAbased chromophore with modulated photoelectronic property and the noncovalently binding site together within one framework is a potential strategy for controllably generating CF3 radicals under visible-light irradiation and harnessing the aromatic drug candidates that lack of covalent binding moieties
Summary
Direct trifluoromethylation of unactivated aromatic rings at metabolically susceptible positions is highly desirable in pharmaceutical applications. In light of the photoinduced generation of highly reactive CF3 radicals, polypyridyl noble metal complexes enable direct C–H trifluoromethylation of unactivated aromatics under visible-light irradiation[4] This approach bypasses tedious prefunctionalization of aryl precursors that is needed for transition metal-catalysed cross-couplings using a nucleophilic or electrophilic source of CF35,6. As the integration of near-ultraviolet (UV) responsive triphenylamine (TPA) and covalently binding group L-proline derivative into a single coordination polymer has been proven to be an effective approach to the photocatalytic α-15 or β-functionalization[16] of saturated carbonyl compounds, we believe that merging the TPAbased chromophore with modulated photoelectronic property and the noncovalently binding site together within one framework is a potential strategy for controllably generating CF3 radicals under visible-light irradiation and harnessing the aromatic drug candidates that lack of covalent binding moieties. The intrinsic crystalline nature of coordination polymers allows for structural analyses of the intermediates formed in each activation and catalytic step, offering an excellent platform for studying photon capture, electron delivery, and catalytic activation[17,18]
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