Decarboxylative formation of di- and trifluoromethyl groups with nucleophilic fluoride using an electron-deficient manganese porphyrin

Abstract

Di- and trifluoromethyl groups (CF2H and CF3) are often found in the medicinal chemistry and other fields for their modifications of biological properties, but are challenging to synthesize due to the lack of natural fluorination pathways. Furthermore, late stage fluorination methods are of particular interest for their applications in medical imaging radiotracers. Decarboxylative fluorination, using carboxylic acids, is a unique method to selectively install fluorine atoms among numerous fluorination strategies. Here, the bio-inspired catalyst manganese 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin Mn(TPFPP)Cl is reported for decarboxylative fluorination: this electron-deficient manganese porphyrin could expand beyond the scope and previous success of manganese tetramesitylporphyrin Mn(TMP)Cl in late stage fluoromethyl reactions. The condition optimization determined the effects of reaction time, manganese ligation, catalyst loading, oxidant loading, fluorine source loading, solvent, and pH on the reaction system. This decarboxylative fluorination catalyzed by Mn(TPFPP)Cl uses nucleophilic fluoride and has an expanded substrate scope for creating di- and trifluoromethyl substituents on a variety of aromatic rings, including those with electron-withdrawing groups, heteroatomic rings, esters, and complex, drug-like compounds.