Late-stage Derivatization of Buflavine by Nickel-catalyzed Direct Substitution of a Methoxy Group via C-O Bond Activation

The nickel-catalyzed cross-coupling of methoxyarenes was applied to buflavine, which allows for the selective monosubstitution of one of the two methoxy groups in the molecule, leading to the formation of 2- and 3-substituted isomers. Trimethylsilylmethyl (TMSCH2), phenyl, and alkynyl groups can be introduced into buflavine using this method. The resulting TMSCH2 analogue of buflavine can also be converted into several other derivatives.