Late-Stage Diversification of Biologically Active Molecules via Chemoenzymatic C–H Functionalization

Engineered variants of rebeccamycin halogenase were used to selectively halogenate a number of biologically active aromatic compounds. Subsequent Pd-catalyzed cross-coupling reactions on the crude extracts of these reactions were used to install aryl, amine, and ether substituents at the halogenation site. This simple, chemoenzymatic method enables nondirected functionalization of C–H bonds on a range of substrates to provide access to derivatives that would be challenging or inefficient to prepare by other means.