Mechanistic Investigation of Oxidative Decarboxylation Catalyzed by Two Iron(II)- and 2‑Oxoglutarate-Dependent Enzymes

Two non-heme iron enzymes, IsnB and AmbI3, catalyze a novel decarboxylation-assisted olefination to produce indole vinyl isonitrile, an important building block for many natural products. Compared to other reactions catalyzed by this enzyme family, decarboxylation-assisted olefination represents an attractive biosynthetic route and a mechanistically unexplored pathway in constructing a CC bond. Using mechanistic probes, transient state kinetics, reactive intermediate trapping, spectroscopic characterizations, and product analysis, we propose that both IsnB and AmbI3 initiate stereoselective olefination via a benzylic C–H bond activation by an Fe­(IV)–oxo intermediate, and the reaction likely proceeds through a radical- or carbocation-induced decarboxylation to complete CC bond installation.