Pathway from N-Alkylglycine to Alkylisonitrile Catalyzed by Iron(II) and 2-Oxoglutarate-Dependent Oxygenases

N-alkylisonitrile, a precursor to isonitrile-containing lipopeptides, is biosynthesized by decarboxylation-assisted -N≡C group (isonitrile) formation by using N-alkylglycine as the substrate. This reaction is catalyzed by iron(II) and 2-oxoglutarate (Fe/2OG) dependent enzymes. Distinct from typical oxygenation or halogenation reactions catalyzed by this class of enzymes, installation of the isonitrile group represents a novel reaction type for Fe/2OG enzymes that involves a four-electron oxidative process. Reported here is a plausible mechanism of three Fe/2OG enzymes, Sav607, ScoE and SfaA, which catalyze isonitrile formation. The X-ray structures of iron-loaded ScoE in complex with its substrate and the intermediate, along with biochemical and biophysical data reveal that -N≡C bond formation involves two cycles of Fe/2OG enzyme catalysis. The reaction starts with an Fe^IV-oxo-catalyzed hydroxylation. It is likely followed by decarboxylation-assisted desaturation to complete isonitrile installation.     

Decarboxylative ipso Amination of Activated Benzoic Acids

In the presence of a bimetallic Pd/Cu system with 1,10‐phenanthroline as the ligand and either air or N‐methylmorpholine N‐oxide as the oxidant, electron‐deficient benzoic acids undergo oxidative decarboxylative coupling with unprotected amines. This operationally simple aniline synthesis is widely applicable with respect to the amine and gives good yields, even on multigram scale. The orthogonality of this reaction to other Pd‐catalyzed cross‐couplings allows the concise synthesis of multisubstituted arenes by sequential C?C, C?Cl, and C?N functionalizations. Mechanistic investigations suggest the intermediacy of a hypervalent Pd species.     

Decarboxylative Alkynylation and Carbonylative Alkynylation of Carboxylic Acids Enabled by Visible‐Light Photoredox Catalysis

Visible‐light‐induced photocatalytic decarboxylative alkynylations of carboxylic acids have been developed for the first time. The reaction features extremely mild conditions, broad substrate scope, and avoids additional oxidants. Importantly, a decarboxylative carbonylative alkynylation has also been carried out in the presence of carbon monoxide (CO) under photocatalytic conditions, which affords valuable ynones in high yields at room temperature.