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Abstract: Isoxazolinones are biologically and synthetically interesting densely functionalized heterocycles, which for a long time were not accessible in enantioenriched form by asymmetric catalysis. Next to the deficit of enantioselective methods, the functionalization of isoxazolinones is often plagued by regioselectivity issues due to the competition of various nucleophilic centers within the heterocycles. We report the first regio‐ and enantioselective C‐allylations of isoxazolinones. These occur with high regioselectivity in favor of the linear allylation products, although Ir phosphoramidite catalysts were used, which commonly results in branched isomers. Our studies suggest that this outcome is the result of a reaction cascade via an initial regio‐ and enantioselective N‐allylation to provide a branched allyl intermediate, followed by a spontaneous [3,3]‐rearrangement resulting in chirality transfer. [ABSTRACT FROM AUTHOR]

Salicylate 1,2-dioxygenase (SDO) is the first enzyme to be discovered to catalyze the oxidative cleavage of a monohydroxylated aromatic compound, namely salicylate, instead of the well-known electron-rich substrates. We have investigated the mechanism of dioxygen activation in SDO by QM/MM calculations. Our study reveals that the non-heme FeII center in SDO activates salicylate and O2 synergistically through a strong covalent interaction to facilitate the reductive cleavage of O2. A covalent salicylate-FeII-O2 complex is the reactive oxygen species in this case, and its electronic structure is best described as being between the two limiting cases, FeII−O2 and FeII−O2.−, with partial electron transfer from the activated salicylate to O2 via the Fe center. Thus SDO employs a synergistic strategy of substrate and oxygen activation to carry out the catalytic reaction, which is unprecedented in the family of iron dioxygenases. Moreover, O2 activation in SDO happens without the assistance of a proton source. Our study essentially shows a new mechanistic possibility for O2 activation. [ABSTRACT FROM AUTHOR]