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The reduction of oximes was recently identified as a promiscuous activity of Old Yellow Enzymes (OYEs). This reaction involves a two‐step reduction of α‐oxime‐ß‐ketoesters to the corresponding amines, which spontaneously dimerise to yield pyrazine derivatives. This biotransformation is currently limited to substrates with small substituents like methyl/ethyl on the keto moiety. We used a structure‐based approach to engineer 12‐oxophytodienoate reductase 3 (OPR3) from Solanum lycopersicum as a prototypical OYE to accept oximes with bulkier substituents. To this end, three single and two double variants were prepared and tested on six oxime substrates. The engineered variants indeed showed activity on some of the bulkier substrates, which had not been converted at all by the wild‐type enzyme, including the diester compound diethyl‐2‐(hydroximino) malonate. While we were unable to identify variants capable of converting substrates with branched and aromatic substituents, the results demonstrate the validity of our engineering approach, suggesting potential pathways for expanding the substrate scope of OYEs. [ABSTRACT FROM AUTHOR]

We have utilized a C–H homocoupling defect that plagues direct heteroarylation polymerization reactions to access a molecular dimer based on diketopyrrolopyrrole and perylene diimide. This synthetic route, which also incorporates a direct heteroarylation mono-substitution, proved to be an effective method to access this class of compound. The dimer, PDI-DPP-DPP-PDI, presented an overall electron-deficient π-conjugated molecular framework with strong optical absorption from 400–800 nm. The low energy absorption from 600–800 nm is a feature not accessible by the monomeric analogue, highlighting the potential of this dimerization method to be used for spectral engineering of π-conjugated materials. [ABSTRACT FROM AUTHOR]

Cobalt-porphyrin-catalysed intramolecular ring-closing C−H bond amination enables direct synthesis of various N-heterocycles from aliphatic azides. Pyrrolidines, oxazolidines, imidazolidines, isoindolines and tetrahydroisoquinoline can be obtained in good to excellent yields in a single reaction step with an air- and moisture-stable catalyst. Kinetic studies of the reaction in combination with DFT calculations reveal a metallo-radical-type mechanism involving rate-limiting azide activation to form the key cobalt(III)-nitrene radical intermediate. A subsequent low barrier intramolecular hydrogen-atom transfer from a benzylic C−H bond to the nitrene-radical intermediate followed by a radical rebound step leads to formation of the desired N-heterocyclic ring products. Kinetic isotope competition experiments are in agreement with a radical-type C−H bond-activation step (intramolecular KIE=7), which occurs after the rate-limiting azide activation step. The use of di- tert-butyldicarbonate (Boc2O) significantly enhances the reaction rate by preventing competitive binding of the formed amine product. Under these conditions, the reaction shows clean first-order kinetics in both the [catalyst] and the [azide substrate], and is zero-order in [Boc2O]. Modest enantioselectivities (29-46 % ee in the temperature range of 100-80 °C) could be achieved in the ring closure of (4-azidobutyl)benzene using a new chiral cobalt-porphyrin catalyst equipped with four (1 S)-(−)-camphanic-ester groups. [ABSTRACT FROM AUTHOR]

A snake bites its own tail in the cobalt‐catalysed activation of aliphatic azides, enabling the direct synthesis of several N‐heterocycles from aliphatic azides in good to excellent yields. Detailed mechanistic investigations revealed a metallo‐radical intramolecular C−H activation mechanism, and enantioselective radical‐type ring‐closure C−H amination from aliphatic azides proved possible. More information can be found in the Full Paper by B. de Bruin et al. on page 7945. [ABSTRACT FROM AUTHOR]