A General and Scalable Synthesis of Aeruginosin Marine Natural Products Based on Two Strategic C(sp3)H Activation Reactions

An efficient and scalable access to the aeruginosin family of marine natural products, which exhibit potent inhibitory activity against serine proteases, is reported. This synthesis was enabled by the strategic use of two different, recently implemented C(sp³)? H activation reactions. The first method led to the common 2‐carboxy‐6‐hydroxyoctahydroindole (Choi) core of the target molecules on a large scale, whereas the second one provided rapid and divergent access to the various hydroxyphenyllactic (Hpla) subunits. This strategy allowed the synthesis of the aeruginosins 98B and 298A, with the latter being obtained in unprecedentedly large quantities.     

O2‐mediated dehydrogenative amination of phenols

A method was developed for the direct dehydrogenative construction of C? N bonds between unprotected phenols and a series of cyclic anilines without resorting to any kind of metal activation of either substrate and without the use of halides. The resulting process relies on the exclusively organic activation of molecular oxygen and the subsequent oxidation of the aniline substrate. This allows the coupling of ubiquitous phenols, thus furnishing aminophenols through an atom‐economical and most sustainable dehydrogenative amination method. This new reactivity, which relies on the intrinsic organic reactivity of cumene in what can be seen as a modified Hock activation process of oxygen, is expected to have a large impact on the formation of C? N bonds in organic synthesis.     

Multiscale Modeling of the Active Site of [Fe] Hydrogenase: The H2 Binding Site in Open and Closed Protein Conformations

A series of QM/MM optimizations of the full protein of [Fe] hydrogenase were performed. The FeGP cofactor has been optimized in the water‐bound resting state ( 1 ), with a side‐on bound dihydrogen ( 2 ), or as a hydride intermediate ( 3 ). For inclusion of H₄ MPT in the closed structure, advanced multiscale modeling appears to be necessary, especially to obtain reliable distances between CH‐H₄MPT⁺ and the dihydrogen (H₂) or hydride (H^?) ligand in the FeGP cofactor. Inclusion of the full protein is further important for the relative energies of the two intermediates 2 and 3 . We finally find that hydride transfer from 3 has a significantly higher barrier than found in previous studies neglecting the full protein environment.     

In Situ Generation of Difluoromethyl Diazomethane for [3+2] Cycloadditions with Alkynes

A novel approach to agrochemically important difluoromethyl‐substituted pyrazoles has been developed based on the elusive reagent CF₂HCHN₂, which was synthesized (generated in situ) for the first time and employed in [3+2] cycloaddition reactions with alkynes. The reaction is extremely practical as it is a one‐pot process, does not require a catalyst or the isolation of the potentially toxic and explosive gaseous intermediate, and proceeds in a common solvent, namely chloroform, in air. The reaction is also scalable and allows for the preparation of the target pyrazoles on gram scale.     

Isolation and Total Synthesis of Kirkamide,an Aminocyclitol from an Obligate Leaf Nodule Symbiont

The new C₇N aminocyclitol kirkamide ( 1 ) was isolated from leaf nodules of the plant Psychotria kirkii by using a genome‐driven ¹H NMR‐guided fractionation approach. The structure and absolute configuration were elucidated by HRMS, NMR, and single‐crystal X‐ray crystallography. An enantioselective total synthesis was developed, which delivered kirkamide ( 1 ) on a gram scale in 11 steps and features a Ferrier carbocyclization and a Pd‐mediated hydroxymethylation. We propose that kirkamide is synthesized by Candidatus Burkholderia kirkii, the obligate leaf symbiont of Psychotria kirkii. Kirkamide ( 1 ) was shown to be toxic to aquatic arthropods and insects, thus suggesting that bacterial secondary metabolites play a protective role in the Psychotria/Burkholderia leaf nodule symbiosis.     

Direct Imaging of Octahedral Distortion in a Complex Molybdenum Vanadium Mixed Oxide

Complex Mo,V‐based mixed oxides that crystallize in the orthorhombic M1‐type structure are promising candidates for the selective oxidation of small alkanes. The oxygen sublattice of such a complex oxide has been studied by annular bright field scanning transmission electron microscopy. The recorded micrographs directly display the local distortion in the metal oxygen octahedra. From the degree of distortion we are able to draw conclusions on the distribution of oxidation states in the cation columns at different sites. The results are supported by X‐ray diffraction and electron paramagnetic resonance measurements that provide integral details about the crystal structure and spin coupling, respectively.     

Frenkel‐Defect‐Mediated Chemical Ordering Transition in a Li–Mn–Ni Spinel Oxide

Using spinel‐type Li(Mn_1.5Ni_0.5)O₄ with two different cations, Mn and Ni, in the oxygen octahedra as a model system, we show that a cation ordering transition takes place through the formation of Frenkel‐type point defects. A series of experimental results based on atomic‐scale observations and in situ powder diffractions along with ab initio calculations consistently support such defect‐mediated transition behavior. In addition to providing a precise suggestion of the intermediate transient states and the resulting kinetic pathway during the transition between two phases, our findings emphasize the significant role of point defects in ordering transformation of complex oxides.