Enantioselective C−H Activation with Earth‐Abundant 3d Transition Metals

Molecular syntheses largely rely on time‐ and labour‐intensive prefunctionalization strategies. In contrast, C?H activation represents an increasingly powerful approach that avoids lengthy syntheses of prefunctionalized substrates, with great potential for drug discovery, the pharmaceutical industry, material sciences, and crop protection, among others. The enantioselective functionalization of omnipresent C?H bonds has emerged as a transformative tool for the step‐ and atom‐economical generation of chiral molecular complexity. However, this rapidly growing research area remains dominated by noble transition metals, prominently featuring toxic palladium, iridium and rhodium catalysts. Indeed, despite significant achievements, the use of inexpensive and sustainable 3d metals in asymmetric C?H activations is still clearly in its infancy. Herein, we discuss the remarkable recent progress in enantioselective transformations via organometallic C?H activation by 3d base metals up to April 2019.     

Unusual Bonding and Properties in Main Group Element Chemistry: Rational Synthesis,Characterization, and Experimental Electron Density Determination of Mixed‐Valent Tetraphosphetes

Five dispirocyclic λ³,λ⁵‐tetraphosphetes [{R₂Si(NR¹)(NR²)P₂}₂] (R¹ = R² and R¹ ≠ R²) are easily prepared in almost quantitative yields via photolysis of the respective bis(trimethylsilyl)phosphanyldiazaphosphasiletidines with intense visible light. These deep‐yellow low‐coordinate phosphorus compounds can be considered as the first higher congeners of the well‐known cyclodiphosphazenes. The tetraphosphetes are remarkably stable in air and show unexpected molecular properties related to the unique bonding situation of the central four‐π‐electron four‐membered phosphorus ring. The extent of rhombic distortion of the central P₄ ring is remarkable due to an unusually acute angle at the σ²‐phosphorus atoms. All of the P?P bonds are approximately equal in length. The distances are in the middle of the range given by phosphorus single and double bonds. The anisotropic absorption of visible light that can easily be observed in the case of the yellow/colorless dichroic crystals of [{Me₂Si(NtBu)(NtBu)P₂}₂] and the exceptional ³¹P NMR chemical shift of the σ²‐phosphorus atoms are the most remarkable features of the λ³,λ⁵‐tetraphosphetes. In the case of [{Me₂Si(NtBu)(NtBu)P₂}₂], the Hansen–Coppens multipole model is applied to extract the electron density from high‐resolution X‐ray diffraction data obtained at 100 K. Static deformation density and topological analysis reveal a unique bonding situation in the central unsaturated P₄ fragment characterized by polar σ‐bonding, pronounced out‐of‐ring non‐bonding lone pair density on the σ²‐phosphorus atoms, and an additional non‐classical three‐center back‐bonding contribution.     

Directing-Group-Free C7-Alkylations of N-Alkylindoles Mediated by Cationic Zirconium Complexes: Role of Brønsted Acid for Catalytic Manifold

Highly position selective alkylations of N-alkylindoles at C7-positions have been enabled by cationic zirconium complexes. The strategy provides a straightforward access to install alkyl groups at C7-positions of indoles without a complex directing group. Mechanistic studies provided support for the importance of Brønsted acids in the catalytic manifold.     

Comprehensive Profiling by Non-targeted Stable Isotope Tracing Capillary Electrophoresis-Mass Spectrometry: A New Tool Complementing Metabolomic Analyses of Polar Metabolites

Mass spectrometry (MS) driven metabolomics is a frequently used tool in various areas of life sciences; however, the analysis of polar metabolites is less commonly included. In general, metabolomic analyses lead to the detection of the total amount of all covered metabolites. This is currently a major limitation with respect to metabolites showing high turnover rates, but no changes in their concentration. Such metabolites and pathways could be crucial metabolic nodes (e.g., potential drug targets in cancer metabolism). A stable-isotope tracing capillary electrophoresis–mass spectrometry (CE-MS) metabolomic approach was developed to cover both polar metabolites and isotopologues in a non-targeted way. An in-house developed software enables high throughput processing of complex multidimensional data. The practicability is demonstrated analyzing [U-¹³C]-glucose exposed prostate cancer and non-cancer cells. This CE-MS-driven analytical strategy complements polar metabolite profiles through isotopologue labeling patterns, thereby improving not only the metabolomic coverage, but also the understanding of metabolism.     

Change of evaporation rate of single monocomponent droplet with temperature using time-resolved phase rainbow refractometry

Droplet evaporation characterization, although of great significance, is still challenging. The recently developed phase rainbow refractometry (PRR) is proposed as an approach to measuring the droplet temperature, size as well as evaporation rate simultaneously, and is applied to a single flowing n-heptane droplet produced by a droplet-on-demand generator. The changes of droplet temperature and evaporation rate after a transient spark heating are reflected in the time-resolved PRR image. Results show that droplet evaporation rate increases with temperature, from ?1.28$\times {10}^{?8}$ m²/s at atmospheric 293 K to a range of (?1.5, ?8)$\times {10}^{?8}$ m²/s when heated to (294, 315) K, agreeing well with the Maxwell and Stefan–Fuchs model predictions. Uncertainty analysis suggests that the main source is the indeterminate gradient inside droplet, resulting in an underestimation of droplet temperature and evaporation rate. With the demonstration on simultaneous measurements of droplet refractive index as well as droplet transient and local evaporation rate in this work, PRR is a promising tool to investigate single droplet evaporation in real engine conditions.     

Electrophotocatalytic Undirected C−H Trifluoromethylations of (Het)Arenes

Electrophotochemistry has enabled arene C−H trifluoromethylation with the Langlois reagent CF₃SO₂Na under mild reaction conditions. The merger of electrosynthesis and photoredox catalysis provided a chemical oxidant-free approach for the generation of the CF₃ radical. The electrophotochemistry was carried out in an operationally simple manner, setting the stage for challenging C−H trifluoromethylations of unactivated arenes and heteroarenes. The robust nature of the electrophotochemical manifold was reflected by a wide scope, including electron-rich and electron-deficient benzenes, as well as naturally occurring heteroarenes. Electrophotochemical C−H trifluoromethylation was further achieved in flow with a modular electro-flow-cell equipped with an in-operando monitoring unit for on-line flow-NMR spectroscopy, providing support for the single electron transfer processes.