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Die Ir‐katalysierte Borylierung aromatischer C‐H‐Bindungen ist heute die bevorzugte Methode zur Synthese aromatischer Organoborverbindungen. Sie ist hocheffizient, toleriert vielzählige Substituenten und kann bei carbo‐ wie auch heterocyclischen Substraten angewendet werden. Die Regioselektivität der C‐H‐Aktivierung beruht hauptsächlich auf sterischen Überlegungen, und in den letzten Jahren gab es erhebliche Bemühungen, selektivere Prozesse für weniger eingeschränkte Substrate zu entwickeln. Allerdings haben sich viele Arbeiten auf benzoide Arene konzentriert, wogegen Heteroarene begehrte und anspruchsvolle Substrate bleiben, in denen die Reaktivität und Regioselektivität von der Stellung und/oder Art der Heteroatome abhängt. Dieser Aufsatz gibt einen Überblick über die Borylierung von Heteroarenen und konzentriert sich auf den Einfluss sterischer und elektronischer Effekte auf das regiochemische Ergebnis. Außerdem soll er durch Verknüpfung mit dem derzeitigen mechanistischen Verständnis einen Einblick in die momentanen Möglichkeiten und Richtungen für weitere notwendige Entwicklungen bieten. [ABSTRACT FROM AUTHOR]

This report describes the development of a Zn(OTf)2‐mediated method for converting α‐tertiary haloamides to the corresponding fluorine‐18 labelled α‐tertiary fluoroamides with no‐carrier‐added [18F]tetramethylammonium fluoride. 1,5,7‐Triazabicyclo[4.4.0]dec‐5‐ene is an essential additive for achieving high radiochemical conversion. Under the optimised conditions, radiofluorination proceeds at sterically hindered tertiary sites in high radiochemical conversions, yields, and purities. This method has been successfully automated and applied to access >200 mCi (>7.4 GBq) of several model radiofluorides. Mechanistic studies led to the development of a new, nucleophilic C−H radiofluorination process using N‐sulphonyloxyamide substrates. [ABSTRACT FROM AUTHOR]

Natural d‐DNA and l‐DNA are mirror‐image counterparts. However, because of the inherent flexibility and conformation diversity of DNA, it is still not clear how enantiomeric compounds recognize d‐DNA and l‐DNA. Herein, taking G‐quadruplex (G4) DNA as an example that has diverse conformations and distinct biofunctions, the binding of ten pairs of iron triplex metallohelices to d‐ and l‐G4 DNA were evaluated. The Δ‐enantiomer binds to d‐DNA and the Λ‐enantiomer binds to l‐DNA, exhibiting almost the same stabilization effect and binding affinity. The binding affinity of the Δ‐metallohelix with d‐G4 is nearly 70‐fold higher than that of Λ‐metallohelix binding d‐G4. Δ‐Metallohelix binding to d‐G4 follows a two‐step binding process driven by a favorable enthalpy contribution to compensate for the associated unfavorable entropy. [ABSTRACT FROM AUTHOR]

Monosaccharides are added to the hydrophilic face of a self‐assembled asymmetric FeII metallohelix, using CuAAC chemistry. The sixteen resulting architectures are water‐stable and optically pure, and exhibit improved antiproliferative selectivity against colon cancer cells (HCT116 p53+/+) with respect to the non‐cancerous ARPE‐19 cell line. While the most selective compound is a glucose‐appended enantiomer, its cellular entry is not mainly glucose transporter‐mediated. Glucose conjugation nevertheless increases nuclear delivery ca 2.5‐fold, and a non‐destructive interaction with DNA is indicated. Addition of the glucose units affects the binding orientation of the metallohelix to naked DNA, but does not substantially alter the overall affinity. In a mouse model, the glucose conjugated compound was far better tolerated, and tumour growth delays for the parent compound (2.6 d) were improved to 4.3 d; performance as good as cisplatin but with the advantage of no weight loss in the subjects. [ABSTRACT FROM AUTHOR]

A transition‐metal‐free reductive hydroxymethylation reaction has been developed, enabling the preparation of tetrahydroisoquinolines bearing C4‐quaternary centers from the corresponding isoquinolines. Deuterium labelling studies and control experiments enable a potential mechanism to be elucidated which features a key Cannizzaro‐type reduction followed by an Evans–Tishchenko reaction. When isoquinolines featuring a proton at the 4‐position are used, a tandem methylation‐hydroxymethylation occurs, leading to the formation of 2 new C−C bonds in one pot. [ABSTRACT FROM AUTHOR]

A Cu‐mediated ortho‐C−H radiofluorination of aromatic carboxylic acids that are protected as 8‐aminoquinoline benzamides is described. The method uses K18F and is compatible with a wide range of functional groups. The reaction is showcased in the high specific activity automated synthesis of the RARβ2 agonist [18F]AC261066. [ABSTRACT FROM AUTHOR]