By using structure-guided directed evolution, the substrate scope of the FeII and α-ketoglutarate dependent halogenase Wi-WelO15 from Westiella intricata HT-29-1 was engineered to enable chemo-, regio-, and diastereoselective chlorination of unactivated C­(sp3)–H bonds using NaCl as chlorine source. While FeII dependent enzymes are often oxygen sensitive, variants of this halogenase could be screened in lysates under aerobic conditions. The developed biocatalysts offer a route to mild, late-stage chlorination on milligram scale of non-natural hapalindoles containing a ketone instead of an isonitrile functionality, thereby unlocking them for preparative biocatalysis.

An electrochemical access to iodinated aromatic compounds starting from trimethylsilyl-substituted arenes is presented. By design of experiments, highly efficient and mild conditions were identified for a wide range of substrates. A functional group stability test and the synthesis of an important 3-iodobenzylguanidine radiotracer illustrate the scope of this process.

The application of Lewis acidic chiral-atmetal complexes of iridium(III) and rhodium(III) as catalysts for the asymmetric polarized Nazarov cyclization of dihydropyran-and indole-functionalized a-unsaturated b-ketoesters is reported (overall 24 examples). For both substrate classes, catalyst loadings of 2 mol% were found to be sufficient for achieving high yields and high stereoselectivities. The cyclized dihydropyran products were isolated in 85-98% yield, with 89%-> 99% ee, and trans/cis ratios of 15:1-50:1 (9 examples). The cyclized indole products were typically isolated in more than 70% yield and in up to 93% yield, typically with more than 90% ee and in up to 97% ee, and trans/cis ratios of 12:1-28:1 (15 examples).

Ein neuer elektrochemischer Zugang zu Iodaromaten ausgehend von Trimethylsilyl-substituierten Aromaten wird präsentiert. Durchs tatistische Versuchsplanung konnten sehr effiziente und milde Reaktionsbedingungen gefunden und auf eine Vielzahl von Substraten angewendet werden. Ein Kompatibilitätstest und die Verwendung der Methode zur Synthese eines 3-Iodbenzylguanidin-Derivats (Radiomarker) illustrieren die Anwendungsbreite.Schema 1. Iodierungsreaktionen. [5,6]