Christian Matheis

Sandmeyer Difluoromethylation of (Hetero-)Arenediazonium Salts

A Sandmeyer-type difluoromethylation process has been developed that allows the straightforward conversion of (hetero-)arenediazonium salts into the corresponding difluoromethyl (hetero-)arenes under mild conditions. The actual difluoromethylating reagent, a difluoromethyl-copper complex, is formed in situ from copper thiocyanate and TMS-CF2H. The diazonium salts are either preformed or generated in situ from broadly available aromatic amines.

Sandmeyer‐Type Trifluoromethylthiolation and Trifluoromethylselenolation of (Hetero)Aromatic Amines Catalyzed by Copper

Aromatic and heteroaromatic diazonium salts were efficiently converted into the corresponding trifluoromethylthio- or selenoethers by reaction with Me4 NSCF3 or Me4 NSeCF3 , respectively, in the presence of catalytic amounts of copper thiocyanate. These Sandmeyer-type reactions proceed within one hour at room temperature, are applicable to a wide range of functionalized molecules, and can optionally be combined with the diazotizations into one-pot protocols.

Copper‐Catalyzed Dehydrogenative Coupling of Arenes with Alcohols

Copper-Catalyzed Dehydrogenative Coupling of Arenes with Alcohols What a couple! Arenes functionalized with donating groups undergo oxidative dehydrogenative coupling with alcohols in the presence of a copper/silver catalyst system. This intermolecular C H alkoxylation provides a convenient synthetic route to the important class of aryl ethers. The catalyst system also allows the alkoxylation of benzylic C H groups with formation of benzyl alkyl ethers. Angewandte Chemie

Synthesis of Aryl Tri‐ and Difluoromethyl Thioethers via a CH‐Thiocyanation/Fluoroalkylation Cascade

An AlCl3 -catalyzed CH thiocyanation was discovered and combined with a Langlois-type trifluoromethylation to afford aryl trifluoromethyl thioethers directly from arenes, N-thiocyanatosuccinimide (NTS) and Ruppert-Prakash reagent. An analogous combination with a copper-mediated difluoromethylation gives access to aryl difluoromethyl thioethers. Both processes proceed with exceptional regioselectivity for the most electron-rich, sterically least hindered position of the arene. The sulfur and fluoroalkyl groups originate from different sources, so that the use of expensive, preformed fluoroalkylthiolation reagents is avoided.

Trifluoromethylthiolation and Trifluoromethylselenolation of α-Diazo Esters Catalyzed by Copper.

α-Diazo esters are smoothly converted into the corresponding trifluoromethyl thio- or selenoethers by reaction with Me4 NSCF3 or Me4 NSeCF3 , respectively, in the presence of catalytic amounts of copper thiocyanate. This straightforward method gives high yields under neutral conditions at room temperature and is applicable to a wide range of functionalized molecules, including diverse α-amino acid derivatives. It is well-suited for the late-stage introduction of trifluoromethylthio or -seleno groups into drug-like molecules.

Convenient synthesis of pentafluoroethyl thioethers via catalytic Sandmeyer reaction with a stable fluoroalkylthiolation reagent

Aromatic and heteroaromatic diazonium salts were smoothly converted into the corresponding pentafluoroethyl thioethers by reaction with Me4NSC2F5 in the presence of catalytic amounts of elemental copper. This Sandmeyer-type reaction proceeds at room temperature under mild conditions and is applicable to a wide range of functionalised molecules. It enables the late-stage introduction of pentafluoroethylthio groups, a promising but largely unexplored substituent, into bioactive molecules.