Deuteration of Arylthianthren-5-ium Salts in CD₃OD

Abstract

Deuteration of arylthianthren-5-ium triflates with CD 3 OD or CD 3 OD/CD 3 COCD 3 in the presence of Cs 2 CO 3 by palladium catalysis or photoirradiation allowed the convenient synthesis of deuterated arenes in good yields. The Pd-catalyzed reaction generally gave better yields than the photoinduced deuteration, but exceptions also exist. They could complement each other in some cases. These reactions featured eco-friendly conditions, simplicity, inexpensive deuterium sources, good functional group tolerance, and a range of substrates. Since arylthianthren-5-ium salts could be readily synthesized from arenes and thianthrene 5-oxide, this protocol provided a formal aromatic C−H deuteration with high selectivity, enabling efficient deuterium labeling of multifunctionalized arenes and drug molecules.

Regioselective Deuteration of Arenes Enabled by Simple Heterogeneous Palladium Catalysis

“…Based on the mechanistic experiments and previous literature reports, − we proposed a plausible mechanism, as depicted in Scheme . A reasonable palladium-catalytic pathway involving oxidative addition of palladium with aryl salts 1 , anion exchange of DCOONa onto the palladium center, sequential palladium-catalyzed decarboxylation of B , and final reductive elimination was responsible for the formation of desired deuterated products 2 .…”

“…Meanwhile, Ritter and coworkers reported a homogeneous palladium-catalyzed deuteration and tritiation of arenes utilizing D 2 gas and T 2 gas as the hydrogen isotope sources via a regioselective C­(sp 2 )–H thianthrenation (Scheme d) . Recently, Zhang also reported a sulfonium-mediated deuteration of arenes by the catalysis of palladium or visible light with the requirement of deuterated solvents …”

“…51 Recently, Zhang also reported a sulfonium-mediated deuteration of arenes by the catalysis of palladium or visible light with the requirement of deuterated solvents. 52 Although recent significant homogeneous palladium-catalytic platforms were well developed for various functionalizations of aryl thianthrenium salts, 53−56 many nonnegligible limitations involving high loading of the catalyst, worse performance in separation, and recyclability of the catalyst from the catalytic system would appear to suppress the practical application, especially for the large-scale industrial processes. With the development of sustainable chemistry, some heterogeneous palladium-catalyzed systems have already been developed.…”

Thianthrenation-Enabled Pyrrolidin-2-yl and Tetrahydrofuran-2-yl Methylation of (Hetero)Arenes

“…The generated arylthianthrenium (aryl-TT) salt is prepared with an extremely high site selectivity via a C–H functionalization of arenes with thianthrene ( S )-oxides (TTSO). This aryl-TT salt possesses high reactivity and is involved in a number of transition metal-catalyzed, photoirradiated, and other transformations . Herein, we report a thianthrenation-enabled pyrrolidin-2-yl and tetrahydrofuran-2-yl methylation of (hetero)­arenes and demonstrate the potential application in the late-stage functionalization of complex pharmaceuticals (Scheme c).…”

Photoinduced Catalyst-Free Deuterodefunctionalization of Aryltriazenes with CDCl3

“…For instance, lithium-halogen exchange, transition-metal-catalyzed deuteration, photoinduced deuteration, and electrochemical reductive deuteration have been reported (Scheme a). Besides, aryl diazonium salts and aryl thianthrenium salts as electrophilic aryl reagents (Scheme a) as well as arylboronic acids or esters, aryl aldehyde, and arylazosulfones as nucleophilic aryl reagents were also used to synthesize aromatic deuterated compounds (Scheme b). However, the previously established methods required the use of reactive alkyllithium reagents, transition metal catalysts, strong bases, photosensitizers, or expensive deuterium donors, which limit the scope of their applications.…”