C―H functionalization strategies for the construction of thioethers

Thioesters, which are essential sulfur-containing organic molecules, are indispensable in natural products, pharmaceuticals, and organic light-emitting materials. Efficient synthesis of thioethers has received considerable attention due to the widespread applications of these compounds, and many fundamental approaches for C―S bond formation have been proposed. However, most of them construct C―S bonds by employing organic halides/organic boronic acid. These methodologies generally suffer from a pre-functionalized starting material. Recently, selective C―H functionalization emerged as a powerful tool for the synthesis of C―N, C―O, C―C, and C―halogen bonds. Nevertheless, C―S bond formation via C―H functionalization has only recently been given more importance because organosulfur compounds are believed to inactivate catalysts. In contrast to traditional crosscoupling reactions, direct functionalization of C―H bonds for the synthesis of thioethers can shorten the reaction steps and minimize the amount of waste formed. In this review, which is divided into several parts, we describe C―H functionalization strategies for the construction of thioethers. In Part I, we introduce the importance and widespread applications of thioethers in daily life. For example, Lissoclibadin 6 is a polysulfur aromatic alkaloid that shows antimicrobial activity. Seroquel is an antipsychotic medicine. It is used to treat bipolar disorder and schizophrenia in adults, and children who are at least 10 years old. Tazarotene is approved for the treatment of psoriasis, acne, and sun-damaged skin. Furthermore, a comparison between conventional synthesis methods and C―H thiolation is discussed. In Part II, we introduce copper-catalyzed or copper-mediated C―H thiolation. Along with the direct functionalization of sp2 and sp C―H for the synthesis of aryl sulfides, some significant and challenging thiolations of sp3 C―H are included. In addition to copper, palladium is an excellent catalyst for C―H functionalization. In Part III, we elucidate palladium-catalyzed C―H thiolation and discuss many proposed mechanisms. Nickel, which is a first-flow, low-cost, and earth-abundant metal catalyst, has increasingly gained attention. In contrast to copper and palladium, despite its late start, several remarkable reports on nickel-catalyzed C―H thiolation were published by several groups. Rhodium plays a key role in selective C―H functionalization. Some published results proved the capacity of rhodium catalysts to promote C―S construction via C―H functionalization. In Part IV, we introduce rhodium-catalyzed C―H thiolation. In recent years, metal-free C―H functionalization has been quite attractive. In Part V, some C―S construction strategies via metal-free C―H functionalization are presented. In the last part, the conclusion discusses the limitations and possible development directions of these advances in the construction of thioethers.