Palladium-catalyzed C–S bond activation and functionalization of 3-sulfenylindoles and related electron-rich heteroarenes

Abstract

A novel palladium-catalyzed approach for constructing functionalized heteroarenes via C–S bond cleavage and C–C bond formation has been demonstrated.

The Liebeskind–Srogl Cross‐Coupling Reaction and its Synthetic Applications

“…Very recently, the Jiang group reported a new and efficient Pd 0 ‐catalyzed, Cu I ‐mediated C−S functionalization of 3‐sulfenylheteroarenes (Scheme ) . This procedure can serve as a powerful synthetic tool for the construction and late‐stage modification of important heteroarene scaffolds.…”

Palladium-Catalyzed Carbothiolation of Alkenes and Alkynes for the Synthesis of Heterocycles

“…29,39,97−101 We initially focused on the evaluation of phosphine ligands since they have been used in related intramolecular carbofunctionalization reactions and are capable of activating the C(sp 2 )−S bond. 90,95 However, surprisingly, none of the employed ligands showed any competence in forming the desired product (entries 2−4, see also Supporting Information Table S1). We next evaluated a series of sterically crowded N-heterocyclic carbene (NHC) ligands, which our group and others had previously identified as a valuable scaffold in the activation of thioethers.…”

“…To realize the carbothiolation reaction and obtain the desired heterocyclic thioether products, we envisioned an approach similar to the previously reported methods. ,,, The oxindole-motif (product 1 ) was further targeted due to its presence in several bioactive molecules and its use as an intermediate in the synthesis of several natural products. ,− With this strategy in mind, and based on our recent interest in C–S bond manipulation, we set out to find a suitable catalytic system (Table ). − Since various Pd catalysts have already been proven to be competent in catalyzing transformations of thioether derivatives, we began our investigations using Pd 2 dba 3 as a precatalyst. ,,− We initially focused on the evaluation of phosphine ligands since they have been used in related intramolecular carbofunctionalization reactions and are capable of activating the C­(sp 2 )–S bond. , However, surprisingly, none of the employed ligands showed any competence in forming the desired product (entries 2–4, see also Supporting Information Table S1). We next evaluated a series of sterically crowded N -heterocyclic carbene (NHC) ligands, which our group and others had previously identified as a valuable scaffold in the activation of thioethers. − Conversion of the starting material to the cyclized product was observed when IPr (1,3-bis­(2,6-diisopropylphenyl)-1,3-dihydro-2 H -imidazole-2-ylidene) was employed.…”

CuSO4-Catalyzed Tandem C(sp3)–H Insertion Cyclization of Toluenes with Isonitriles to Form Indoles

“…3-Alkylthioindoles can be directly used for cross-coupling. 8 To explore the reaction mechanism, control experiments were performed. In the radical trapping experiment, 1a-OTEMP adduct 6 was isolated in 49% yield (eq 1), indicating that a benzylic radical might be involved.…”

“…In another case, 3a was oxidized to 3-sulfonyl indole 5 . 3-Alkylthioindoles can be directly used for cross-coupling …”