I2-Catalyzed sulfenylation of indoles and pyrroles using triethylammonium thiolates as sulfenylating agents

Abstract

Readily available triethylammonium thiolates were proven to be new and eco-friendly sulfenylating agents for the efficient and practical construction of sulfenylated indoles and pyrroles (48 examples) with good to excellent yields under metal-free and microwave irradiation conditions. The combination of I₂ and DMSO enabled direct C-S bond formation, allowing easy and low-cost access to new functionalized C,S-tethered bisindoles and pyrrole-indole pairs with a wide diversity of substituents. The mechanism involving S-S and S-I bond-forming/breaking events was proposed.

Figure 1

Bioactive compounds containing 3-sulfenylindole skeleton

Figure 2

X-Ray structure of 4d

Scheme 1

Metal-free sulfenylation of indoles and pyrroles

Scheme 2

Substrate scope for the synthesis of products 4. (i) Isolated yields based on triethylammonium thiolates 1 by column chromatography. (ii) All reactions were performed with triethylammonium thiolates 1 (1.0 mmol), indoles 2 (1.0 mmol), I₂ (0.2 mmol), and DMSO (2.0 mL) in the sealed reaction tube at 120 °C under microwave conditions for 1 h.

Scheme 3

Substrate scope for the synthesis of products 5. (i) Isolated yields based on triethylammonium thiolates 1 by column chromatography. (ii) All reactions were performed with triethylammonium thiolates 1 (1.0 mmol), pyrroles 3 (1.0 mmol), I₂ (0.2 mmol), and DMSO (2.0 mL) in the sealed reaction tube at 120 °C under microwave conditions for 1 h.

Scheme 4

Substrate scope for the synthesis of products 7. (i) Isolated yields based on triethylammonium thiolates 6 by column chromatography. (ii) All reactions were performed with triethylammonium thiolates 6 (1.0 mmol), indoles 2 (or pyrroles 3, 1.0 mmol), I₂ (0.2 mmol), and DMSO (2.0 mL) in the sealed reaction tube at 120 °C under microwave conditions for 1 h.

Scheme 5

Control Experiments

Scheme 6

Proposed mechanisms for forming products 4 and 5