Iodine-Mediated Electrochemical C(sp²)–H Amination: Switchable Synthesis of Indolines and Indoles

Abstract

Unless otherwise noted, materials were obtained from commercial suppliers and used without further purification. NMR spectra were recorded on a Bruker AV-400 ( 1 H: 400 MHz, 13 C:100 Hz) spectrometer using TMS as internal reference. Chemical shifts (δ) and coupling constants (J) were expressed in ppm and Hz, respectively. The following calibration was used: CDCl3 δ = 7.26 and 77.16 ppm. High resolution mass spectra (HRMS) were measured using electrospray ionization (ESI) and the time-of-flight (TOF) mass analyzer. The instrument for electrolysis is DC regulated power supply (HY3005M, made in China). The anode electrode and cathode electrode all are Pt (1.5 × 1.5 × 0.3 cm 3 ). These electrodes are commercially available from GaossUnion, China.Commercially available compounds were used as received without further purification.The start materials including substituted 4-methyl-N-(2-vinylphenyl)benzenesulfonamide compounds, 1 Nsubstituted 2-vinylanilines, all were known and synthesized according to literature procedures. 2 Experimental ProcedureGeneral procedure A for the electrosynthesis of diamination indoline: An undivided cell was equipped with a magnet stirrer, platinum plate (1.5 × 1.5 × 0.3 cm 3 ) electrode, as the working electrode and counter electrode. The substrate 2-vinyl aniline 1 (0.3 mmol), amine 2 (0.3 mmol), Me4NI (20 mol %, 12.1 mg) and NH4PF6 (0.3 mmol, 49.9 mg) were added to the solvent CH3CN/H2O (5 mL/1 mL). The electrolysis was conducted in an undivided cell at a constant current of 5 mA at room temperature (25°C). After the reaction was completed, the solvent was removed under reduced pressure and the remaining crude product was purified by column chromatography over silica gel (PE/EtOAc = 20/1) to afford the corresponding indoline product.General procedure B for the electrosynthesis of indole: An undivided cell was equipped with a magnet stirrer, platinum plate (1.5 × 1.5 × 0.3 cm 3 ) electrode, as the working electrode and counter electrode. The substrate 2vinyl aniline 1 (0.3 mmol), Me4NI (0.3 mmol, 60.3 mg) and KSCN (0.3 mmol, 29 mg) were added to the solvent CH3CN/H2O (5 mL/1 mL). The electrolysis was conducted in an undivided cell at a constant current of 5 mA at oil bath (80°C). After the reaction was completed, the solvent was removed under reduced pressure and the remaining crude product was purified by column chromatography over silica gel (PE/EA = 30/1) to afford the corresponding indole product.Gram-scale synthesis of 3aa: An undivided cell was equipped with a magnet stirrer, platinum plate (1.5 × 1.5 × 0.3 cm 3 ) electrode, as the working electrode and counter electrode. The substrate 2-vinyl aniline 1a (6 mmol, 1.64 g), phenylamine 2a (6 mmol, 559 μL), Me4NI (3 mmol, 603.2 mg) and Me4NPF6 (6 mmol, 978 mg) were added to the solvent CH3CN/H2O (100 mL/20 mL). The electrolysis was electrolyzed (I = 20 mA, 8.9 mA/cm 2 ) in an undivided cell at room temperature (25°C). After the reaction was completed (about 24 h), the reaction system was allowed to attain room temperature. Then the rea...

Urethanes synthesis from oxamic acids under electrochemical conditions

“…The role of a supporting electrolyte was also studied, showing that tetrabutylammonium perchlorate (n-Bu4NClO4) 11b did not bring any improvement (entry 10), while n-Bu4NI led to a drastic decrease in yield, possibly as a result of its competitive decomposition at the anode (entry 11). 13 Finally, the nature of electrodes was investigated. The use of a platinum anode significantly decreased the yield (entry 12), while stainless steel did not provide the product at all (entry 13).…”

Electrocatalytic Dehydrogenative Cyclization of 2-Vinylanilides for the Synthesis of Indoles

“…This feature makes electrochemistry a highly attractive tool to address the “oxidant problem” . In this context, many electrochemical methods have been developed for the synthesis of heterocycles through dehydrogenative processes. − Related to this work, Wang and co-workers have reported iodide mediated electrochemical cyclization of 2-vinylanilides for the synthesis of indoles that bear no substituents at positions 2 and 3 (Scheme B) . With our continued interests in electrochemically driven radical reactions, − we report herein an electrocatalytic method for the synthesis of 3-substituted and 2,3-disubstituted indoles (Scheme C).…”

“…31−33 Related to this work, Wang and coworkers have reported iodide mediated electrochemical cyclization of 2-vinylanilides for the synthesis of indoles that bear no substituents at positions 2 and 3 (Scheme 1B). 34 With our continued interests in electrochemically driven radical reactions, 35−39 we report herein an electrocatalytic method for the synthesis of 3-substituted and 2,3-disubstituted indoles (Scheme 1C). The reactions employ an organic redox catalyst and provides metal-and oxidant-free access to functionalized indoles.…”

Electrifying Sustainability on Transition Metal‐Free Modes: An Eco‐Friendly Approach for the Formation of C−N Bonds

“…Similar to Scheme 11, Wang and co‐workers [31] reported iodide‐mediated intramolecular amination starting from N‐protected 2‐vinyl aniline (Scheme 20). The authors demonstrated the compatibility of this amination reaction by showing different aromatic amines (primary and secondary) with both electron‐donating and ‐withdrawing functionalities along with cyclic amines, such as cyclohexylamine and piperidine.…”