Water enables the tunable electrochemical synthesis of heterocyclic 3a- or 5a-bromoindolines

Abstract

Due to the electron-richness of the C3/C2 positions of the indole moiety, direct nucleophilic bromination at the C5-position of tryptophol and tryptamine derivatives is difficult and remains unexplored. Herein, we...

Electrochemical bromocyclization enables 3,5-diversification of heterocyclic indolines

“…Furthermore, in our previous work, 11 a 2.5/1.5 (v/v) mixture of acetonitrile and water enabled highly selective 5-bromocyclization to form the 5-bromoindoline 19 , and none of 3,5-dibromoindoline 2a was observed (Scheme 6, eqn (1)). The mechanism of the formation of 5-bromoindoline has been verified through a key reductive hydrodebromination of 3a-bromofuranindoline at the cathode.…”

“…Several control experiments were conducted to investigate the functions of the Brønsted acid. In our previous work, 11 a 4/0.1 (v/v) mixture of acetonitrile and water enabled highly selective 3-bromocyclization ( 3a : 83% yield), and only a trace amount of 3,5-dibromoindoline 2a was observed (Scheme 5, eqn (1)). When CH 3 COOH was added under such conditions, the 3,5-dibromoindoline 2a was obtained as the final product in 84% yield after same reaction time (Scheme 5, eqn (2)).…”

“…Recently, as a new advance in this transformation, our group 11 reported a tunable electrochemical synthesis of heterocyclic 3a- or 5a-bromoindolines with non-hazardous NaBr as both the electrolyte and Br source (Scheme 2a, path ii). Mechanistic studies revealed that the heterocyclic 5a-bromoindoline was formed via collaborative electrooxidation of bromide ions at the anode and reductive hydrodebromination of 3a-bromofuranindoline at the cathode in a single undivided cell (Scheme 2a and b).…”

Synthesis of Pyrazolidinone-Fused Benzotriazines through C–H/N–H Bond Functionalization of 1-Phenylpyrazolidinones with Oxadiazolones

“…Synthesis of 7. 15 A reaction tube equipped with a stir bar was charged with 3 h (74.1 mg, 0.2 mmol), dioxane (2 mL), Pd(dba) 3 (18.3 mg, 0.02 mmol), DavePhos (11.8 mg, 0.03 mmol), t-BuONa (38.4 mg, 0.4 mmol), and morpholine (52.3 mg, 0.6 mmol). The tube was then sealed, and the resulting mixture was stirred at 100 °C (oil bath) under argon for 12 h. Upon completion, it was diluted with dichloromethane (20 mL) and washed with water and brine.…”

Electrochemical oxidation of 3-substituted indoles

“…Chemical oxidants are a well-established tool for this transformation [14][15][16][17][18][19][20][21][22][23][24][25][26][27] (Scheme 1A), but these reagents present safety and downstream pollution issues. A mild and green alternative to harsh chemical oxidants is electrochemical oxidation; [28][29][30] several anodic transformations of indoles have been reported, [31][32][33][34][35][36][37][38][39] but two recent reports describing the electrochemical oxidative rearrangement of tetrahydroβ-carbolines (Scheme 1B) 40,41 prompts disclosure of our own efforts in this area (Scheme 1C).…”