Iron-Promoted Construction of Indoles via Intramolecular Oxidative C–N Coupling of 2-Alkenylanilines Using Persulfate

Abstract

Indole scaffold synthesis relies primarily on oxidative C–H amination of N-protected alkenylanilines for C–N intramolecular cyclization reactions. Herein, for the first time, without N-protection, various readily prepared 2-alkenylanilines were transformed into the desired indole products in good yields by using K2S2O8 as oxidant in the presence of catalytic amounts of FeF2. The K2S2O8/FeF2 system offers a direct and benign synthetic route to 3-arylindoles and it is applicable to a wide range of substituted indoles including drug intermediates.

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

“…Terminal alkenes bearing an alkyl or phenyl group at the R 2 position cyclized smoothly to generate 3-substituted indoles (4−6). Trisubstituted alkenes, both acyclic (7,8) and cyclic ones (9−13), all reacted successfully to afford 2,3disubstituted indoles. The benzene ring tolerated substituents of various electronic properties such as alkyl groups (14,15), halides (16−18), CF 3 O (19), and CF 3 (20).…”

“…8 White solid (50 mg, 84%) (petroleum ether/EtOAc = 25:1), electricity = 2.3 F mol −1 . 1 2-Ethyl-3-methyl-1-tosyl-1H-indole (7). 55 Pale blue oil (62 mg, 96%) (petroleum ether/EtOAc = 20:1), electricity = 2.3 F mol −1 .…”

“…The residue was chromatographed through silica gel to afford 12s as yellow solid (0.46 g, 38%) (petroleum ether/EtOAc = 25:1). 1 N-(2-(6,7-Dihydro-5H-benzo [7]annulen-9-yl)phenyl)-4methylbenzenesulfonamide (13s). To a mixture of 4-methyl-N-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzenesulfonamide (0.93 g, 2.5 mmol), 6,7-dihydro-5H-benzo [7]annulen-9-yl trifluoromethanesulfonate (1.2 g, 4.1 mmol), Pd(PPh 3 ) 4 (0.15 g, 0.13 mmol), and K 2 CO 3 (1.1 g, 8.0 mmol) was added a 1:1:2 (v/v/v) mixture of EtOH/H 2 O/toluene (12 mL).…”

“…The development of efficient and sustainable synthetic methods to access indoles has been constantly pursued by organic chemists because of the prevalence of the indole moiety in bioactive compounds and natural products. , Among various methods for the synthesis of indoles, the oxidative cyclization of 2-vinylanilines provides regio-specific access to functionalized indoles from easily available materials. These reactions are commonly achieved using chemical oxidants with − or without − transition metal catalysts (Scheme A). The use of chemical oxidants in organic solvents not only pose significant safety and environmental concerns, but also produce stoichiometric waste products that may complicate product isolation and interfere with the desired transformation .…”

Selenium‐Mediated Cyclization Reaction of 2‐Vinylanilines with/without Isonitriles: Efficient Synthesis of 2‐Aminoquinoline/ 3‐Aryl‐1H‐indole Derivatives

“…Including cyclization of 2‐vinylanilines used Cu(OAc) 2 as an accelerant, used PIFA as an oxidant . Recently, Li et al . have reported the synthesis of 3‐aryl‐1 H ‐indoles by K 2 S 2 O 8 oxidized cyclization of 2‐(1‐arylvinyl) anilines in the presence of catalytic amounts of FeF 2 .…”