Electrochemical C−H Amidation of Heteroarenes with N‐Alkyl Sulfonamides in Aqueous Medium

Abstract

The constructiono fC ÀNb onds by free radical reactions represents ap owerful synthetic approach for direct CÀHa midationso fa renes or heteroarenes. Developing efficient and more environmentally friendly synthetic methods for CÀHa midationr eactions remains highly desirable. Herein, metal-free electrochemical oxidative dehydrogenative CÀHa midations of heteroarenes with N-alkylsulfonamides have been accomplished. The catalystand chemical-oxidant-free CÀHa midation featuresa n ample scope and employs electricity as the green and sole oxidant. Av arietyo fh eteroarenes, including indoles, pyrroles, benzofuran and benzothiophene, thereby underwent this C(sp 2)ÀHn itrogenation. Cyclic voltammetry studiesa nd control experiments provided evidence for nitrogen-centered radicals being directlyg enerated under metal-free electrocatalysis. Scheme1.Strategies for directC ÀHa midation of heteroarenes.

Photochemical and Electrochemical Applications of Proton-Coupled Electron Transfer in Organic Synthesis

“…Recently, Zhang, Ackermann and co-workers disclosed a protocol for the electrochemical C(sp 2 )–H sulfonamidation of heteroarenes via N–H bond concerted PCET activation in an N -alkyl sulfonamide coupling partner ( Scheme 49 ). 199 Optimal conditions consisted of the constant current electrolysis of heteroarene and sulfonamide coupling partners in 1,4-dioxane/H 2 O (1:1) solution in an undivided electrochemical cell equipped with graphite felt anode and Pt cathode at 80 °C. K 3 PO 4 served as both the electrolyte and the Brønsted base additive.…”

“…K 3 PO 4 significantly negatively shifted the oxidation potential of the sulfonamide (e.g., for N -methyl p -toluenesulfonamide, E 1/2 ox = +2.50 V vs Ag/AgCl in MeCN, compared to E 1/2 ox = +1.00 V vs Ag/AgCl in MeCN/0.2 M aq. K 3 PO 4 solution), 199 suggesting that K 3 PO 4 serves as both the electrolyte and base to facilitate concerted PCET activation of the sulfonamide substrate. Based on these studies, the authors propose a mechanism wherein the sulfonamide substrate undergoes concerted PCET at the anode to generate an intermediate N -sulfonamidyl radical.…”

Electro-Oxidative C–N Bond Formation through Azolation of Indole Derivatives: An Access to 3-Substituent-2-(Azol-1-yl)indoles

“…In recent years, electrochemistry, utilizing electric current as an inexpensive, renewable, and inherently safe reagent to replace stoichiometric amounts of dangerous, wasteful, and ultimately unnecessary oxidant/reductant during the oxidative or reductive transformations, has been established as an atom-economic and increasingly powerful green strategy for organic synthesis. − In this field, considerable progress has been accomplished in the intramolecular C­(sp 2 )–N bond formation. − To date, the synthetically useful methodologies for intermolecular C–N bond formation are still limited. − As our ongoing interest in the construction of the C–N bond via electrochemistry transformation, a series of electrochemical oxidative intermolecular C­(sp 2 /sp 3 )–N bond formation reaction has been developed. , To continue our efforts in electrochemical transformation, we envisioned that the azolation of five-membered indole ring could be achieved via an electro-oxidative heteroarene amidation pathway through tuning the electro-nature of indoles with different N-protecting groups. Recently, Ackermann and co-workers developed a novel electrochemical oxidative dehydrogenative C–H amidation protocol with N-alkyl protected indoles and N-alkylsulfonamides (Figure c) . We report here that, under constant cell potential at room temperature, the N-acyl protected indoles could couple with various azoles in good efficiency (Figure ).…”

“…Recently, Ackermann and co-workers developed a novel electrochemical oxidative dehydrogenative C−H amidation protocol with N-alkyl protected indoles and Nalkylsulfonamides (Figure 1c). 48 We report here that, under constant cell potential at room temperature, the N-acyl protected indoles could couple with various azoles in good efficiency (Figure 1).…”

Organic Electrosynthesis Towards Sustainability: Fundamentals and Greener Methodologies

“…Nowadays, a large number of other relevant molecules, such as heterocycles, common biological active scaffolds, are being synthesized by direct electrosyntheses. The green preparation of isocoumarin derivatives by continuous flow from o ‐(1‐alkynyl) benzoates, [51] the catalyst‐free electrosynthesis of benzimidazolones through an intramolecular oxidative C−N coupling, [52] the formation of pyrrolidines by oxidative C(sp 3 )−H amination [53] and the electrochemical C−H amidation of heteroarenes with N ‐alkyl sulfonamides in aqueous media demonstrate this fact [54] . Moreover, synthesis of higher functionalized lactones, through an anodic radical coupling pathway, has been performed recently under mild and green conditions with a wide scope of substrates [55] .…”