Electrochemical Regioselective Sulfenylation of 2H-Indazoles with Thiols in Batch and Continuous Flow

Abstract

A novel electrochemical cross-dehydrogenative C–S bond coupling of aryl thiols with 2H-indazole is reported. Thiol-functionalized 2H-indazoles were synthesized under catalyst-, oxidant-, and metal-free conditions with innocuous hydrogen as the sole byproduct at ambient temperature. Furthermore, continuous electrochemical flow conditions using a graphite/Ni flow cell were used to obtained 3-(arylthio)-2H-indazole compounds on a gram scale within the residence time of 39 min. Detailed mechanistic studies including control experiments and cyclic voltammetry are provided to support the radical–radical cross-coupling pathway.

Metal-Free Synthesis of 2H-Indazole Skeletons by Photochemistry or Thermochemistry

“…A 100 mL oven-dried reaction vessel equipped with a magnetic stir bar 144.7, 135.7, 131.8, 129.9, 129.4, 128.8, 121.8, 119.6, 118.3, 117.2, 53.1, 51.6, 21.8, 21.6, 12.2 CDCl 3 ) δ: 7.58 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 9.6 Hz, 1H), 7.24 (d, J = 7.8 Hz, 2H), 6.98 (dd, J = 9.6, 2.4 Hz, 1H), 6.63 (d, J = 2.4 Hz, 1H), 4.95 (s, 2H), 3.74 (s, 3H), 3.14−3.08 (m, 2H), 2.93−2.88 (m, 2H), 2.40 (s, 3H), 0.77 (t, J = 6.6 Hz, 6H). 13 C{ 1 H} NMR (150 MHz, CDCl 3 ) δ: 155. 6, 145.1, 142.4, 135.7, 129.9, 128.8, 121.6, 121.5, 119.4, 119.0, 96.4, 55.2, 53.1, 51.6, 21.6, 12…”

“…1 H NMR (600 MHz, CDCl 3 ) δ: 7.77 (dd, J = 9.0, 1.2 Hz, 1H), 7.62−7.61 (m, 2H), 7.56 (t, J = 1.2 Hz, 1H), 7.38 (dd, J = 9.0, 1.8 Hz, 1H), 7.32 (d, J = 7.8 Hz, 2H), 4.99 (s, 2H), 3.20 (br, 2H), 3.10 (br, 2H), 2.49 (s, 3H), 0.85 (t, J = 7.2 Hz, 6H). 13…”

Cell Voltage-Dependent Structural Dichotomy: Electrochemical C–H Acyloxylation and N-Acylation of 2H-Indazoles

“…Hence, on the basis of CV studies, control experiments (see Supporting Information 4), and previous reports, a plausible mechanism was proposed for the electrochemical oxidative N-1 migratory acylation through C-3 acyloxylation of 2 H -indazoles as depicted in Scheme . Aryl carboxylic acid [ A ] was ionized into carboxylate ion [ B ] through proton abstraction by K 2 CO 3 .…”

Disulfides as versatile starting reagents: effective sulfonylation of alkenes with disulfides under electrochemical conditions

“…The products of such transformations can also be applied in synthetic chemistry and possess promising biological properties. Two main directions exist in this field: sulfenylation [23][24][25][26][27][28] and sulfonylation [29][30][31][32] processes. Thiols are usually applied as sulfenylating agents for various unsaturated compounds (Scheme 1a).…”