Stereoselective synthesis of sulfur-containing β-enaminonitrile derivatives through electrochemical Csp3–H bond oxidative functionalization of acetonitrile

Abstract

Incorporation of nitrile groups into fine chemicals is of particular interest through C(sp3)–H bonds activation of alkyl nitriles in the synthetic chemistry due to the highly efficient atom economy. However, the direct α-functionalization of alkyl nitriles is usually limited to its enolate chemistry. Here we report an electro-oxidative C(sp3)–H bond functionalization of acetonitrile with aromatic/aliphatic mercaptans for the synthesis of sulfur-containing β-enaminonitrile derivatives. These tetrasubstituted olefin products are stereoselectively synthesized and the stereoselectivity is enhanced in the presence of a phosphine oxide catalyst. With iodide as a redox catalyst, activation of C(sp3)–H bond to produce cyanomethyl radicals proceeds smoothly at a decreased anodic potential, and thus highly chemoselective formation of C–S bonds and enamines is achieved. Importantly, the process is carried out at ambient temperature and can be easily scaled up.

Direct C(sp3)−H Sulfonylation and Sulfuration Reactions of Isoquinoline‐1,3(2H,4H)‐diones under Metal‐free Conditions

“…The transition metal‐free sulfuration reaction has been a key issue in C−S bond formation [1a,6] . In particular, the t ‐BuOK‐promoted sulfuration reaction using diaryl disulfides as the sulfur source has attracted a lot of attention [3,7] and, in most cases, they have been confirmed as an electrophilic addition process.…”

Electrochemical Synthesis of Sulfinic Esters from Alcohols and Thiophenols

“…[38][39] Based on the experimental results and previous literature reports. [5][6][7][8][9][10][11][12][13][14] A preliminary reaction mechanism is proposed in Scheme 5b. The thiol radicals B, which could be generated via oxidation and deprotonation of thiophenol A on the anode, dimerize to form disulfane C. The following oxidation of C by O 2 would lead to the generation of thiosulfinates D, which would go through the nucleophilic substitution process with alcohol to access target product.…”

“…More specifically, when it comes to electrochemical transformations of S-H bonds, a series of fruitful achievements have been made in the past three years. As shown in Scheme 1, starting from thiophenols, dehydrogenative oxidative couplings between thiophenols (S-H) and (hetero)arenes (C-H, Scheme 1a), [10][11] enamines (C-H, Scheme 1a), 12 acetonitrile (C-H, Scheme 1a), 13 amines (N-H, Scheme 1b), 14 thiols (S-H, Scheme 1c), [15][16] thiophenols (S-H, Scheme 1c) 17 , aryl sulfinic acids (Scheme 1c) 18 or phosphonate (P-H, Scheme 1d) [19][20] have been achieved with the assistance of electricity. 21 Generally, no additional oxidants or catalysts were required for such transformations, and S-H bonds could be cleaved with retention of sulphur's oxidation state.…”

Electrochemical Generation and Use in Organic Synthesis of C‐, O‐, and N‐Centered Radicals

“… Huang's iodide mediated synthesis sulfur‐containing β‐enaminonitrile derivates in anodic conditions [115] …”