Ag/Pyridine Co-Mediated Oxidative Arylthiocyanation of Activated Alkenes

Abstract

An efficient Ag/pyridine co-mediated oxidative arylthiocyanation of activated alkenes via radical addition/cyclization cascade process was developed. This reaction could be carried out under mild conditions to provide biologically interesting 3-alkylthiocyanato-2-oxindoles in good to excellent yields. Mechanistic studies suggested a unique NCS• radical addition path and clarified the dual roles of catalytic pyridine as base and crucial ligand to accelerate the oxidation of Ag(I) to Ag(II), which is likely oxidant responsible for the formation of NCS• radical. These mechanistic results may impact the design and refinement of other radical based reactions proceeding through catalytic oxidations mediated by Ag(I)-pyridine/persulfate. The chemical versatility of thiocyanate moiety was also highlighted via SCN-tailoring chemistry in post-synthetic transformation for new S-C(sp3/sp2/sp), S-P, and S-S bonds constructions. The protocol provides an easy access to many important bioisosteres in medicinal chemistry and an array of sulfur-containing 2-oxindoles that are difficult to prepare by other approaches.

Recent progress of direct thiocyanation reactions

“…An efficient Ag/pyridine co-mediated oxidative arylthiocyanation of activated alkenes via a radical addition/cyclization cascade process was documented by Feng et al in 2018. 55 Thiocyanato substituted 2-hydroxyindole 173 was prepared using N-methyl-N-phenylmethylacrylamide 172 as the substrate and AgSCN as the thiocyanating reagent under a nitrogen atmosphere at 75 °C for 2 hours, as shown in Scheme 48. Firstly, pyridine was coordinated with Ag(I) and then oxidized by sulfate to form a Ag(II)-pyridine complex, which further oxidized SCN − to generate SCN Hypervalent iodine is also a common oxidant, which can be used to produce the SCN radical.…”

Sustainable Synthetic Approaches Involving Thiocyanation and Sulfur- Cyanation: An Update

“…In the case of one example with an alkyl substituent on the triple bond, acetonitrile was the best solvent, however, a lower yield of 22% was obtained. The arylthiocyanation of activated alkenes (75) was developed by using a silver thiocyanate/pyridine-mediated oxidative SCN-radical addition/cyclization domino process [32]. The reaction led to 3-alkylthiocyanato-2-oxindoles (76) in good to excellent yields (Scheme 32).…”

Sustainable Synthetic Approaches Involving Thiocyanation and Sulfur- Cyanation: An Update

“…The N-alkenoxypyridinium salts, easily prepared by goldcatalyzed addition of pyridine N-oxide to alkynes, have been used as umpoled enolates to introduce a thiocyanate function in α-position of a ketone [12]. The N-alkenoxypyridinium salt (32) reacted with KSCN in acetonitrile leading to various α-thiocyanated ketones (33) in good yields and with excellent functional group tolerance (Scheme 12). Pyridine and KNTf 2 were produced at the same time.…”

“…Two mechanistic pathways were proposed, involving either an iodonium ion or a sulfonium ion intermediate. The arylthiocyanation of activated alkenes (75) was developed by using a silver thiocyanate/pyridine-mediated oxidative SCN-radical addition/cyclization domino process [32]. The reaction led to 3-alkylthiocyanato-2-oxindoles (76) in good to excellent yields (Scheme 32).…”