Synthesis of Monofluoromethyl Selenoethers of Aryl and Alkyl from Organoselenocyanate via One‐Pot Reaction

Abstract

The first practical and feasible approach for the monofluoromethylselenolation of aryl and alkyl halides via one-pot multistep synthesis using KSeCN and ICFH 2 is described. Good yields and broad functional group compatibility were obtained. The successful preparation of monofluoromethylselenolated drug-like compounds good practicability of this method. This protocol offered a number of new monofluoromethyl selenoethers, which would accelerate the use of such compounds in the areas of life science.

Metal‐Free Synthesis of Aryl Selenocyanates and Selenaheterocycles with Elemental Selenium

“…Over the past decade, aryl selenocyanates (ArSeCN) have attracted considerable attention since they displayed biological activity [2] and found wide applications in organic synthesis. For example, aryl selenocyanates have appeared as an important organoselenium reagent to construct various organic selenium compounds including monoselenides, [3a–e] diselenides, [3f,g] trifluoromethyl (difluoromethyl) selenides, [3h,i] selenoesters [3j] and selenium‐containing ligands [3k] . In some cases, aryl selenocyanates could serve as a useful bifunctional reagent for the direct cyanoselenenylation of unsaturated C−C bonds [4]…”

Se‐(Fluoromethyl) Benzenesulfonoselenoates: Shelf‐Stable, Easily Available Reagents for Monofluoromethylselenolation

“…In 2019, the first approach of the monofluoromethylselenolation was reported by Yi and co‐workers (Figure 1a); [11a] the procedure started from the conversion of anilines into aryldiazonium tetrafluorobotates through Sandmeyer‐type chemistry, followed by subsequent copper‐mediated reactions with KSeCN to form selenocyanates which were treated with KOH to furnish diselenides, then underwent an electrophilic substitution of ICFH 2 to afford the monofluoromethylselenolated products. And alkyl selenocyanates were prepared from alkyl bromides with subsequent similar processes.…”

Direct and Chemoselective Electrophilic Monofluoromethylation of Heteroatoms (O-, S-, N-, P-, Se-) with Fluoroiodomethane

“…The method proved to be modular as indicated by the synthesis of a selenium derivative (46), previously prepared through a complex sequence involving aniline diazotizationconversion into organoselenocyanateformation of a diselenide, and finally transfer of a RSe − anion to FIM. 30 To cover the range of nucleophilic groups amenable for the proposed functionalization, we then demonstrated the validity Organic Letters pubs.acs.org/OrgLett Letter of the technique for medicinally important nitrogenated heterocycles (Scheme 4). The purinic base stimulant drug theophylline (47) or the prototypal histaminic-H 2 antagonist cimetidine was selectively fluoromethylated at positions 7 and 1 (the guanidine portion remaining unaffected), respectively.…”

“…The higher acidity of a thiophenol (compared to an aliphatic alcohol) rendered feasible the transformation for the trityl derivative ( 44 ), whereas an excess of FIM and Cs 2 CO 3 enabled the double functionalization on both oxygen and sulfur sites of thiosalicylic acid ( 45 ). The method proved to be modular as indicated by the synthesis of a selenium derivative ( 46 ), previously prepared through a complex sequence involving aniline diazotizationconversion into organoselenocyanateformation of a diselenide, and finally transfer of a RSe – anion to FIM …”