Synthesis of Thiocarbamoyl Fluorides and Isothiocyanates Using Amines with CF₃SO₂Cl

Abstract

A practical and efficient method to synthesize thiocarbamyl fluorides and isothiocyanates from amines with trifluoromethanesulfonyl chloride was developed. In the presence of the reducing agent triphenylphosphine and sodium iodide, thiocarbamyl fluorides and isothiocyanates were synthesized from secondary/primary amine in moderate to excellent yields, respectively. A broad scope of substrates and good functional group compatibility were observed.

A more sustainable isothiocyanate synthesis by amine catalyzed sulfurization of isocyanides with elemental sulfur

“…anti-cancer, [25][26][27][28][29][30][31][32][33] anti-inammatory, [34][35][36][37][38] antimicrobial, 39 antibiotic, 39 antibacterial, 40 fungicidal 41 or insecticidal activity. 42,43 Commonly, they are synthesized by using thionyl transfer agents (thiophosgene, its derivatives, 2,[44][45][46][47][48] or, more recently, uorinated agents) [49][50][51][52][53][54] or via the formation of dithiocarbamate salts with carbon disulde under basic conditions, followed by desulfurization (Scheme 1a). 44,[55][56][57] These approaches are usually chosen due to the easy access of the respective amines, which can be transferred quickly to the ITC in one or two steps.…”

Sulforaphane and Its Bifunctional Analogs: Synthesis and Biological Activity

“…Recently, Wei et al [ 231 ] published an efficient method synthesis of a library of isothiocyanates from primary amines using trifluoromethanesulfonyl chloride in the presence of reducing the agent triphenylphosphine and sodium iodide ( Figure 14 , path f ). Trifluoromethanesulfonyl chloride (CF 3 SO 2 Cl) is commercially available, cheap, easy to handle, and widely used (e.g., in electrophilic chlorination [ 232 ], trifluoromethylation [ 233 ], or in chloro-trifluoromethylthiolation of alkenes and alkyne [ 234 ]) reagents.…”

Deoxygenation of ClSO2CF2COOMe with Triphenylphosphine for the Metal-Free Direct Electrophilic Difluoroalkylthiolation of Various Heterocycles

“…According to previous work, ClSO 2 CF 2 COOMe is easily derived from Chen’s reagent and was used as the SCF 2 COOMe resource. We began our investigations by optimizing the reaction between ClSO 2 CF 2 COOMe and indole ( 1a ) in the presence of triphenylphosphine (PPh 3 ) as reductant (Table S5 in Supporting Information).…”

“…We speculated that if FSO 2 CF 2 COOMe can serve as an electrophilic reagent with its ester group retained and introduced into the organic substrate, its application range would be further expanded. Inspired by a recent advance in direct electrophilic fluoroalkylthiolation using R f SO 2 Na or R f SO 2 Cl as the fluoroalkylthio source, we envisioned utilizing ClSO 2 CF 2 CO 2 Me derived from FSO 2 CF 2 COOMe as a new electrophilic difluoroalkylthiolation reagent. Herein, we report a metal-free route for direct electrophilic difluoroalkylthiolation of indoles and other electron-rich heterocycles using ClSO 2 ­CF 2 ­COOMe (Scheme e).…”