Electrophilic (Ethoxycarbonyl)difluoromethylthiolation Using Difluoroalkyl Sulfonium Salts

Abstract

We report a simple protocol for (ethoxycarbonyl)difluoromethylthiolation of nucleophilic compounds using a difluoroalkyl sulfonium salt which can be in situ prepared via Tf2O triggered electrophilic activation of a benzyl difluoroalkyl sulfoxide. With the protocol, difluoroalkylthiolated arenes, heteroarenes and α-difluoroalkylthiolated carbonyl compounds etc. were obtained smoothly with good to excellent yields. Merits of the reaction include the readily available difluoroalkylthiolation reagent and substrates, mild conditions, and excellent regioselectivity.

β-Trifluorosulfinylesters: tuneable reagents for switchable trifluoromethylsulfinylation and C–H trifluoromethylthiolation

“…A suitable base facilitated the removal of leaving parts in the last step and the final product 8 or 10 was selectively generated. 11,22…”

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

“…1 H NMR (CDCl 3 , 400 MHz) δ: 7.83−7.81 (m, 1H), 7.61 (s, 1H), 7.56−7.48 (m, 5H), 7.44−7.40 (m, 1H), 7.32−7.26 (m, 2H), 3.73 (s, 3H); 19 F NMR (CDCl 3 , 376 MHz) δ: − 83.42 (s, 2F); 13 C{ 1 H} NMR (CDCl 3 , 101 MHz) δ: 162.6 (t, J = 32.8 Hz), 138. 7,136.7,136.2,131.0,130.0 (2C),127.7,124.8 (2C),123.7,122.8,119.9 (t,J = 287.4 Hz),119.8,111.2,96.4,53.8 137.8,127.3,126.7,124.7,120.3,120.0,119.7 (t,J = 289.5 Hz),113.9,111.4,54.3,33,6,25.6,24, Methyl 2-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-ylthio)-2,2-difluoroacetate (2aa). Pale yellow solid, 101 mg, 85% yield, mp 56−58 °C (purified by silica gel flash column chromatography eluted with petroleum ether/ethyl acetate = 3:1, v/v).…”

“…However, to our best knowledge, very few methods are available for efficient and direct introduction of the −SCF 2 CO 2 R group into organic molecules until four elegant difluoroalkylthiolating reagents have emerged recently, i.e. PhNHSCF 2 CO 2 Me, [[(ethoxycarbonyl)-difluoromethyl]­thio]­phthalimide (R–NSCF 2 ­CO 2 Et), ArSO 2 SCF 2 CO 2 Et, and BnS­(O)­CF 2 CO 2 Et, which provide straightforward access to various compounds with −SCF 2 CO 2 R moieties. Despite this notable progress, it is still highly desirable to develop practical and efficient reagents to the end.…”