A TRIFLUOROMETHYL THIANTHRENIUM COMPOUND, PROCESS FOR PREPARING THE SAME AND THE USE THEREOF

Abstract

The present inventions refers a novel trifluoromethyl thianthrenium compound referred to as TT-CF.sub.3.sup.+X.sup.?, a process for preparing the same and the use thereof for trifluoromethylating organic compounds.

Claims

1. A thianthrene derivative of the Formula (I): ##STR00029## wherein R.sup.1 to R.sup.8 may be the same or different and are each selected from hydrogen, halogen, a C.sub.1 to Ce alkyl group, which is optionally substituted by at least one halogen, or a OC.sub.1 to C.sub.6 alkyl group, and wherein X.sup.? is an anion, selected from F.sup.?, Cl.sup.?, triflate, BF.sub.4.sup.?, SbF.sub.6.sup.?, PF.sub.6.sup.?, ClO.sub.4.sup.?, 0.5 SO.sub.4.sup.2?, or NO.sub.3.sup.?.

2. A thianthrene derivative of the Formula (I) as claimed in claim 1 wherein, in Formula (I), R.sup.1 to R.sup.8 may be the same or different and are each selected from hydrogen, Cl or F and X.sup.? is an anion as defined in claim 1.

3. A thianthrene derivative of the Formula (I) as claimed in claim 1 wherein, in Formula (I), R.sup.1 to R.sup.8 are each hydrogen, and X.sup.? is an anion as defined in claim 1.

4. A thianthrene derivative of the Formula (I) as claimed in claim 1 wherein, in Formula (I), R.sup.1 to R.sup.8 are each hydrogen, and X.sup.? is an anion selected from triflate or BF.sub.4.sup.?.

5. Process for preparing a trifluoromethyl thianthrenium compound of the Formula (I) as claimed in claim 1, comprising reacting a thianthrene derivative of the Formula (II) with a trifluoromethyl group transfer agent in an organic solvent and obtaining a thianthrenium compound of the Formula (I): ##STR00030## wherein R.sup.1 to R.sup.8 may be the same or different and are each selected from hydrogen, halogen, a C.sub.1 to C.sub.6 alkyl group, which may be substituted by at least one halogen or a OC.sub.1 to C.sub.6 alkyl group.

6. Process for preparing a trifluoromethyl thianthrenium compound of the Formula (I), according to claim 5 whereby the trifluoromethyl group transfer agent is triflic acid anhydride.

7. Process for preparing the trifluoromethyl thianthrenium compound of the Formula (I) as claimed in claim 5, which further comprises treating the obtained trifluoromethyl thianthrenium triflate with an anion exchange agent to and obtaining a (trifluoromethyl)thianthrenium compound wherein the anion is selected from F.sup.?, Cl.sup.?, BF.sub.4.sup.?, SbF.sub.6.sup.?, PF.sub.6.sup.?, ClO.sub.4.sup.?, 0.5 SO.sub.4.sup.2?, or NO.sub.3.sup.?.

8. Method of using a trifluoromethyl thianthrenium compound of the Formula (I) as claimed in claim 1 as a transfer agent for transferring a trifluoromethyl group to a hydrocarbon compound.

9. Method according to claim 8, wherein said hydrocarbon compound has an at least one alkenyl moiety or C?O moiety and/or is substituted by at least one group selected from B(OR).sub.2; SR or OR wherein R is hydrogen or C.sub.1 to C.sub.3 alkyl.

10. Method according to claim 8, wherein the hydrocarbon compound is selected from an aliphatic hydrocarbon, an aromatic hydrocarbon or a heteroaromatic hydrocarbon.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0044] The invention is further illustrated by the attached Figures and Examples. In the Figures, the respective Figure shows:

[0045] FIG. 1: Common electrophilic CF.sub.3 reagents, trifluoromethyl thianthrenium triflate (1, TT-CF.sub.3.sup.+OTf.sup.?), and typical applications of TT-CF.sub.3.sup.+OTf.sup.?;

[0046] FIG. 2: Synthesis of TT-CF.sub.3.sup.+OTf.sup.?, and reactivity studies;

[0047] FIG. 3: Radical clock control experiment; and

[0048] FIG. 4A-C: (A) Cross coupling reaction,

[0049] (B) electrophilic trifluoromethylation,

[0050] (C) radical trifluoromethylation,

[0051] (D) radical hydrotrifluoromethylation of olefins, and

[0052] (E) nucleophilic trifluoromethylation with TT-CF.sub.3.sup.+OTf.sup.?.

[0053] In more detail, the Figures illustrate as follows:

[0054] FIG. 1. Common electrophilic CF.sub.3 reagents, trifluoromethyl thianthrenium triflate (1, TT-CF.sub.3.sup.+OTf.sup.?), and typical applications of TT-CF.sub.3.sup.+OTf.sup.?.

[0055] FIG. 2. Synthesis of TT-CF.sub.3.sup.+OTf.sup.?, and reactivity studies.

[0056] (A) Synthesis of TT-CF.sub.3.sup.+OTf.sup.? including a proposed mechanism for its formation. ?H and ?G data were derived from DFT studies. The bond dissociation energy (BDE) of SS bond was represented by ?H. (B) electron paramagnetic resonance spectrum under the reaction conditions (magnetic flux density), (C) CF.sub.3 radical trapping experiments, and (D) cyclic voltammogram of thianthrene and triflic anhydride in CH.sub.3CN (E [mV] vs Cp.sub.2Fe).

[0057] FIG. 3. Radical clock control experiment

[0058] 14 was isolated and characterized as analytically pure samples. The d.r. value was determined by .sup.1H NMR.

[0059] FIG. 4A-C. (A) Cross coupling reaction, (B) electrophilic trifluoromethylation, (C) radical trifluoromethylation, (D) radical hydrotrifluoromethylation of olefins, and (E) nucleophilic trifluoromethylation with TT-CF.sub.3.sup.+OTf.sup.?.

[0060] The reaction conditions are marked in the reaction equation. All non-volatile trifluorometylation products were isolated and characterized as analytically pure samples. .sup.aYields of volatile trifluorometylation products are reported based on .sup.19F NMR integration of reaction mixtures with internal standard Ph-CF.sub.3. .sup.b3.0 equiv. Et.sub.3N were used, on account of starting hydrochloride material. .sup.cAliphatic thiol (0.30 mmol, 1.0 equiv.), TT-CF.sub.3.sup.+OTf.sup.? (1.2 equiv.), 1,1,3,3-tetramethyl-guanidine (TMG, 1.2 equiv.), CH.sub.3CN (2.0 mL c=0.15 M), r.t., 6 h. .sup.dStyrene (1.00 mmol, 1.0 equiv.), TT-CF.sub.3.sup.+OTf.sup.? (1.5 equiv.), Cs.sub.2CO.sub.3 (2.0 equiv.), 1,2-benzenedithiol (2.0 equiv.), i-butanol (1.0 mL c=0.10 M), 0? C., 30 min.

Experimental Part

[0061] All reactions were carried out under ambient atmosphere unless otherwise stated. High-resolution mass spectra were obtained using Q Exactive Plus from Thermo. Concentration under reduced pressure was performed by rotary evaporation at 23-40? C. at an appropriate pressure. Purified compounds were further dried under vacuum (10.sup.?6-10.sup.?3 bar). Yields refer to purified and spectroscopically pure compounds or mixtures of constitutional isomers. All air- and moisture-sensitive manipulations were performed using standard Schlenk- and glove-box techniques under an atmosphere of argon or dinitrogen.

Solvents

[0062] Dichloromethane, anhydrous DMSO, and anhydrous DMF were purchased from Fisher Scientific GmbH. Anhydrous 1,4-dioxane and anhydrous acetonitrile were obtained from Phoenix Solvent Drying Systems. i-Butanol was degassed by three freeze-pump-thaw cycles. All deuterated solvents were purchased from Euriso-Top.

Chromatography

[0063] Thin layer chromatography (TLC) was performed using EMD TLC silica gel 60 F.sub.254 plates pre-coated with 250 ?m thickness silica gel 60 F.sub.254 and visualized by fluorescence quenching under UV light, KMnO.sub.4 stain or vanillin-H.sub.2SO.sub.4 stain. Flash column chromatography was performed using silica gel (40-63 ?m particle size) purchased from Geduran. Preparatory high-performance liquid chromatographic separation was executed on a Shimadzu Prominence Preparative HPLC system with an YMC Pack Pro C18 HPLC column.

Spectroscopy and Instruments

[0064] NMR spectra were recorded on a Bruker Ascend? 500 spectrometer operating at 500 MHZ, 471 MHz, and 126 MHz, for .sup.1H, .sup.19F, and .sup.13C acquisitions, respectively, or on a Bruker Ascend? 300 spectrometer operating at 300 MHZ, 282 MHZ, and 75 MHZ, for .sup.1H, .sup.19F, and .sup.13C acquisitions, respectively. Chemical shifts are reported in ppm with the solvent residual peak as the internal standard..sup.1 For .sup.1H NMR: CDCl.sub.3, ? 7.26; CD.sub.3OD, ? 3.31; (CD.sub.3).sub.2SO, ? 2.50; CD.sub.3CN, ? 1.94, CD.sub.2Cl.sub.2, ? 5.32. For .sup.13C NMR: CDCl.sub.3, ? 77.16; CD.sub.3OD, ? 49.00; (CD.sub.3).sub.2SO, ? 39.52; CD.sub.3CN, ? 1.32, CD.sub.2Cl.sub.2, ? 53.84. .sup.19F NMR spectra were referenced using a unified chemical shift scale based on the .sup.1H NMR resonance of tetramethylsilane (1% (v/v) solution in the respective solvent)..sup.2 Data is reported as follows: s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet, br=broad; coupling constants in Hz; integration. For cyclic voltammetry a MF-2013 electrode (99.95% Pt, 1.6 mm diameter) from Bioanalytic systems Inc. was used as working electrode.

Starting Materials

[0065] All substrates and materials were used as received from commercial suppliers, unless otherwise stated. For convenient operation, Cs.sub.2CO.sub.3 was stored in a N.sub.2-filled glovebox after being dried at 150? C. for 36 h under high-vacuum. Substrates S22,.sup.3 S23,.sup.4 S24,.sup.5 and S26.sup.3 were prepared according to published procedures.

X-Ray Crystallographic Analysis

[0066] A crystal was mounted on a nylon loop using perfluoropolyether, and transferred to a Bruker AXS Enraf-Nonius KappaCCD diffractometer (either Mok? radiation, ?=0.71073 ? or CuK? radiation, ?=1.54178 ?) equipped with an Oxford Cryosystems nitrogen flow apparatus. The sample was held at 100(2) K during the experiment. The structures were solved by the direct methods procedure and refined by invariom tool..sup.6 Non-hydrogen atoms were refined anisotropically, and hydrogen atoms were allowed to ride on the respective atoms.

S-(Trifluoromethyl)Thianthrenium Salts Synthesis

S-(Trifluoromethyl)thianthrenium triflate (1, TTCF.SUB.3..SUP.+.OTf.SUP.?.)

[0067] ##STR00003##

[0068] Under an ambient atmosphere, a 500 mL two-neck round-bottom flask equipped with a teflon-coated magnetic stirring bar, was charged with thianthrene (17.3 g, 80.0 mmol, 1.00 equiv.) and dichloromethane (200 mL, c=0.4 M). Subsequently, triflic anhydride (24.8 g, 14.8 mL, 88.0 mmol, 1.10 equiv.) was added in one portion at room temperature. Upon addition of triflic anhydride, the reaction mixture rapidly turned light purple and gradually deepened, accompanied by formation of suspended particles. The reaction mixture was stirred at 35? C. for 22 h. Subsequently, a saturated aqueous NaHCO.sub.3 solution (ca. 100 mL) was added carefully. At this point, the purple color faded away, and the suspension turned light brown. The suspension was poured into a 500 mL separatory funnel, and the aqueous layer was discarded. The organic layer (light brown solution) was concentrated to dryness under reduced pressure, resulting in the formation of light brown residue. Diethyl ether (100 mL) was added to the residue and the suspension was stirred vigorously at room temperature for 30 min. The mixture was allowed to stand for 5 min, subsequently, the solvent was decanted carefully. In order to obtain an analytically pure compound, the decanting process was repeated four times with diethyl ether. The resulting yellow slurry was concentrated to dryness under reduced pressure, accumulating to a total of 21.1 g (63%) of S-(trifluoromethyl)thianthrenium triflate (1, TTCF.sub.3.sup.+OTf.sup.?) as pale yellow solid. In most cases, S-(trifluoromethyl)thianthrenium triflate (1, TTCF.sub.3.sup.+OTf.sup.?) can be used directly in subsequent transformations without chromatographic purification or recrystallization.

[0069] S-(Trifluoromethyl)thianthrenium triflate (1, TTCF.sub.3.sup.+OTf.sup.?) can be purified by recrystallization using a mixture of DCM and n-pentane (approximately 1:1 (v:v)) or by chromatography on silica gel eluting with DCM:MeOH (30:1 (v:v)) to afford a colorless solid.

[0070] R.sub.f (DCM:MeOH, 10:1 (v:v))=0.35 (UV).

[0071] Melting point: 142-143? C. Melting process is accompanied by decomposition possibly, see Simultaneous thermal analysis section for discussion.

S-(Trifluoromethyl)thianthrenium Tetrafluoroborate (1, TTCF.SUB.3..SUP.+.BF.SUB.4..SUP.?.)

[0072] ##STR00004##

[0073] Under an ambient atmosphere, the S-(trifluoromethyl)thianthrenium triflate (1, TTCF.sub.3.sup.+OTf.sup.?, 1.30 g, 3.00 mmol) was dissolved in dichloromethane (20 mL, c=0.15 M). The dichloromethane solution was washed with aqueous NaBF.sub.4 solution (c=10% (w/v), 4?20 mL), dried over anhydrous MgSO.sub.4, filtered, and the solvent was removed under reduced pressure. The title product (1 TTCF.sub.3.sup.+BF.sub.4.sup.?) was obtained as yellow solid (1.03 g, 92%).

[0074] R.sub.f (DCM:MeOH, 10:1 (v:v))=0.35 (UV).

Trifluoromethylation of Aryl Boronic Acid

4-(Trifluoromethyl)-1,1-biphenyl (3)

[0075] ##STR00005##

[0076] Under an ambient atmosphere, a 4 mL vial equipped with a teflon-coated magnetic stirring bar, was charged with 4-biphenylboronic acid (S3, 59.4 mg, 0.300 mmol, 1.00 equiv.), trifluoromethyl thianthrenium triflate (1, 261 mg, 0.600 mmol, 2.00 equiv.), Cu powder (22.9 mg, 0.360 mmol, 1.20 equiv.), and NaHCO.sub.3 (50.4 mg, 0.600 mmol, 2.00 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, dry DMSO (2 mL, c=0.15 M) was added into the vial. The vial was capped, then it was transferred out of the glovebox. The reaction mixture was stirred at 35? C. for 17 h. The reaction mixture was added into 20 mL EtOAc in a separatory funnel, then the organic phase was washed with water (3?10 mL), dried over Na.sub.2SO.sub.4, and concentrated to roughly 3 mL under reduced pressure. Silica gel (approximately 500 mg) was added, and the mixture was evaporated to dryness. The residue was purified by column chromatography on silica gel eluting with pentane to afford 41.0 mg of the title compound (3) as colorless solid (62% yield). 25 Rr (pentane)=0.55 (UV).

3-(Trifluoromethyl)quinoline (4)

[0077] ##STR00006##

[0078] Under an ambient atmosphere, a 4 mL vial equipped with a teflon-coated magnetic stirring bar, was charged with quinolin-3-ylboronic acid (S4, 51.9 mg, 0.300 mmol, 1.00 equiv.), trifluoromethyl thianthrenium triflate (1, 261 mg, 0.600 mmol, 2.00 equiv.), Cu powder (22.9 mg, 0.360 mmol, 1.20 equiv.), and NaHCO.sub.3 (50.4 mg, 0.600 mmol, 2.00 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, dry DMSO (2 mL, c=0.15 M) was added into the vial. The vial was capped, then it was transferred out of the glovebox. The reaction mixture was stirred at 35? C. for 17 h. The reaction mixture was added into 20 mL EtOAc in a separatory funnel, then the organic phase was washed with water (3?10 mL), dried over Na.sub.2SO.sub.4, then filtered. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:25 (v:v)) to afford 47.9 mg of the title compound (4) as colorless solid (81% yield).

[0079] R.sub.f (EtOAc:pentane, 1:4 (v:v))=0.21 (UV).

[0080] 8.0, 6.8, 0.9 Hz, 1H).

1-Chloro-4-(trifluoromethyl)-2-((2-(trifluoromethyl)benzyl)oxy)benzene (5)

[0081] ##STR00007##

[0082] Under an ambient atmosphere, a 4 mL vial equipped with a teflon-coated magnetic stirring bar, was charged with (2-((2-chloro-5-(trifluoromethyl)phenoxy)methyl)phenyl)boronic acid (S5, 99.1 mg, 0.300 mmol, 1.00 equiv.), trifluoromethyl thianthrenium triflate (1, 261 mg, 0.600 mmol, 2.00 equiv.), Cu powder (22.9 mg, 0.360 mmol, 1.20 equiv.), and NaHCO.sub.3 (50.4 mg, 0.600 mmol, 2.00 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, dry DMSO (2 mL, c=0.15 M) was added into the vial. The vial was capped, then it was and transferred out from the glovebox. The reaction mixture was stirred at 35? C. for 17 h. The reaction mixture was added into 20 mL EtOAc in a separatory funnel, then the organic phase was washed with water (3?10 mL), dried over Na.sub.2SO.sub.4, and concentrated to roughly 3 mL under reduced pressure. Silica gel (approximately 500 mg) was added, and the mixture was evaporated to dryness. The residue was purified by column chromatography on silica gel eluting with pentane to afford 70.1 mg of the title compound (5) as colorless solid (66% yield).

[0083] R.sub.f (pentane)=0.54 (UV).

2-(Trifluoromethyl)benzo[b]thiophene (6)

[0084] ##STR00008##

[0085] Under an ambient atmosphere, a 4 mL vial equipped with a teflon-coated magnetic stirring bar, was charged with benzo[b]thiophen-2-ylboronic acid (S6, 53.4 mg, 0.300 mmol, 1.00 equiv.), trifluoromethyl thianthrenium triflate (1, 261 mg, 0.600 mmol, 2.00 equiv.), Cu powder (22.9 mg, 0.360 mmol, 1.20 equiv.), and NaHCO.sub.3 (50.4 mg, 0.600 mmol, 2.00 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, dry DMSO (2 mL, c=0.15 M) was added into the vial. The vial was capped, then it was transferred out of the glovebox. The reaction mixture was stirred at 35? C. for 17 h. The reaction mixture was added into 20 mL EtOAc in a separatory funnel, then the organic phase was washed with water (3?10 mL), dried over Na.sub.2SO.sub.4, and concentrated to roughly 3 mL under reduced pressure. Silica gel (approximately 500 mg) was added, and the mixture was evaporated to dryness. The residue was purified by column chromatography on silica gel eluting with pentane to afford 37.0 mg of the title compound (6) as colorless solid (61% yield). 20)

[0086] R.sub.f (pentane)=0.62 (UV).

Trifluoromethylation of Caffeine

Caffeine Derivative 7

[0087] ##STR00009##

[0088] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with caffeine (S7, 0.900 mmol, 174 mg, 3.00 equiv.) and trifluoromethyl thianthrenium triflate (1, 0.300 mmol, 130 mg, 1.00 equiv.). The vial was transferred into a N.sub.2-filled glovebox. The vial was capped, then it was transferred out of the glovebox. After adding dry CH.sub.3CN (2 mL, c=0.15 M), the reaction mixture was stirred under blue LED (34 W) at room temperature for 1 h. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:15 gradient to 1:5 (v:v)) to afford 48.0 mg of the title compound (7) as colorless solid (61% yield).

[0089] R.sub.f (EtOAc:pentane, 1:3 (v:v))=0.32 (UV).

Trifluoromethylation of Aryl Aldehyde

Methyl 4-(2,2,2-trifluoro-1-hydroxyethyl)benzoate (8)

[0090] ##STR00010##

[0091] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with methyl 4-formylbenzoate (S8, 49.2 mg, 0.300 mmol, 1.00 equiv.), trifluoromethyl thianthrenium triflate (1, 391 mg, 0.900 mmol, 3.00 equiv.), and NaOTMS (101 mg, 0.900 mmol, 3.00 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently the vial was capped, then it was transferred out of the glovebox. After adding dry DMF (2 mL, c=0.15 M), the reaction mixture was stirred at ?20? C. for 19 h. EtOAc (20 mL) was added and the resulting mixture was transferred to a separating funnel. The organic phase was washed with water (3?10 mL), dried over Na.sub.2SO.sub.4, and concentrated to roughly 3 mL under reduced pressure. Silica gel (approximately 500 mg) was added, and the mixture was evaporated to dryness. The residue was purified by column chromatography on silica gel eluting with EtOAc:pentane (1:70 gradient to 1:10 (v:v)) to afford 53.4 mg of the title compound (8) as colorless solid (76% yield).

[0092] R.sub.f (EtOAc:pentane, 1:4 (v:v))=0.26 (UV).

Trifluoromethylation of Thiols

Phenyl(trifluoromethyl)sulfane (9)

[0093] ##STR00011##

[0094] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with trifluoromethyl thianthrenium triflate (1, 261 mg, 0.600 mmol, 2.00 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, dry DMF (2 mL, c=0.15 M) was added into the vial. The vial was sealed with a teflon-lined screw cap and removed from the glovebox. After adding thiophenol (S9, 33.1 mg, 30.8 ??L, 0.300 mmol, 1.00 equiv.) and Et.sub.3N (91.1 mg, 125 ?L, 0.900 mmol, 3.00 equiv.), the reaction mixture was stirred at 40? C. for 4 h. Subsequently, trifluorotoluene (43.8 mg, 40.0 ?L, 0.300 mmol, 1.00 equiv.) was added as an internal standard. The reaction mixture was diluted with CDCl.sub.3, and the yield was determined by .sup.19F NMR spectroscopy by integration of the peak at ? ?62.91 ppm of the internal standard and the peak at ? ?43.28 ppm of the product (9, 87% yield). The identity of the product was further confirmed by GC-MS analysis.

8-((Trifluoromethyl)thio)quinolone (10)

[0095] ##STR00012##

[0096] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with thiooxine hydrochloride (S10, 59.3 mg, 0.300 mmol, 1.00 equiv.) and trifluoromethyl thianthrenium triflate (1, 261 mg, 0.600 mmol, 2.00 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, dry DMF (2 mL, c=0.15 M) and Et.sub.3N (91.1 mg, 125 ?L, 0.900 mmol, 3.00 equiv.) was added into the vial. The vial was sealed with a teflon-lined screw cap and removed from the glovebox. The reaction mixture was stirred at 40? C. for 4 h. EtOAc (20 mL) was added and the resulting mixture was transferred to a separating funnel. The organic phase was washed with water (3?10 mL). The organic phase was dried over Na.sub.2SO.sub.4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:20 (v:v)) to afford 49.9 mg of the title compound (10) as colorless liquid (73% yield).

[0097] R.sub.f (EtOAc:pentane, 1:5 (v:v))=0.48 (UV).

5-Chloro-2-((trifluoromethyl)thio)benzo[d]thiazole (11)

[0098] ##STR00013##

[0099] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with 5-chloro-2-benzothiazolethiol (S11, 60.5 mg, 0.300 mmol, 1.00 equiv.) and trifluoromethyl thianthrenium triflate (1, 261 mg, 0.600 mmol, 2.00 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, dry DMF (2 mL, c=0.15 M) and Et.sub.3N (60.7 mg, 83.6 ?L, 0.600 mmol, 2.00 equiv.) were added into the vial. The vial was sealed with a teflon-lined screw cap and removed from the glovebox. The reaction mixture was stirred at 40? C. for 4 h. EtOAc (20 mL) was added and the resulting mixture was transferred to a separating funnel. The organic phase was washed with water (3?10 mL), dried over Na.sub.2SO.sub.4, and concentrated to roughly 3 mL under reduced pressure. Silica gel (approximately 500 mg) was added, and the mixture was evaporated to dryness. The residue was purified by column chromatography on silica gel eluting with pentane to afford 66.1 mg of the title compound (11) as colorless solid (82% yield).

[0100] R.sub.f (pentane)=0.18 (UV).

Methyl N-acetyl-S-(trifluoromethyl)-L-cysteinate (12)

[0101] ##STR00014##

[0102] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with methyl acetyl-L-cysteinate (S12, 53.2 mg, 0.300 mmol, 1.00 equiv.) and trifluoromethyl thianthrenium triflate (1, 156 mg, 0.360 mmol, 1.20 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, dry CH.sub.3CN (2 mL, c=0.15 M) and 1,1,3,3-tetramethylguanidin (TMG, 41.5 mg, 45.2 ?L, 0.360 mmol, 1.20 equiv.) were added into the vial. The vial was sealed with a teflon-lined screw cap and removed from the glovebox. The reaction mixture was stirred at room temperature for 4 h. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:5 gradient to 1:2 (v:v)) to afford 59.4 mg of the title compound (12) as colorless solid (80% yield).

[0103] R.sub.f (EtOAc:pentane, 1:1 (v:v))=0.24 (KMnO.sub.4).

Racecadotril Derivative 13

[0104] ##STR00015##

[0105] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with racecadotril derived thiol (S13, 103 mg, 0.300 mmol, 1.00 equiv.) and trifluoromethyl thianthrenium triflate (1, 156 mg, 0.360 mmol, 1.20 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, dry CH.sub.3CN (2 mL, c=0.15 M) and 1,1,3,3-tetramethylguanidin (TMG, 41.5 mg, 45.2 ?L, 0.360 mmol, 1.20 equiv.) were added into the vial. The vial was sealed with a teflon-lined screw cap and removed from the glovebox. The reaction mixture was stirred at room temperature for 4 h. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:15 gradient to 1:8 (v:v)) to afford 80.8 mg of the title compound (13) as colorless solid (81% yield).

[0106] R.sub.f (EtOAc:pentane, 1:2 (v:v))=0.59 (UV).

Hydrotrifluoromethylation of Olefins

Diethyl 3-methyl-4-(2,2,2-trifluoroethyl)cyclopentane-1,1-dicarboxylate (14)

[0107] ##STR00016##

[0108] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with trifluoromethyl thianthrenium triflate (1, 287 mg, 0.660 mmol, 2.20 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, Cs.sub.2CO.sub.3 (147 mg, 0.450 mmol, 1.50 equiv.) was added into the vial. The vial was capped, then it was transferred out of the glovebox. After adding dry 1,4-dioxane (2 mL, c=0.15 M), the reaction 20) mixture was stirred at 10? C. for 1 min, followed by addition of radical clock reagent (S14, 72.1 mg, 0.300 mmol, 1.00 equiv.) and 1,2-benzenedithiol (85.3 mg, 69.1 ?L, 0.600 mmol, 3.00 equiv.) with a Hamilton syringe. The reaction mixture was stirred at 10? C. for 7 h. Subsequently, the reaction mixture was filtered (0.2 ?m PTFE), and the residue was washed with DCM (0.5 mL). Silica gel (approximately 600 mg) was added into the combined transparent organic phase. Then the mixture was concentrated to dryness under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (pure pentane gradient to 1:50 (v:v)) to afford 66.6 mg of the title compound (14) as yellow liquid (72% yield). The d.r. (>20:1) value was determined by .sup.1H NMR. The configuration of the product was determined by comparing with the literature..sup.7

[0109] R.sub.f (EtOAc:pentane, 1:9 (v:v))=0.42 (KMnO.sub.4, very weak).

(3,3,3-Trifluoropropyl)benzene (15)

[0110] ##STR00017##

[0111] Under an ambient atmosphere, a 20 mL vial containing a teflon-coated magnetic stirring bar, was charged with trifluoromethyl thianthrenium triflate (1, 651 mg, 1.50 mmol, 1.50 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, Cs.sub.2CO.sub.3 (651 mg, 2.00 mmol, 2.00 equiv.) was added into the vial. The vial was capped, then it was transferred out of the glovebox. After adding dry i-butanol (10 mL, c=0.1 M), the reaction mixture was stirred at 0? C. for 2 min, followed by addition of styrene (S15, 104 mg, 115 ?L, 1.00 mmol, 1.00 equiv.) and 1,2-benzenedithiol (56.9 mg, 46.0 ?L, 0.400 mmol, 2.00 equiv.). The reaction mixture was stirred at 0? C. for 30 min. Subsequently, trifluorotoluene (292 mg, 246 ?L, 1.00 mmol, 1.00 equiv.) was added as an internal standard. The reaction mixture was diluted with CDCl.sub.3, and the yield was determined by 19F NMR spectroscopy by integration of the peak at ? ?62.91 ppm of the internal standard and the peak at ? ?66.88 (t, J=10.2 Hz) ppm of the product (15, 75% yield). The identity of the product was further confirmed by GC-MS analysis.

2-(6,6,6-Trifluorohexyl)isoindoline-1,3-dione (16)

[0112] ##STR00018##

[0113] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with phthalimide-derived olefin (S16, 43.0 mg, 0.200 mmol, 1.00 equiv.) and trifluoromethyl thianthrenium triflate (1, 191 mg, 0.440 mmol, 2.20 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, Cs.sub.2CO.sub.3 (97.7 mg, 0.300 mmol, 1.50 equiv.) was added into the vial. The vial was capped, then it was transferred out of the glovebox. After adding dry 1,4-dioxane (2 mL, c=0.1 M), the reaction mixture was stirred at 10? C. for 1 min, followed by addition of 1,2-benzenedithiol (56.9 mg, 46.0 ?L, 0.400 mmol, 2.00 equiv.). The reaction mixture was stirred at 10? C. for 7 h. Subsequently, the reaction mixture was filtered (0.2 ?m, PTFE), and the residue was washed with DCM (0.5 mL). Silica gel (approximately 500 mg) was added into the combined transparent organic phase. Then this mixture was concentrated to dryness under reduced pressure.

[0114] The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:30 (v:v) to afford 47.0 mg of the title compound (16) as yellow liquid (82% yield).

[0115] R.sub.f (EtOAc:pentane, 1:8 (v:v))=0.34 (UV).

CF.SUB.3.-(1S)-10-camphorsulfonamide (17)

[0116] ##STR00019##

[0117] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with trifluoromethyl thianthrenium triflate (1, 191 mg, 0.440 mmol, 2.20 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, Cs.sub.2CO.sub.3 (97.7 mg, 0.300 mmol, 1.50 equiv.) was added into the vial. The vial was capped, then it was transferred out of the glovebox. After adding dry 1,4-dioxane (2 mL, c=0.1 M), the reaction mixture was stirred at 10? C. for 1 min, followed by addition of (1S)-10-camphorsulfonamide derived olefin (S17, 75.1 mg, 0.200 mmol, 1.00 equiv.) and 1,2-benzenedithiol (56.9 mg, 46.0 ?L, 0.400 mmol, 2.00 equiv.) with a Hamilton syringe. The reaction mixture was stirred at 10? C. for 7 h. Subsequently, the reaction mixture was filtered (0.2 ?m, PTFE), and the residue was washed with DCM (0.5 mL). The combined solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:20 (v:v)) to afford 67.7 mg of the title compound (17) as colorless liquid (76% yield).

[0118] R.sub.f (EtOAc:pentane, 1:4 (v:v))=0.34 (UV).

CF.SUB.3.-Fmoc-L-Nle-OH Derivative 18

[0119] ##STR00020##

[0120] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with Fmoc-L-Nle-OH-ester derived olefin (S18, 78.3 mg, 0.200 mmol, 1.00 equiv.) and trifluoromethyl thianthrenium triflate (1, 191 mg, 0.440 mmol, 2.20 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, Cs.sub.2CO.sub.3 (97.7 mg, 0.300 mmol, 1.50 equiv.) was added into the vial. The vial was capped, then it was transferred out of the glovebox. After adding dry 1,4-dioxane (2 mL, c=0.1 M), the reaction mixture was stirred at 10? C. for 1 min, followed by addition of 1,2-benzenedithiol (56.9 mg, 46.0 ?L, 0.400 mmol, 2.00 equiv.) with a Hamilton syringe. The reaction mixture was stirred at 10? C. for 7 h. Subsequently, the reaction mixture was filtered (0.2 ?m, PTFE), and the residue was washed with DCM (0.5 mL). The combined solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:30 (v:v)) to afford 67.7 mg of the title compound (18) as slightly yellow solid (90% yield).

[0121] R.sub.f (EtOAc:pentane, 1:6 (v:v))=0.24 (UV).

N-(5,5,5-Trifluoropentyl)benzamide (19)

[0122] ##STR00021##

[0123] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with benzamide derived olefin (S19, 35.0 mg, 0.200 mmol, 1.00 equiv.) and trifluoromethyl thianthrenium triflate (1, 191 mg, 0.440 mmol, 2.20 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, Cs.sub.2CO.sub.3 (97.7 mg, 0.300 mmol, 1.50 equiv.) was added into the vial. The vial was capped, then it was transferred out of the glovebox. After adding dry 1,4-dioxane (2 mL, c=0.1 M), the reaction mixture was stirred at 10? C. for 1 min, followed by addition of 1,2-benzenedithiol (56.9 mg, 46.0 ?L, 0.400 mmol, 2.00 equiv.) with a Hamilton syringe. The reaction mixture was stirred at 10? C. for 7 h. Subsequently, the reaction mixture was filtered (0.2 ?m, PTFE), and the residue was washed with DCM (0.5 mL). The combined solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:30 gradient to 1:5 (v:v)) to afford 36.7 mg of the title compound (19) as colorless solid (75% yield).

[0124] R.sub.f (EtOAc:pentane, 1:2 (v:v))=0.29 (UV).

N-(4-Chloro-2-fluorophenyl)-6,6,6-trifluorohexanamide (20)

[0125] ##STR00022##

[0126] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with N-(4-chloro-2-fluorophenyl)pent-4-enamide (S20, 35.0 mg, 0.200 mmol, 1.00 equiv.) and trifluoromethyl thianthrenium triflate (1, 191 mg, 0.440 mmol, 2.20 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, Cs.sub.2CO.sub.3 (97.7 mg, 0.300 mmol, 1.50 equiv.) was added into the vial. The vial was capped, then it was transferred out of the glovebox. After adding dry 1,4-dioxane (2 mL, c=0.1 M), the reaction mixture was stirred at 10? C. for 1 min, followed by addition of 1,2-benzenedithiol (56.9 mg, 46.0 ?L, 0.400 mmol, 2.00 equiv.) with a Hamilton syringe. The reaction mixture was stirred at 10? C. for 7 h. Subsequently, the reaction mixture was filtered (0.2 ?m, PTFE), and the residue was washed with DCM (0.5 mL). The combined solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:30 gradient to 1:15 (v:v)) to afford 53.4 mg of the title compound (20) as colorless solid (90% yield).

[0127] R.sub.f (EtOAc:pentane, 1:4 (v:v))=0.39 (UV).

Rotenone Derivative 21

[0128] ##STR00023##

[0129] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with rotenone (S21, 78.9 mg, 0.200 mmol, 1.00 equiv.) and trifluoromethyl thianthrenium triflate (1, 191 mg, 0.440 mmol, 2.20 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, Cs.sub.2CO.sub.3 (97.7 mg, 0.300 mmol, 1.50 equiv.) was added into the vial. The vial was capped, then it was transferred out of the glovebox. After adding dry 1,4-dioxane (2 mL, c=0.1 M), the reaction mixture was stirred at 10? C. for 1 min, followed by addition of 1,2-benzenedithiol (56.9 mg, 46.0 ?L, 0.400 mmol, 2.00 equiv.) with a Hamilton syringe. The reaction mixture was stirred at 10? C. for 7 h, then filtered (0.2 ?m, PTFE), and the residue was washed with DCM (0.5 mL). The combined solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:15 gradient to 1:5 (v:v)) to afford 89.4 mg of the title compound (21) as yellow solid (96% yield, a pair of diastereoisomers 21a and 21b), the d.r. value (4/3) was determined by .sup.19F NMR. Further purification of 21 by preparative HPLC (YMC-Actus Pro C18 (30?150 mm: 5 ?m), CH.sub.3CN/H.sub.2O=48:52, flow rate=42.5 mL/min, 23? C.) provided 21a (retention time: 47.6 min) and 21b (retention time: 49.9 min). 21a or 21b cannot be separated under this HPLC method completely. Pure 21a and 21b were confirmed by NMR and MS. Attempts have been made to determine the absolute configuration by NMR and growing single crystals, but without success.

[0130] R.sub.f (EtOAc:pentane, 1:2 (v:v))=0.56 (UV).

Epiandrosterone Derivative 22

[0131] ##STR00024##

[0132] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with trifluoromethyl thianthrenium triflate (1, 191 mg, 0.440 mmol, 2.20 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, Cs.sub.2CO.sub.3 (97.7 mg, 0.300 mmol, 1.50 equiv.) was added into the vial. The vial was capped, then it was transferred out of the glovebox. After adding dry 1,4-dioxane (2 mL, c=0.1 M), the reaction mixture was stirred at 10? C. for 1 min, followed by addition of epiandrosterone ester derived olefin (S22, 80.1 mg, 0.200 mmol, 1.00 equiv.) and 1,2-benzenedithiol (56.9 mg, 46.0 ?L, 0.400 mmol, 2.00 equiv.) with a Hamilton syringe. The reaction mixture was stirred at 10? C. for 7 h, then filtered (0.2 ?m, PTFE), and the residue was washed with DCM (0.5 mL). The combined solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:40 gradient to 1:13 (v:v)) to afford 88.5 mg of the title compound (22) as colorless liquid (94% yield).

[0133] R.sub.f (EtOAc:pentane, 1:7 (v:v)=0.39 (Vanillin-H.sub.2SO.sub.4).

D-Glucose Derivative 23

[0134] ##STR00025##

[0135] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with D-glucose ester (S23, 77.7 mg, 0.200 mmol, 1.00 equiv.) and trifluoromethyl thianthrenium triflate (1, 191 mg, 0.440 mmol, 2.20 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, Cs.sub.2CO.sub.3 (97.7 mg, 0.300 mmol, 1.50 equiv.) was added into the vial. The vial was capped, then it was transferred out of the glovebox. After adding dry 1,4-dioxane (2 mL, c=0.1 M), the reaction mixture was stirred at 10? C. for 1 min, followed by addition of 1,2-benzenedithiol (56.9 mg, 46.0 ?L, 0.400 mmol, 2.00 equiv.) with a Hamilton syringe. The reaction mixture was stirred at 10? C. for 7 h, then filtered (0.2 ?m, PTFE), and the residue was washed with DCM (0.5 mL). The combined solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:15 gradient to 1:5 (v:v)) to afford 66.0 mg of the title compound (23) as colorless oil (72% yield).

[0136] R.sub.f (EtOAc:pentane, 1:2 (v:v))=0.35 (KMnO.sub.4).

Quinine Derivative 24

[0137] ##STR00026##

[0138] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with TMS-quinine (S24, 67.7 mg, 0.200 mmol, 1.00 equiv.) and trifluoromethyl thianthrenium triflate (1, 191 mg, 0.440 mmol, 2.20 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, Cs.sub.2CO.sub.3 (97.7 mg, 0.300 mmol, 1.50 equiv.) was added into the vial. The vial was capped, then it was transferred out of the glovebox. After adding dry 1,4-dioxane (2 mL, c=0.1 M), the reaction mixture was stirred at 10? C. for 1 min, followed by addition of 1,2-benzenedithiol (56.9 mg, 46.0 ?L, 0.400 mmol, 2.00 equiv.) with a Hamilton syringe. The reaction mixture was stirred at 10? C. for 7 h, then filtered (0.2 ?m, PTFE), and the residue was washed with DCM (0.5 mL). The combined solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of CH.sub.3OH:CH.sub.3CN (1:40 (v:v)) to afford 60.6 mg of the title compound (24) as colorless solid (61% yield).

[0139] R.sub.f (CH.sub.3OH:CH.sub.3CN, 1:9 (v:v))=0.50 (UV).

Adapalene Derivative 25

[0140] ##STR00027##

[0141] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with adapalene allyl ester (S25, 90.5 mg, 0.200 mmol, 1.00 equiv.) and trifluoromethyl thianthrenium triflate (1, 191 mg, 0.440 mmol, 2.20 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, Cs.sub.2CO.sub.3 (97.7 mg, 0.300 mmol, 1.50 equiv.) was added into the vial. The vial was capped, then it was transferred out of the glovebox. After adding dry 1,4-dioxane (2 mL, c=0.1 M), the reaction mixture was stirred at 10? C. for 1 min, followed by addition of 1,2-benzenedithiol (56.9 mg, 46.0 ?L, 0.400 mmol, 2.00 equiv.) with a Hamilton syringe. The reaction mixture was stirred at 10? C. for 7 h, then filtered (0.2 ?m, PTFE), and the residue was washed with DCM (0.5 mL). To the flask, add silica gel (approximately 500 mg), and concentrated to dryness under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:50 (v:v)) to afford 70.0 mg of the title compound (25) as colorless solid (67% yield).

[0142] R.sub.f (EtOAc:pentane, 1:9 (v:v))=0.38 (UV).

Lithocholic Acid Derivative 26

[0143] ##STR00028##

[0144] Under an ambient atmosphere, a 4 mL vial containing a teflon-coated magnetic stirring bar, was charged with trifluoromethyl thianthrenium triflate (1, 191 mg, 0.440 mmol, 2.20 equiv.). The vial was transferred into a N.sub.2-filled glovebox. Subsequently, Cs.sub.2CO.sub.3 (97.7 mg, 0.300 mmol, 1.50 equiv.) was added into the vial. The vial was capped, then it was transferred out of the glovebox. After adding dry 1,4-dioxane (2 mL, c=0.1 M), the reaction mixture was stirred at 10? C. for 1 min, followed by addition of lithocholic acid derived olefin (S26, 94.5 mg, 0.200 mmol, 1.00 equiv.) and 1,2-benzenedithiol (56.9 mg, 46.0 ?L, 0.400 mmol, 2.00 equiv.) with a Hamilton syringe. The reaction mixture was stirred at 10? C. for 7 h, then filtered (0.2 ?m, PTFE), and the residue was washed with DCM (0.5 mL). To the flask, add silica gel (approximately 500 mg), and concentrated to dryness under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a solvent mixture of EtOAc:pentane (1:40 gradient to 1:20 (v:v)) to afford 67.5 mg of the title compound (26) as yellow oil (60% yield). 30)

[0145] R.sub.f (EtOAc:pentane, 1:0 (v:v))=0.42 (vanillin-H.sub.2SO.sub.4).

[0146] As illustrated above, the inventors have established that TT-CF.sub.3.sup.+X.sup.?, in particular TT-CF.sub.3.sup.+OTf.sup.?, is a competent electrophilic trifluoromethylating reagent. For example, copper(0)-mediated cross coupling with arylboronic acids proceeds well (as illustrated in FIG. 4A), as does electrophilic trifluoromethylation of sulfides (as illustrated in FIG. 4B). As expected, TT-CF.sub.3.sup.+OTf.sup.? can also perform in radical trifluoromethylation as shown in FIG. 4C. Unlike other electrophilic trifluoromethylation reagents, the inventors have shown that TT-CF.sub.3.sup.+OTf.sup.? is useful for nucleophilic trifluoromethylation (as illustrated in FIG. 4E, left side) through umpolung with silanolate as nucleophile. The inventors explain this reactivity by formal expulsion of a trifluoromethyl anion with thianthrene oxide as side product upon addition of silanolate to the reagent to form a metastable sulfurane (as illustrated in FIG. 4E, right side).

[0147] To evaluate TT-CF.sub.3.sup.+OTf.sup.? in a transformation that has not already been disclosed with other trifluoromethylating reagents, the inventors explored the hydrotrifluoromethylation of olefins in the absence of catalyst. Hydrotrifluoro-methylation with conventional trifluoromethylating reagents is known but only with catalysts, for example photoredox catalysts..sup.20 The inventors show here that hydrotrifluoromethylation of unactivated alpha olefins can be accomplished by simply adding olefin and TT-CF.sub.3.sup.+OTf.sup.? in the presence of 1,2-benzenedithiol as hydrogen atom donor (as illustrated in FIG. 4D). The substrate scope of the hydrotrifluoromethylation and the functional group tolerance of the new reagent are large: esters, ethers, nitrogen heterocycles, and amides, as well as complex small molecules are all tolerated. Moreover, styrene derivatives, which often engage in unproductive polymerization, isomerization, and dimerization,.sup.20b, 21 are tolerated in the transformation. Based on the observed regioselectivity and radical clock cyclization product (as illustrated in FIG. 3), the inventors propose that the transformation proceeds by radical trifluoromethylation of the olefin followed by hydrogen atom abstraction of the intermediate secondary carbon radical from the hydrogen donor.

[0148] In conclusion, the inventors have developed a new trifluoromethylating reagent, trifluoromethyl thianthrenium triflate (1, TT-CF.sub.3.sup.+OTf.sup.?), which is easily accessible from commercial starting materials in a single step. The new reagent can engage in electrophilic, nucleophilic, and radical reactions, and promises to be of synthetic utility.