Process for trapping thiocarbonyl fluoride

Abstract

The present invention relates to a process for trapping SCF2 comprising the following steps: - a step of reacting a compound A-SCF3 with a nucleophile, in the presence of a metallic complex comprising nickel, palladium or rhodium (I), a ligand, and a solvent, A being selected from the group consisting of: (C6-C10)aryl groups, heteroaryl groups, and a vinyl compound, said step leading to the formation of a compound AH or a compound AZ and SCF2, wherein Z is a hydrocarbon group, optionally including at least one heteroatom such as S, N or O, and / or at least one atom other than C or H, such as Se, Si, B, or P, and - a step of reacting SCF2 with a compound RH, R being a hydrocarbon group, comprising optionally at least one heteroatom, for obtaining a compound having the formula R-C(=S)-F.

Description

[0001] PROCESS FOR TRAPPING THIOCARBONYL FLUORIDE

[0002] The present invention concerns a process for trapping thiocarbonyl fluoride or analogues thereof.

[0003] In a society concerned about the environment, earth and aquatic systems pollution and circular economy, development of new technologies to meet such objectives is nowadays a real challenge and a hot topic across the whole chemical industry.

[0004] The field of organofluorine chemistry is unavoidable and fluorinated compounds are highly represented in many fields such as materials science, pharmaceutical and agrochemical industries. Indeed, the incorporation of a fluorine atom or a fluorinated unit can modify the physico-chemical properties of organic molecules in a significant way explaining the interest of the scientific community regarding this research area. However, the prevalence of these compounds raises the question of their fate and degradation. Recently, there has been a strong awareness from the scientific community and society regarding chlorofluorocarbons (CFCs), hydrofluorocarbons (HFCs) and per- and poly-fluoroalkyl substances (PFAs). It is now important to go even further and to look at the fate of emerging fluorinated groups that have become essential, such as derivatives containing a SCF3unit (eg. Toltrazuril and Fipronil).

[0005] In this context, the development of tools allowing to valorize these fluorinated derivatives, which, once used, are then considered as waste by converting them into compounds with high added value would have an undeniable ecological impact and allow for cost reduction. It is therefore essential to develop innovative tools to meet this challenge and to remove this synthetic lock.

[0006] There is currently no technology allowing to selectively cleave C(sp2)-SRf bonds on (hetero)aromatic derivatives or vinyl positions or C(sp3)-SRf bonds and any progress would have a major impact from a scientific and environmental point of view.

[0007] N. Barbero et al., Organic Letters, 2012, 14, 796-799 (Supporting Information, S1 -S78) relates to catalytic reductive cleavage of unactivated C-SMe bonds. As shown on page 797, left column, last paragraph, the SMe group, namely an electrondonating group on the sulfur atom, was reported as the most efficient in the reductive cleavage of C-S bond. The optimization process reported in Tables 1 to 6 of the supporting information (p. S3 to S5) was carried out for this specific thioether only. Table 7 (p. S5) of this document confirms that SMe group raises the highest yield with respect to cleavage of the C-S bond, while electron-attracting groups, such as Ac and C0NMe2, were inefficient.

[0008] Surprisingly, it has now been found that it was possible to selectively cleave C- S bonds and analogues of such bonds on organic molecules in the presence of an electron-attracting fluorinated group, such as CF3or analogous fluorine-containing groups.

[0009] With a view to the circular economy, which is nowadays an essential part of industrial purposes, notably through the 3R logic (Reduce, Reuse, Recycle), there is a need of reusing the fluorinated residue released in the course of the de-fluorination reaction.

[0010] One aim of the present invention is thus to provide a process for trapping a fluorinated residue, thiocarbonyl fluoride (SCF2), SCF3_or F.

[0011] The present invention relates to a process for trapping SCF2comprising the following steps:

[0012] - a step of reacting a compound having the formula (I)

[0013] A-SCF3(I) with a nucleophile, in the presence of a metallic complex comprising nickel, palladium or rhodium (I), a ligand, and a solvent,

[0014] A being selected from the group consisting of:

[0015] . (C6-Cio)aryl groups, said aryl groups being optionally substituted with at least one substituent preferably selected from the group consisting of: halogen, (Ci-Ce)alkyl, (Ci- Ce)alkoxy, -CN, -CF3, -OCF3, -NRaRt>, -SiRaRbRc, -BRaRb, (C2-C6)alkenyl, (C2-C6)alkynyl, -C(=O)-NRaRb, and -C(=O)-O(Ci-C6)alkyl;

[0016] Raand Rbbeing independently from each other H or a (Ci-Ce)alkyl group; Rcbeing a (Ci-Ce)alkyl group;

[0017] . heteroaryl groups comprising from 5 to 10 atoms and including at least one heteroatom selected from O, N, and S, said heteroaryl groups being optionally substituted with at least one substituent preferably selected from: halogen, (Ci-Ce)alkyl, (Ci-Ce)alkoxy, -CN, -CF3, -OCF3, -NRaRb, -Si(Rc)3, -BRaRb, (C2-C6)alkenyl, (C2-C6)alkynyl, -C(=O)-NRaRb, and -C(=O)-O(Ci-C6)alkyl, Ra, Rband Rcbeing as defined above; and

[0018] . a vinyl compound having the following formula (III):

[0019] R1being selected from the group consisting of: halogen, (Ci-C6)alkyl, (Ci- Ce)alkoxy, -CN, -CF3, -OCF3, -NRaRt>, -Si(Rc)3, -BRaRt>, (C2-C6)alkenyl, (C2- Ce)alkynyl, -C(=O)-NRaRb, and -C(=O)-O(Ci-C6)alkyl, Ra, Rband Rcbeing as defined above; and said step leading to the formation of a compound AH or a compound AZ and SCF2, wherein Z is a hydrocarbon group, optionally including at least one heteroatom such as S, N or O, and / or at least one atom other than C or H, such as Se, Si, B, or P, and

[0020] - a step of reacting SCF2obtained at the previous step with a compound RH, R being a hydrocarbon group, comprising optionally at least one heteroatom, for obtaining a compound having the formula R-C(=S)-F.

[0021] In particular, the present invention relates to a process for trapping SCF2comprising the following steps:

[0022] - a step of reacting a compound having the formula (I)

[0023] A-SCF3 (I) with a nucleophile, in the presence of a metallic complex comprising nickel, a ligand, and a solvent,

[0024] A being selected from the group consisting of:

[0025] . (C6-Cio)aryl groups, said aryl groups being optionally substituted with at least one substituent preferably selected from the group consisting of: halogen, (Ci-Ce)alkyl, (C1- Ce)alkoxy, -CN, -CF3, -OCF3, -NRaRb, -SiRaRbRc, -BRaRb, (C2-Ce)alkenyl, (C2-C6)alkynyl, -C(=O)-NRaRb, and -C(=O)-O(Ci-C6)alkyl;

[0026] Raand Rbbeing independently from each other H or a (Ci-Ce)alkyl group;

[0027] Rcbeing a (Ci-Ce)alkyl group;

[0028] . heteroaryl groups comprising from 5 to 10 atoms and including at least one heteroatom selected from O, N, and S, said heteroaryl groups being optionally substituted with at least one substituent preferably selected from: halogen, (Ci-Ce)alkyl, (Ci-Ce)alkoxy, -CN, -CF3, -OCF3, -NRaRb, -Si(Rc)3, -BRaRb, (C2-Ce)alkenyl, (C2-Ce)alkynyl, -C(=O)-NRaRb, and -C(=O)-O(Ci-C6)alkyl, Ra, Rband Rcbeing as defined above; and

[0029] . a vinyl compound having the following formula (III):

[0030] R1being selected from the group consisting of: halogen, (Ci-C6)alkyl, (Ci- Ce)alkoxy, -CN, -CF3, -OCF3, -NRaRt>, -Si(Rc)3, -BRaRt>, (C2-C6)alkenyl, (C2- Ce)alkynyl, -C(=O)-NRaRb, and -C(=O)-O(Ci-C6)alkyl, Ra, Rband Rcbeing as defined above; and said step leading to the formation of a compound AH and SCF2, and

[0031] - a step of reacting SCF2obtained at the previous step with a compound RH, R being a hydrocarbon group, comprising optionally at least one heteroatom, for obtaining a compound having the formula R-C(=S)-F.

[0032] The present invention provides different processes for the valorization of the fluorinated residues in situ generated during a de-fluorination reaction. Those residues might exist under different forms including XSCF3 (X being any couteranion such as Na or H), such as a HSCF3, a highly volatile gas (bp = approx. -30°C), or as a thiocarbonyl fluoride in equilibrium with a fluoride anion. The HSCF3, or thiocarbonyl fluoride / F- can be trapped for easy disposal, or can react with other compounds to afford another fluorinated molecule of interest.

[0033] The present invention also relates to a process for trapping a fluorinated residue, such as HSCF3, or the fluoride anion, comprising the following steps:

[0034] - a step of reacting a compound having the formula (I)

[0035] A-SCF3(I) with a nucleophile, in the presence of a metallic complex comprising nickel, a ligand, and a solvent,

[0036] A being as defined above, said step leading to the release of a fluorinated residue, such as HSCF3, or the fluoride anion, and

[0037] - a step of reacting said fluorinated residue, such as HSCF3, or the fluoride anion obtained at the previous step with a compound RH, R being a hydrocarbon group, comprising optionally at least one heteroatom.

[0038] The following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention herein.

[0039] The expression "Ct-Cz" means a carbon-based chain which can have from t to z carbon atoms, for example Ci-C3means a carbon-based chain which can have from 1 to 3 carbon atoms.

[0040] The term "alkyl group" means: a linear or branched, saturated, hydrocarbonbased aliphatic group comprising, unless otherwise mentioned, from 1 to 12 carbon atoms. By way of examples, mention may be made of methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, tert-butyl or pentyl groups.

[0041] The term "aryl group" means: a cyclic aromatic group comprising between 6 and 10 carbon atoms. By way of examples of aryl groups, mention may be made of phenyl or naphthyl groups.

[0042] The term "heteroaryl group" means: a 5- to 10-membered aromatic monocyclic or bicyclic group containing from 1 to 4 heteroatoms selected from O, S or N. By way of examples, mention may be made of imidazolyl, thiazolyl, oxazolyl, furanyl, thiophenyl, pyrazolyl, oxadiazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, benzofuranyl, benzothiophenyl, benzoxazolyl, benzimidazolyl, indazolyl, benzothiazolyl, isobenzothiazolyl, benzotriazolyl, quinolinyl and isoquinolinyl groups.

[0043] By way of a heteroaryl comprising 5 to 6 atoms, including 1 to 4 nitrogen atoms, mention may in particular be made of the following representative groups: pyrrolyl, pyrazolyl, 1 ,2,3-triazolyl, 1 ,2,4-triazolyl, tetrazolyl and 1 ,2,3-triazinyl.

[0044] Mention may also be made, by way of heteroaryl, of thiophenyl, oxazolyl, furazanyl, 1 ,2,4-thiadiazolyl, naphthyridinyl, quinoxalinyl, phthalazinyl, imidazo[1 ,2- a]pyridine, imidazo[2,1 -b]thiazolyl, cinnolinyl, benzofurazanyl, azaindolyl, benzimidazolyl, benzothiophenyl, thienopyridyl, thienopyrimidinyl, pyrrolopyridyl, imidazopyridyl, benzoazaindole, 1 ,2,4-triazinyl, indolizinyl, isoxazolyl, isoquinolinyl, isothiazolyl, purinyl, quinazolinyl, quinolinyl, isoquinolyl, 1 ,3,4-thiadiazolyl, thiazolyl, isothiazolyl, carbazolyl, and also the corresponding groups resulting from their fusion or from fusion with the phenyl nucleus.

[0045] When an alkyl group is substituted with an aryl group, the term "arylalkyl" or "aralkyl" group is used. The "arylalkyl" or "aralkyl" groups are aryl-alkyl- groups, the aryl and alkyl groups being as defined above. Among the arylalkyl groups, mention may in particular be made of the benzyl or phenethyl groups.

[0046] The term "halogen" means: a fluorine, a chlorine, a bromine or an iodine.

[0047] The term "alkoxy group" means: an -O-alkyl group where the alkyl group is as previously defined. By way of examples, mention may be made of -O-(Ci-C4)alkyl groups, and in particular the -O-methyl group, the -O-ethyl group, as -O-Csalkyl group, the -O-propyl group, the -O-isopropyl group, and as -O-C4alkyl group, the -O-butyl, - O-isobutyl or -O-tert-butyl group.

[0048] The term "alkynyl" as employed herein includes unsaturated, nonaromatic, hydrocarbon groups having 2 to 6 carbons, and comprising at least one triple bond. Preferably, the alkynyl group is linear. Preferably, the alkynyl group is a -(CH2)m-C=CH group, m being an integer comprised from 1 to 4.

[0049] The term "alkenyl" as employed herein includes unsaturated, nonaromatic, hydrocarbon groups having 2 to 6 carbons, and comprising at least one double bond. Preferably, the alkenyl group is linear. Preferably, the alkenyl group is a -(CH2)m- CH=CH2group, m being an integer comprised from 1 to 4.

[0050] The abovementioned "alkyl", "aryl", and "heteroaryl" groups can be substituted with one or more substituents. Among these substituents, mention may be made of the following groups: amino, hydroxyl, thiol, oxo, halogen, alkyl, alkoxy, alkylthio, alkylamino, aryloxy, arylalkoxy, cyano, trifluoromethyl, carboxy or carboxyalkyl.

[0051] The term "alkylthio" means: an -S-alkyl group, the alkyl group being as defined above.

[0052] The term "alkylamino" means: an -NH-alkyl group, the alkyl group being as defined above.

[0053] The term "aryloxy" means: an -O-aryl group, the aryl group being as defined above.

[0054] The term "arylalkoxy" means: an aryl-alkoxy- group, the aryl and alkoxy groups being as defined above.

[0055] The term "carboxyalkyl" means: an HOOC-alkyl- group, the alkyl group being as defined above. As examples of carboxyalkyl groups, mention may in particular be made of carboxymethyl or carboxyethyl. The term "haloalkyl group" means: an alkyl group as defined above, in which one or more of the hydrogen atoms is(are) replaced with a halogen atom. By way of example, mention may be made of fluoroalkyls, in particular CF3or CHF2.

[0056] The term "carboxyl" means: a COOH group.

[0057] The term "oxo" means: "=O".

[0058] In one embodiment, the compound RH is selected from the group consisting of: amines, alcohols, thiols, phosphines, phosphonates, Grignard reagents, R’Li, selenols, R’2B(OH), and R’3SiOH, R’ representing an optionally substituted alkyl, aryl, vinyl, or alkynyl group, said alkyl, aryl, and alkynyl groups being as defined above.

[0059] In one embodiment, the compound RH is selected from the group consisting of: secondary alkyl amines, anilines, alkyl alcohols, alkyl thiols, aryl thiols, aryl selenols, phosphine oxides, aryl phosphines, and Grignard reagents.

[0060] Preferably, the compound RH is selected from the group consisting of: HNRdRe, and ORf, Rdand Rebeing independently selected from the group consisting of: (Ci- Ce)alkyl groups and (C6-C )aryl groups; and Rf being a (Ci-C6)alkyl group or a (Ce- Cio)aryl(Ci-C6)alkyl group.

[0061] In one embodiment of the process according to the invention, the nucleophile is an hydride.

[0062] In one embodiment of the process according to the invention, the nucleophile is a silane compound of formula R2(R3)2SiH, R2and R3being independently from each other selected from (Ci-C6)alkyl, (Ci-C6)alkoxy, and (C6-C )aryl groups, said aryl groups being optionally substituted with at least one substituent selected from: (Ci- Cejalkyl, (Ci-C6)alkoxy, -CN, -OCF3, -NRaRt>, -Si(Rc)3, -BRaRt>, (C2-C6)alkenyl, (C2- C6)alkynyl, -C(=O)-NRaRb, -C(=O)-O(Ci-C6)alkyl, and CF3, Ra, Rband Rcbeing as defined above.

[0063] In one embodiment of the process according to the invention, the nucleophile is a silane compound of formula R2(R3)2SiH, R2and R3being independently from each other selected from (Ci-C6)alkyl, (Ci-C6)alkoxy, and (C6-C )aryl groups, said aryl groups being optionally substituted with at least one substituent selected from: (Ci- Cejalkyl, (Ci-C6)alkoxy, and -C(=O)-O(Ci-C6)alkyl, and CF3.

[0064] In one embodiment of the process according to the invention, the nucleophile is selected from the group consisting of: EtMe2SiH, Me(OMe)2SiH, Me(OEt)2SiH, (OEt)3SiH, Et3SiH, tBuMe2SiH, Me2PhSiH, Me2BnSiH, MePh2SiH, Ph3SiH, Me2(p- CF3(C6H4))SiH, Me2(p-tBu(C6H4))SiH and 1 ,1 ,3,3-tetramethyldisiloxane (TMDSO).

[0065] In one embodiment, the nucleophile is Me2(p-CF3(CeH4))SiH or Me2BnSiH, and preferably the nucleophile is Me2(p-CF3(C6H4))SiH.

[0066] In one embodiment of the process according to the invention, the nucleophile is selected from the group consisting of: alkyl amines, cycloalkyl amines, aryl amines, alkyl thiols, thiophenol compounds, aryl selenol compounds, phosphine oxides, phosphines, Grignard reagents, alcohols or esters. The alkyl amines, cycloalkyl amines and aryl amines can be primary and / or secondary amines.

[0067] In particular, the nucleophile is a ZH group, wherein Z is selected from the group consisting of: (Ci-C6)alkyl,-O-(Ci-Ci2) alkyl; heterocycloalkyl, -S-cyclo(C3-Cio)alkyl, - P(=O)-Z1Z2, and -X1-Ar1, X1-(Ci-Ci2)alkyl-Het1, where X1is S, Se, NH or N-alkyl, Ar1is an optionally substituted (Ce-Cio)aryl group, Het1is an optionally substituted heteroaryl group and Z1and Z2are, independently from each other, a (Ci-Ce)alkyl group or a (Ce-Cio)aryl group.

[0068] Preferably, Z is selected from the group consisting of: (Ci-Ce)alkyl, heterocycloalkyl, -S-cyclo(C3-Cio)alkyl, -P(=O)-Z1Z2, and -X1-Ar1, X1being S, Se or NH, and Ar1being an optionally substituted (Ce-Cio)aryl group, and Z1and Z2being, independently from each other, a (Ci-Ce)alkyl group or a (Ce-Cio)aryl group.

[0069] The terms “alkyl”, “aryl”, “heterocycloalkyl”, heteroaryl” and their optional substituents are as defined above.

[0070] More preferably, the nucleophile is selected from the group consisting of: heterocycloalkyl groups comprising at least one nitrogen and / or sulfur atom such as morpholine, aniline groups and derivatives thereof, such as 4-methylaniline, H-S-(cyclo)alkyl groups, such as CySH, H-S-aryl groups, such as 4-methylthiophenol, H-Se-aryl groups, such as benzene selenol, phosphine oxides such as HP(=O)Ph2, phosphines such as HPPh2and Grignard reagents such as Alk-MgBr, in particular iPrMgBr.

[0071] According to one embodiment, when the nucleophile is selected from the group consisting of: alkyl amines, cycloalkyl amines, aryl amines, alkyl thiols, thiophenol compounds, aryl selenol compounds, phosphine oxides, phosphines, Grignard reagents, alcohols or esters, the process of the invention as defined above can further comprise the use of a hydride compound, such as LiHMDS. In this embodiment, the compound A-SCF3of formula (I) is reacted with the nucleophile in the presence of the metallic complex, the ligand, and the solvent, and also with a hydride compound.

[0072] In this embodiment, the nucleophile is, in particular, a Grignard reactant. According to one embodiment, in the process according to the invention, the ligand is selected from the group consisting of: 1 ,5-cyclooctadiene (COD), 1 ,2- Bis(dicyclohexylphosphino)ethane (dcype), 1 ,1 ’-Bis(diphenylphosphino)ferrocene (dppf), 1 ,1 ’-Bis(di-tert-butylphosphino)ferrocene (DTBPF), 4,5-Bis(diphenyl- phosphino)-9,9-dimethylxanthene (XantPhos), triphenylarsine (AsPh3), and triphenylphosphane (PPh3).

[0073] The term “ligand” refers to a chemical component that is able to bind to the metal of the metallic complex. The initial state of a metallic complex is the state where the metallic complex is used in the reaction medium. In the initial state of the metallic complex, the ligand can be bound to the metal.

[0074] Alternatively, the ligand can be added to the reaction medium in addition to the metallic complex. In such case, the ligand will bind to the metal in the reaction medium.

[0075] According to an embodiment of the process, the ligand is bound to the metal in the initial state of the metallic complex.

[0076] According to another embodiment of the process, the ligand is added to the reaction medium in addition to the metallic complex.

[0077] According to an embodiment of the process, at least one first ligand is bound to the metal in the initial state of the metallic complex and at least one second ligand is added to the reaction medium in addition to the metallic complex, wherein the first and second ligands are identical or different.

[0078] Preferably, the metallic complex is a Ni(0) complex such as bis(1 ,5- cyclooctadiene)nickel (Ni[cod]2) or bis(triphenylphosphine)nickel (Ni[PPh3]2).

[0079] According to another embodiment, the metallic complex comprises nickel, palladium or rhodium(l). For example, the metallic complex can be a Pd(0) complex such as tris(dibenzylideneacetone)dipalladium(0) of formula Pd2dba3or tetrakis(triphenylphosphine)palladium(0) of formula Pd(PPh3)4. In particular, the metallic complex can be a Pd(ll) complex such as, for example, [1 ,3-Bis(2,6- Diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride (PEPSI Pd IPr, 905459-27-0), palladium^ I) acetate of formula Pd(OAc)2or allylpalladium(ll) chloride dimer of formula [Pd(TT-allyl)CI]2. Alternatively, the metallic complex can be a Rh(l) complex such as, for example, rhodium carbonyl chloride of formula [Rh(CO)2CI]2or a hydroxy(cyclooctadiene)rhodium(l) dimer of formula [Rh(OH)COD]2. According to one embodiment, the solvent used in the reaction of the compound of formula (I) with the nucleophile according to the invention is selected from the usual solvents used in the field. Preferably, the solvent for this step according to the invention is toluene.

[0080] According to one embodiment of the process according to the invention, the reaction of the compound of formula (I) with the nucleophile is carried out a temperature from 90°C to 140°C. Preferably, this reaction may be carried out at 90°C, 110°C, 120°C, and 140°C.

[0081] According to one embodiment, in formula (I) as defined above, A is selected from the heteroaryl groups comprising from 5 to 10 atoms and including at least one heteroatom selected from O, N, and S, said heteroaryl groups being optionally substituted with at least one substituent selected from: halogen, (Ci-Ce)alkyl, (Ci- Ce)alkoxy, -CN, -CF3, -OCF3, -NRaRt>, -Si(Rc)3, -BRaRt>, (C2-Ce)alkenyl, (C2-Ce)alkynyl, -C(=O)-NRaRb, and -C(=O)-O(Ci-C6)alkyl, Ra, Rband Rcbeing as defined above.

[0082] The present invention also relates to the process as defined above, wherein the compound of formula (I) is a compound having the following formula (1-1 ):

[0083] EXAMPLES

[0084] Example 1 : Process for trapping thiocarbonyl fluoride in the presence of secondary anilines as compound RH Ni(cod)2(10 mol%) then 21 °C, 1 h

[0085] 21, 46% ©20

[0086] Scheme 1 : Reaction conditions: Chamber A: 12 (0.5 mmol, 1 equiv.), Ni(cod)2 (10 mol%), Me2(p-CF3(C6H4))SiH (4 equiv.), toluene (0.25M), 140°C, 16 h; Chamber B: 20 (0.1 mmol), THF (0.07 M), -70°C, 16 h then 21 °C, 1 h. Yield shown is the isolated yield.

[0087] An oven-dried two-chamber tubes both equipped with a stirring bar (chamber A: 10 mL and chamber B: 2 mL) connected by a reflux condenser was filled as follow: Ni(cod)2 (14 mg, 0.05 mmol, 10 mol%), 2-((trifluoromethyl)thio)benzo[c / |thiazole 12 (1 18 mg, 0.5 mmol, 1 equiv.), Me2(p-CF3(CeH4))SiH (408 mg, 2 mmol, 4 equiv.) and toluene (2 mL) under argon for the chamber A and with secondary aniline (0.1 mmol) and THF (1.5 mL) under argon for the chamber B. The resulting solutions were stirred at 140 °C for 16 h (chamber A) and at -70 °C for 16 h then at 21 °C for 1 h (chamber B). The residue of the chamber B was concentrated under vacuum and purified by silica gel flash column chromatography to afford the desired products.

[0088] Example 2: Process for trapping thiocarbonyl fluoride in the presence of alkyl alcohols as RH

[0089] Ni(cod)2(10 mol%)

[0090] Scheme 2: Reaction conditions: Chamber A: 12 (0.5 mmol, 1 equiv.), Ni(cod)2 (10 mol%), Me2(p-CF3(CeH4))SiH (4 equiv.), toluene (0.25M), 140°C, 16 h; Chamber B: 22 (0.1 mmol), toluene (0.07 M), -70°C, 16 h then 21 °C, 1 h. Yield shown is the isolated yield.

[0091] An oven-dried two-chamber tubes both equipped with a stirring bar (chamber A: 10 mL and chamber B: 2 mL) connected by a reflux condenser was filled as follow: Ni(cod)2 (14 mg, 0.05 mmol, 10 mol%), 2-((trifluoromethyl)thio)benzo[c / |thiazole 12 (1 18 mg, 0.5 mmol, 1 equiv.), Me2(p-CF3(C6H4))SiH (408 mg, 2 mmol, 4 equiv.) and toluene (2 mL) under argon for the chamber A and with alkyl alcohol (0.1 mmol) and toluene (1 .5 mL) under argon for the chamber B. The resulting solutions were stirred at 140 °C for 16 h (chamber A) and at -70 °C for 16 h then at 21 °C for 1 h (chamber B). The residue of the chamber B was concentrated under vacuum and purified by silica gel flash column chromatography by dry loading the samples and eluting with a solvent system as noted below to afford the desired products.

[0092] Example 3: Step of reacting the compound of formula (1-1) in the presence of various nucleophiles, metallic complexes and ligands

[0093] Cat (X mol%)

[0094] Ligand (X mol%) □HMDS (X equiv.) Nucleophile (X equiv.)

[0095] Toluene, T °C, time (h) 2a

[0096] Scheme 3A Cat (X mol%) Ligand (X mol%) LiHMDS (X equiv.) Nucleophile (X equiv.) Toluene, T °C, time (h)

[0097] 12

[0098] Scheme 3B

[0099] Schemes 3A and 3B: Reaction conditions: 12 (0.5 mmol, 1 equiv.), cat (X mol%), ligand (X mol%), LiHMDS (X eq.), nucleophile (4 eq.), toluene, T(°C), Time (h), under Argon. The term “Cat” denotes the metallic complex.

[0100] An oven-dried 10 mL tube equipped with a stirring bar was charged with a metallic complex (cat, X mol%), a ligand (X mol%), LiHMDS (X eq.), 2- ((trifluoromethyl)thio)benzo[c / ]thiazole 12 (118 mg, 0.5 mmol, 1 eq.), a nucleophile (4 eq), and toluene under argon. The resulting solution was stirred at a Temperature T (°C) for 16 h or 48 h. The reaction conditions are reported in Table 1 below. The mixture was allowed to cool down to 21 °C. EtOAc (10 mL) was added in the mixture and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with EtOAc (3 x 20 mL) and the combined organic layers were dried over MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to afford the desired product 2a and 2c-2i. The corresponding yields are reported in Scheme 3C and Table 1 below.

[0101] Table 1

[0102]

[0103] Scheme 3C: Compounds 2c to 2i were synthetized according to scheme 3B in presence of a nucleophile of formula ZH.

[0104] The results show that the cleavage of the C-S bond (step leading to the formation of a compound AH and SCF2from a compound of formula (I) according to the invention) is achieved with high yields in the presence of various metallic complexes, nucleophiles and ligands. It can be expected that the process of trapping thiocarbonyl fluoride from a A-SCF3 compound using these reaction conditions will be achieved with good yields.

[0105] Example 4: Step of reacting a A-SCF3 compound, having a (C6-Ci0)aryl group as A

[0106] Ni(cod)2(5 mol%) dcype (5 mol%) morpholine (4 equiv.)

[0107] Ph-N O

[0108] LiHMDS (5 equiv.) 1 M in toluene 140 °C, 48 h, Ar 28, 12%

[0109] Scheme 4: Reaction conditions: 27 (0.5 mmol, 1 equiv.), Ni(cod)2 (5 mol%), dcype (5 mol%), LiHMDS 1 M solution in toluene (5 equiv.), morpholine (4 equiv.),

[0110] 140°C, 48 h, under Argon. Yield shown is the isolated yield.

[0111] An oven-dried 10 mL tube equipped with a stirring bar was charged with Ni(cod)2 (7 mg, 0.025 mmol, 5 mol%), dcype (11 mg, 0.025 mmol, 5 mol LiHMDS in toluene (2.5 mL, 1 M, 418 mg, 2.5 mmol, 5 equiv), 27 (0.5 mmol, 1 equiv.) and morpholine (2 mmol, 4 equiv.) under argon. The resulting solution was stirred at 140 °C for 48 h. The mixture was allowed to cool down to 21 °C. EtOAc (10 mL) was added in the mixture and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with EtOAc (3 x 20 mL) and the combined organic layers were dried over MgSO4 and concentrated under vacuum. The residue was purified by silica gel flash column chromatography to isolate the desired product 28.

[0112] This result shows that the cleavage of the C-S bond (step leading to the release of a fluorinated residue) is achieved in a presence of an aryl. It can be expected that the process of trapping thiocarbonyl fluoride from a A-SCF3compound, A being an aryl, will be achieved with good yields.

[0113] Example 5: Step of reacting a A-SCF3compound, having a vinyl group as A

[0114] Ni(cod)2(5 mol%) dcype (5 mol%) morpholine (4 equiv.) LiHMDS (5 equiv.) 1 M in toluene

[0115] 29140°C’48 h’Ar30, 38% NMR yield

[0116] Scheme 5: Reaction conditions: 29 (0.3 mmol, 1 equiv.), Ni(cod)2 (5 mol%), dcype (5 mol%), LiHMDS 1 M solution in toluene (5 equiv.), morpholine (4 equiv.), 140°C, 48 h, under Argon. Yields were determined by1H NMR using Nitromethane as an internal standard.

[0117] An oven-dried 10 mL tube equipped with a stirring bar was charged with Ni(cod)2 (4 mg, 0.015 mmol, 5 mol%), dcype (6 mg, 0.015 mmol, 5 mol%), LiHMDS in toluene (1.5 mL, 1 M, 251 mg, 1.5 mmol, 5 equiv.), 47 (0.3 mmol, 1 equiv.) and morpholine (1 .2 mmol, 4 equiv.) under argon. The resulting solution was stirred at 140 °C for 48 h. The mixture was allowed to cool down to 21 °C. EtOAc (10 mL) was added in the mixture and the resulting solution was washed with an aqueous solution of NaOH (1 M, 10 mL). The aqueous phase was extracted with EtOAc (3 x 20 mL) and the combined organic layers were dried over MgS©4 and concentrated under vacuum. The yield of 30 was determined by1H NMR using Nitromethane as an internal standard. This result shows that the cleavage of the C-S bond (step leading to the release of a fluorinated residue) is achieved in a presence of a vinyl. It can be expected that the process of trapping thiocarbonyl fluoride from a A-SCF3compound, A being an vinyl, will be achieved with good yields.

Claims

CLAIMS1 . A process for trapping SCF2comprising the following steps:- a step of reacting a compound having the formula (I)A-SCF3(I) with a nucleophile, in the presence of a metallic complex comprising nickel, palladium or rhodium (I), a ligand, and a solvent,A being selected from the group consisting of:. (C6-Cio)aryl groups, said aryl groups being optionally substituted with at least one substituent preferably selected from the group consisting of: halogen, (Ci-Ce)alkyl, (C1- Ce)alkoxy, -CN, -CF3, -OCF3, -NRaRt>, -SiRaRbRc, -BRaRb, (C2-C6)alkenyl, (C2-C6)alkynyl, -C(=O)-NRaRb, and -C(=O)-O(Ci-C6)alkyl;Raand Rbbeing independently from each other H or a (Ci-Ce)alkyl group; Rcbeing a (Ci-Ce)alkyl group;. heteroaryl groups comprising from 5 to 10 atoms and including at least one heteroatom selected from O, N, and S, said heteroaryl groups being optionally substituted with at least one substituent preferably selected from: halogen, (Ci-Ce)alkyl, (Ci-Ce)alkoxy, -CN, -CF3, -OCF3, -NRaRb, -Si(Rc)3, -BRaRb, (C2-C6)alkenyl, (C2-C6)alkynyl, -C(=O)-NRaRb, and -C(=O)-O(Ci-C6)alkyl, Ra, Rband Rcbeing as defined above; and. a vinyl compound having the following formula (III):R1being selected from the group consisting of: halogen, (Ci-Ce)alkyl, (C1- Ce)alkoxy, -CN, -CF3, -OCF3, -NRaRb, -Si(Rc)3, -BRaRb, (C2-C6)alkenyl, (C2- Ce)alkynyl, -C(=O)-NRaRb, and -C(=O)-O(Ci-C6)alkyl, Ra, Rband Rcbeing as defined above; and said step leading to the formation of a compound AH or a compound AZ, and SCF2, wherein Z is a hydrocarbon group, optionally including at least oneheteroatom such as S, N or O, and / or at least one atom other than C or H, such as Se, Si, B, or P, and- a step of reacting SCF2 with a compound RH, R being a hydrocarbon group, comprising optionally at least one heteroatom, for obtaining a compound having the formula R-C(=S)-F.

2. The process according to claim 1 comprising the following steps:- a step of reacting a compound having the formula (I)A-SCF3(I) with a nucleophile, in the presence of a metallic complex comprising nickel, a ligand, and a solvent, A being defined as in claim 1 ; and said step leading to the formation of a compound AH and SCF2, and- a step of reacting SCF2with a compound RH, R being a hydrocarbon group, comprising optionally at least one heteroatom, for obtaining a compound having the formula R-C(=S)-F.

3. The process according to claim 1 or 2, wherein the compound RH is selected from the group consisting of: amines, alcohols, thiols, phosphines, phosphonates, Grignard reagents, R’Li, selenols, R’2B(OH), and R’sSiOH, R’ representing an optionally substituted alkyl, aryl, vinyl, or alkynyl group.

4. The process according to any one of claims 1 to 3, wherein the compound RH is selected from the group consisting of: secondary alkyl amines, anilines, alkyl alcohols, alkyl thiols, aryl thiols, aryl selenols, phosphine oxides, aryl phosphines, and Grignard reagents.

5. The process according to any one of claims 1 to 4, wherein the compound RH is selected from the group consisting of: HNRdRe, and ORf, Rdand Rebeing independently selected from the group consisting of: (Ci-Ce)alkyl groups and (Ce- Cw)aryl groups; and Rf being a (Ci-Ce)alkyl group or a (C6-Cio)aryl(Ci-C6)alkyl group.

6. The process according to any one of claims 1 to 5, wherein the nucleophile is a silane compound of formula R2(R3)2SiH, R2and R3being independently from each other selected from (Ci-Ce)alkyl, (Ci-Ce)alkoxy, and (Ce- Cw)aryl groups, said aryl groups being optionally substituted with at least one substituent selected from: (Ci-Ce)alkyl, (Ci-Ce)alkoxy, -CN, -OCF3, -NRaRt>, -Si(Rc)3, -BRaRb, (C2-C6)alkenyl, (C2-C6)alkynyl, -C(=O)-NRaRb, and -C(=O)-O(Ci-C6)alkyl, and CF3, Ra, Rb and Rcbeing as defined in claim 1 .

7. The process according to any one of claims 1 to 6, wherein the nucleophile is selected from the group consisting of: EtMe2SiH, Me(OMe)2SiH, Me(OEt)2SiH, (OEt)3SiH, Et3SiH, tBuMe2SiH, Me2PhSiH, Me2BnSiH, MePh2SiH, Ph3SiH, Me2(p-CF3(C6H4))SiH, and Me2(p-tBu(C6H4))SiH.

8. The process according to any one of claims 1 to 7, wherein the nucleophile is Me2(p-CF3(CeH4))SiH or Me2BnSiH.

9. The process according to any one of claims 1 to 8, wherein the nucleophile is Me2(p-CF3(CeH4))SiH.

10. The process according to any one of claim 1 to 5, wherein the nucleophile is selected from the group consisting of: alkyl amines, cycloalkyl amines, aryl amines, alkyl thiols, thiophenol compounds, aryl selenol compounds, phosphine oxides, phosphines, Grignard reagents, alcohols and esters.

11. The process according to claim 10, wherein the nucleophile is a ZH group, wherein Z is selected from the group consisting of: (Ci-Ce)alkyl, ,-O-(Ci-Ci2) alkyl, heterocycloalkyl, -S-cyclo(C3-Ci0)alkyl, -P(=O)-Z1Z2, and -X1-Ar1, X1-(Ci-Ci2)alkyl- Het1, where X1is S, Se, NH or N-alkyl, Ar1being an optionally substituted (Ce-Cio)aryl group, Het1is an optionally substituted heteroaryl group and Z1and Z2are, independently from each other, a (Ci-Ce)alkyl group or a (Ce-Cio)aryl group.

12. The process according to claim 10 or 1 1 , further comprising the use of a hydride compound, such as LiHMDS.

13. The process according to any one of claims 1 to 12, wherein the ligand is selected from the group consisting of: 1 ,5-cyclooctadiene (COD), 1 ,2- Bis(dicyclohexylphosphino)ethane (dcype), 1 ,1 ’-Bis(diphenylphosphino)ferrocene (dppf), 1 ,1 ’-Bis(di-tert-butylphosphino)ferrocene (DTBPF), 4,5-Bis(diphenyl- phosphino)-9,9-dimethylxanthene (XantPhos), triphenylarsine (AsPh3), and triphenylphosphane (PPh3).

14. The process according to any one of claims 1 to 13, wherein the ligand is bound to the metal in the initial state of the metallic complex and / or the ligand is added to a reaction medium in addition to the metallic complex.

15. The process according to any one of claims 1 to 14, wherein the solvent is toluene.

16. The process according to any one of claims 1 to 15, wherein the reaction of the compound of formula (I) with a hydride is carried out at a temperature from 90°C to 140°C.

17. The process according to any one of claims 1 to 16, wherein the metallic complex is a Ni(0) complex such as bis(1 ,5-cyclooctadiene)nickel.

18. The process according to any one of claims 1 to 17, wherein A is selected from the heteroaryl groups comprising from 5 to 10 atoms and including at least one heteroatom selected from O, N, and S, said heteroaryl groups being optionally substituted with at least one substituent selected from: halogen, (Ci-Ce)alkyl, (Ci- Ce)alkoxy, -CN, -CF3, -OCF3, -NRaRt>, -Si(Rc)3, -BRaRt>, (C2-Ce)alkenyl, (C2-Ce)alkynyl, -C(=O)-NRaRb, and -C(=O)-O(Ci-C6)alkyl, Ra, Rband Rcbeing as defined in claim 1.

19. The process according to any one of claims 1 to 18, wherein the compound of formula (I) is a compound having the following formula (1-1 ):

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