Fluorination of sulfides

Very recently, Fuchigami et al. have found that the CF3 group also promotes the anodic fluorination of sulfides (Eq. 24) [49]. 

Sulfides are selectively fluorinated a to the sulfur atom via a reaction similar to the Pummerer rearrangement (Table 2). The fluorination wa.s originally achieved by the direct fluorination of sulfides with xenon difluoride.This reaction is proposed to occur by initial oxidative fluorination of the sulfide to give an unstable sulfur(IV) difluoride of type 1, followed by loss of hydrogen fluoride to give intermediate 2, followed by fluorine transfer to give the a-fluoro sulfide. This fluorination has also been achieved with diethylaminosulfur trifluoride (DAST) in the absence or presence of catalytic amounts of antimony(III) chloride (see Vol. ElOa, pp 421-423). ... 

Fuchigami and coworkers have proposed a Pummerer-type mechanism via the fluor-osulfonium cation for the anodic fluorination of sulfides [Eq. (14)], based on the comparative study of anodic methoxylation and fluorination of fluoroalkyl sulfides [43,45]. 

Euchigami, T., Shimojo, M., and Konno, A., Electrolytic partial fluorination of organic compounds. Part 17. Regiospecihc anodic fluorination of sulfides bearing electron-withdrawing substituents at the position a to the sulfur atom, J. Org. Chem., 60, 3459, 1995. 

Chemical fluorination of the types of compounds mentioned above was also examined using commercially available fluorinating reagents such as N-fluoropyridinium salts and EtjNSFj (DAST) as these reagents are known to be effective for fluorinations of sulfides. However, the use of these reagents did not give rise to formation of any of the desired fluorination products in most cases or to only low yields of these materials. Therefore, electrochemical fluorination is superior to the conventional chemical fluorination methodologies. 

Table 10. Anodic fluorination of sulfides having oxygen-containing heterocyclic and oxygen substituents (04JOC1276)...

T. Umemoto and G. Tomizawa, a-Fluorination of sulfides with iV-fluoropyridinium triflates. Bull,... 

The limitations of this reagent are several. It caimot be used to replace a single unactivated halogen atom with the exception of the chloromethyl ether (eq. 5) to form difluoromethyl fluoromethyl ether [461 -63-2]. It also caimot be used to replace a halogen attached to a carbon—carbon double bond. Fluorination of functional group compounds, eg, esters, sulfides, ketones, acids, and aldehydes, produces decomposition products caused by scission of the carbon chains. 

A recently discovered variant of the Wallach technique is the silver ion cata lyzed fluorination of aryl diazo sulfides in hydrogen fluonde-pyridine-toluene solvent [57] (equation 12) Electron withdrawing substituents such as acetyl give higher yields of aryl fluoride (71%) than electron donating groups (butyl 39%, methoxy, 2-14%), reductive dediazoniation competes with fluorination... 

Another way to prepare fluorinated sulfides is the photochemical alkylation of sulfides or disulfides by perfluoroalkyl iodides [69, 70, 71] (equations 62-64). Reaction of trifluoromethyl bromide with alkyl or aryl disulfides in the presence of a sulfur dioxide radical anion precursor, such as sodium hydroxymethanesulfi-nate, affords trifluoromethyl sulfides [72] (equation 65). 

Preparation of fluorine-containing sulfides has been achieved mainly by the reacuon of sulfenyl chlorides (RSCl), which may react with a vanety of nucleophiles The method is based on the electrophilicity of sulfur and on the leaving-group ability of chlorine... 

Chemistry of Organic Fluorine Compounds II Table 1. Syntheses of Sulfides... 

An oxygen bound to a trifluoromethyl group has much less effect upon its chemical shift than a chlorine substituent. Thus, the fluorines of trifluoromethyl ethers (—58 ppm) are not as deshielded as those of CF3C1 (—28ppm). Those of CF3 sulfides and selenides are deshielded... 

A linear correlation of the oxidation potentials Bp of sulfides with Taft s a values of fluoromethy] groups is obtained as shown in Fig. 1 [42]. This dearly indicates that the polar effect of the fluoroalkyl group plays a significant role in the electron-transfer step from the sulfides to anode. Namely, the oxidation potential increases linearly as the number of fluorine atoms of the fluoroalkyl group increases. However, interestingly the oxidation potential was not appreciably affected by the length of the perfluoroalkyl group (Table 4). 

When the anodic fluorination of 2-monofluoroethyl sulfide 5 is carried out in methanol containing Et3N-3HF instead of acetonitrile as a solvent, interestingly the a-methoxylated product 7 rather than the a-flourinated product 6 is obtained exclusively (Scheme 6.10) [51]. As described above, 7 is not obtained from 5 under conventional anodic methoxylation conditions. Therefore, that this novel fluoride ion promoted anodic methoxylation is remarkable. As shown... 

Fuchigami and co-workers utilized the regioselective anodic fluorination of aryl propargyl sulfides 301 for the preparation of fluorinated alkyne intermediates, which were subsequently isomerized by sodium ethoxide to furnish 1-fluoro-l-arylthioallenes 302 (Scheme 8.80) [166]. 

Anodic nucleophilic functionalization of an a-carbon turned out to be particularly efficient for the fluorination of organic sulfides. The introduction of one or two fluorine atoms at the a-carbon was reported in several papers for sulfides bearing EWGs = CN, COMe, COPh, CF3, COzEt, CONEt2, PO(OEt)2) (Scheme 18) [75-78], Two systems are mainly used as the supporting electrolyte and fluorine source at a time namely, EtsN-SHF and Etr NF. 

Anodic regioselective fluorination of a-phenylsulphenylated ethyl acetates, 1-naphthalene and 2-pyridine derivatives [80], l-aryl-3-(phenylthio)oxindoles and 2-substituted-3-oxo-4-(phenylthio)-l, 2, 3,4-tetrahydroisoquinolines [81], 2-benzo-thiazolyl and 5-chloro-2-benzothiazolyl sulfides [82], a-(phenylsulfenyl)lactams [83], as well as various heterocycles such as thiolanones, oxathiolanones, dithi-olanones, 3Fl-l,4-benzoxathian-2-ones [84] in Et3N-3HF or Etr NF- HF [n = 3,4), has been reported. 

The mngsten ore called scheehte is named after Carl Wilhelm Scheele (1742—1786), who smdied and experimented with tungsten minerals, but as with many of his other near discoveries, such as oxygen, fluorine, hydrogen sulfide, hydrogen cyanide, and manganese, he was not given credit. 

The S- and Se-(perfluoroalkyl)dibenzothiophenium salts 17-27 were synthesized according to three methods (Eq. 4) (1) fluorination of the corresponding sulfide 1-6 or 8 or selenide 11 or 12 with F2 in the presence of an acid or a Lewis acid (2) fluorination with F2, followed by treatment with an acid or a Lewis acid and (3) treatment of sulfoxide 13, 14, or 15 or selenoxide 16 with triflic anhydride (Tf20). Sulfoxides 13-15 and selenoxide 16 were prepared by oxidation of the corresponding sulfides or selenide with m-chloroperbenzoic acid. 

When heated with chlorine, bromine or iodine vapors arsenic forms the corresponding trihalides however, with fluorine, arsenic pentafluoride, AsFs is produced. With sulfur it forms mixtures of sulfides, AS2S3, AS2S2 and AS2S5 in vitreous forms and varying proportions depending on the conditions of reactions. 

D.F. Andres, U. Dietrich, E.G. Laurent, B.S. Marquet, Anodic fluorination of vinyl sulfides - synthesis of a-fluoro- -thio-a, -unsaturated carbonyl compounds. Tetrahedron 53 (1997) 647-658. 

Fluoronucleosides that have an exocyclic double bond can be prepared from a fluorosulfoxide. This latter compound is obtained by electrophilic fluorination of the corresponding sulfide with Selectfluor (F-TEDA-BF4) (Figure 6.12). ... 

The fluorination of alkyl and aryl isothiocyanates with iodine pentafluoride in pyridine solution affords bis[alkyl(or aryl)trifluoromethylamino] sulfides.137 Aromatic isothioeyanates react in a few minutes at 75-90 C. more readily than their alkyl counterparts. 

Some interesting aspects of the mechanism of the selective introduction of fluorine into sulfur-containing compounds arc discussed52 below. A sulfonium ion can be obtained by the oxidation of sulfides. 

F-Teda BF4 (6) is very effective for the fluorination of a wide variety of organic substrates steroidal enol acetates (Table 7)92 and silyl enol ethers, certain carbanions, mildly activated aromatic compounds, and sulfides bearing oc-H atoms.73,75,76,77,84,88 90 The products are obtained with good yields and regioselectivity under very mild reaction conditions (Table 8). 

Electrophilic fluorination of aryl sulfides on the sugar component of nucleosides with F-Teda BF4 (6) provides a new method for the synthesis of C2", C3" and C5" fluoronucleosides.98... 

Table 1. Fluorination of Aryl Trichloromethyl Sulfides with Antimony(III) Fluoride...

Tetrabuty lammonium dihydrogen trifluoride (TB ADTF) fluorinates organic sulfides in the presence of l,3-dibromo-5,5-dimetbylhydantoin (DBH). l-Chloro-4-(methylsulfanyl)benzene (20) is fluorinated to l-chloro-4-[(fluoromethyl)sulfanyl]benzene (21) in 90% yield.216... 

Fluoromalonates can be obtained in moderate yields by fluorination of the corresponding carbanions with xenon difluoride, dimethyl sulfide and boron trifluoride-diethyl ether complex.29... 

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