Dimethyl(methylthio)sulfonium Tetrafluoroborate1

[5799-67-7]  · C3H9BF4S2  · Dimethyl(methylthio)sulfonium Tetrafluoroborate  · (MW 196.07)

(electrophilic sulfenylation reagent capable of reacting with nucleophilic atoms;2 reacts with electron-rich alkenes to promote addition reactions,3 cyclizations;4 activates dithioacetals,5 trithioorthoesters,6 and thioglycosides7 for carbon-carbon or carbon-heteroatom bond forming reactions)

Alternate Name: DMTSF.

Physical Data: mp 89-92 °C.

Solubility: sol MeCN, MeNO2; insol in ether, pet ether; reacts with H2O and other protic solvents.

Form Supplied in: cream-colored to white solid; available from various suppliers.

Preparative Method: DMTSF can be conveniently prepared from Dimethyl Disulfide and Trimethyloxonium Tetrafluoroborate (Me3O+ BF4-) in MeCN.8 Precipitation of the product results after addition of ether and isolation requires filtration under anhydrous conditions.

Handling, Storage, and Precautions: DMTSF must be stored under anhydrous conditions, preferably in a well sealed bottle under nitrogen. Exposure to moisture results in a stench and the reagent is corrosive. Use in a fume hood.

Methylsulfenylation of Nucleophilic Atoms.

DMTSF reacts with Potassium Cyanide to yield MeSCN and with Phenylmagnesium Bromide to yield thioanisole.8 Extensive investigations addressed the reactivity of DMTSF with nucleophilic agents.9 DMTSF does not react with phenol at rt, but reacts slowly at 60 °C to yield the methylthiophenols (ortho/para = 0.22). The reaction with anisole also requires a temperature of 60 °C and results in p-methylthioanisole and p-methylthiophenol, a consequence of ether cleavage under the reaction conditions. Unlike phenol, dimethylaniline reacts rapidly with DMTSF at rt, yielding p-methylthio-N,N-dimethylaniline in 60% yield (eq 1). Despite the presence of an electron-withdrawing group, p-nitro-N,N-dimethylaniline also reacts rapidly with DMTSF to yield p-nitro-N,N-dimethyl-N-methylthioanilinium tetrafluoroborate.

DMTSF reacts rapidly at rt with pyridine to yield the hydrolytically unstable methylthiopyridinium ion, which failed to methylate the MeSMe byproduct. When 4-cyanopyridine was used, an equilibrium mixture was detected by NMR.

Triphenyl Phosphite reacts rapidly with DMTSF at rt to yield the methylthiophosphonium salt which, unlike the pyridinium analog, methylates the MeSMe byproduct to yield Me3S+ BF4-. This salt is removed by precipitation with ether and chromatography provides triphenyl thionophosphate in an 86% yield (eq 2). This technique complements other methods of thionophosphate synthesis from phosphites.10

Synthesis of mixed disulfides involving a methylthio unit may utilize DMTSF. Thiols and thiolates react rapidly with the reagent to yield mixed disulfides. Unfortunately, disproportionation occurs, resulting in a mixture of products.9 Subsequent investigations suggest that the addition of a sterically hindered base (eq 3),11 or the use of a 2-(trimethylsilyl)ethanethiol derived component (eq 4),12 permit high yields of unsymmetrical disulfides.

In systems having a tertiary amine and a sulfide unit, DMTSF demonstrates a chemoselectivity for sulfur (eq 5).13

Allylic sulfides react with DMTSF chemoselectively at the sulfur atom, generating thiosulfonium ions. This ion formation is reversible and the allylic thiosulfonium ion is capable of a [2,3]-sigmatropic rearrangement before subsequent electrophilic addition to the alkene.14

Methylsulfenylation of Alkenes.

A key application of DMTSF in organic synthesis involves electrophilic addition to alkenes and subsequent addition of a nucleophile to the bridged sulfonium ion. Support for this mechanism is provided by the anti addition products observed.15

Carbon Nucleophiles.

Most nucleophilic carbon sources are too basic for application to these reaction conditions. Alkynylalane ate complexes demonstrate an exception (eq 6).16

Nitrogen Nucleophiles.

Nitrogen nucleophiles, specifically NH3, amines, azide, and nitrite, resulted in high yields of alkene addition products (eq 7).15a In the absence of additional nucleophiles, the resulting sulfonium salt reacted with a tertiary amine to yield the demethylated product or the ammonium salt with a retention of configuration (eq 8).15b

Oxygen Nucleophiles.

Successful application of oxygen nucleophiles includes anhydrous KOAc (anti-Markovnikov product), H2O/CaCO3 (Markovnikov product), and DMSO which, upon treatment with Diisopropylethylamine, yields a-methyl thioketones (eq 9).17

Electrophilic ring closure demonstrates another utility of DMTSF. Examples of sulfenyl etherification and sulfenyl lactonization have been reported (eq 10).18

Phosphorus Nucleophiles.

Triphenylphosphine is an effective nucleophile for reacting with the bridged sulfonium ion in high yield. The phosphonium salts generated eliminate MeSH upon reaction with base, such as 1,8-Diazabicyclo[5.4.0]undec-7-ene, resulting in a synthesis of vinylphosphonium salts. If NaOH is used, a vinylphosphine oxide is generated.19

Other Nucleophiles.

DMTSF and Et3N.3HF react with alkenes to yield products formally of a MeSF addition. Yields are in excess of 80% and the reaction proceeds rapidly.20 Homoallylic sulfides cyclized in the presence of DMTSF. The resulting sulfonium salt was successfully demethylated with Me3N to yield 3-methylthiotetrahydrothiophenes.21

Dithioacetal, Trithioorthoester, and Thioglycoside Activation.

DMTSF provides a chemoselective reagent for dithioacetal activation in the presence of electron-rich alkenes.22 This bond-forming procedure complements the TiCl4 mediated reaction between acetals and silyl enol ethers demonstrated by Mukaiyama (see also Titanium(IV) Chloride and Trimethylsilyl Trifluoromethanesulfonate). The generation of ketone precursors through dithioacetal carbanion (acyl anion equivalents) chemistry further amplifies the significance of DMTSF activation.

Dithioacetal Activation.

DMTSF chemoselectively reacts with dithioacetals in the presence of a vinylsilane22 and in the presence of a silyl enol ether (eq 11), resulting in cyclization.23

Many carbon nucleophiles tend to be too basic for successful addition to the carbocationic center provided by DMTSF activation of dithioacetals and usually result in vinyl sulfide formation. In addition, the Me2S generated competes for the electrophilic center. Allylstannanes overcome these constraints and successfully generate new carbon-carbon bonds (eq 12).24 DMTSF activation of a thioacetal resulted in an electrophilic cyclization at the 3-position of a 3-substituted indole.25

Trithioorthoester Activation.

Electron-rich aromatic rings undergo electrophilic aromatic substitution with Tris(phenylthio)methane in the presence of DMTSF. Subsequent hydrolysis results in an aldehyde and a net electrophilic formylation.6 Intramolecular reaction between a tris(phenylthio)methane unit and an alcohol represents an approach to lactone formation which utilizes the chemoselectivity of DMTSF.26

Thioglycoside Activation.

A thioglycoside was successfully converted into a glycosyl fluoride with DMTSF.7


1. (a) Meerwein, H.; Zenner, K.-F.; Gipp, R. LA 1965, 688, 67. (b) Alternate reagent: dimethyl(thiomethyl)sulfonium 2,4,6-trinitrobenzenesulfonate: Helmkamp, G. K.; Cassey, H. N.; Olsen, B. A.; Pettitt, D. J. JOC 1965, 30, 933. (c) Review: Horito, S.; Hashimoto, H. Yuki Gosei Kagaku Kyokai Shi 1990, 48, 1028 (CA 1991, 114, 121 385k).
2. Minato, H.; Miura, T.; Kobayashi, M. CL 1975, 701.
3. Trost, B. M.; Shibata, T.; Martin, S. J. JACS 1982, 104, 3228.
4. (a) Kline, M. L.; Beutow, N.; Kim, J. K.; Caserio, M. C. JOC 1979, 44, 1904. (b) O'Malley, G. J.; Cava, M. P. TL 1985, 26, 6159.
5. Trost, B. M.; Murayama, E. JACS 1981, 103, 6529.
6. Smith, R. A. J.; Bin Manas, A. R. S 1984, 166.
7. Blomberg, L.; Norberg, T. J. Carbohydr. Chem. 1992, 11, 751.
8. Meerwein, H.; Zenner, K-F.; Gipp, R. LA 1965, 688, 67.
9. Minato, H.; Miura, T.; Kobayashi, M. CL 1975, 701.
10. (a) Lawesson's Reagent: Zabirov, N. G.; Cherkasov, R. A.; Khalikov, I. S.; Pudovik, A. N. ZOB 1986, 56, 2673 (CA 1987, 107, 236 846j). (b) Sulfur: Bruzik, K. S.; Salamonczyk, G.; Stec, W. J. JOC 1986, 51, 2368. (c) Dibenzoyl disulfide: Schönberg reaction: Kamer, P. C. J.; Roelenm H. C. P. F.; van den Elst, G. A.; van der Marel, G. A.; van Boom, J. H. TL 1989, 30, 6757. (d) Tetraethylthiuram disulfide: Vu, H.; Hirschbein, B. L. TL 1991, 32, 3005. (e) 3H-1,2-Benzodithiole-3-one 1,1-dioxide: Iyer, R. P.; Egan, W.; Regan, J. B.; Beaucage, S. L. JACS 1990, 112, 1253.
11. Dubs, P.; Stüssi, R. HCA 1976, 59, 1307.
12. Anderson, M. B.; Ranasinghe, M. G.; Palmer, J. T.; Fuchs, P. L. JOC 1988, 53, 3125.
13. Kim, J. K.; Souma, Y.; Beutow, N.; Ibbeson, C.; Caserio, M. C. JOC 1989, 54, 1714.
14. Kim, J. K.; Caserio, M. C. TL 1981, 22, 4159.
15. (a) Trost, B. M.; Shibata, T. JACS 1982, 104, 3225. (b) Caserio, M. C.; Kim, J. K. JACS 1982, 104, 3231.
16. Trost, B. M.; Martin, S. F. JACS 1984, 106, 4263.
17. Trost, B. M.; Shibata, T.; Martin, S. J. JACS 1982, 104, 3228.
18. O'Malley, G. J.; Cava, M. P. TL 1985, 26, 6159.
19. (a) Okuma, K.; Koike, T.; Yamamoto, S-i.; Yonekura, K.; Ohta, H. CL 1989, 1953. (b) Okuma, K.; Koike, T.; Yamamoto, S-i.; Takeuchi, H.; Yonekura, K.; Ono, M.; Ohta, H. BCJ 1992, 65, 2375.
20. (a) Haufe, G.; Alvernhe, G.; Anker, D.; Laurent, A.; Saluzzo, C. TL 1988, 29, 2311. (b) Haufe, G.; Alvernhe, G.; Anker, D.; Laurent, A.; Saluzzo, C. JOC 1992, 57, 714.
21. Kline, M. L.; Beutow, N.; Kim, J. K.; Caserio, M. C. JOC 1979, 44, 1904.
22. Trost, B. M.; Murayama, E. JACS 1981, 103, 6529.
23. Braish, T. F.; Saddler, J. C.; Fuchs, P. L. JOC 1988, 53, 3647.
24. Trost, B. M.; Sato, T. JACS 1985, 107, 719.
25. Amat, M.; Alvarez, M.; Bonjoch, J.; Casamitjana, N.; Gràcia, J.; Lavilla, R.; Gracía, X.; Bosch, J. TL 1990, 31, 3453.
26. Posner, G. H.; Asirvatham, E.; Hamill, T. G.; Webb, K. S. JOC 1990, 55, 2132.

Edward J. Adams

E. I. DuPont de Nemours and Co., Newark, DE, USA



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