Synthetic Uses of Thio- and Selenoesters of Trifluoromethylated Acids. 1. Preparation of Trifluoromethyl Sulfides and Selenides

Article abstract of DOI:10.1021/jo980649a

Trifluorothioacetates (CF₃CO-S-R, from (CF₃CO)₂O and thiols) as well as trifluoromethanethio-or trifluoromethaneselenosulfonates (CF₃SO₂-Y-R; Y = S, Se; from CF₃SO₂Na, RYYR, and Br₂) can be formally decarbonylated or desulfonylated, respectively, provided that they are photolyzed at 40°C in the presence of 1 equiv of the corresponding disulfide or diselenide. Trifluoromethyl sulfides or selenides are obtained, and the added disulfide (or diselenide) is recovered after reaction. In such a way, S-(trifluoromethyl)cysteine derivatives can be obtained.

Full text of DOI:10.1021/jo980649a

J . Org. Chem. 1999, 64, 3813-3820
3813
Syn th etic Uses of Th io- a n d Selen oester s of Tr iflu or om eth yla ted
Acid s. 1. P r ep a r a tion of Tr iflu or om eth yl Su lfid es a n d Selen id es
Thierry Billard, Nicolas Roques, and Bernard R. Langlois*
Universite´ Claude Bernard-Lyon I, Laboratoire de Chimie Organique 3, associe´ au CNRS,
43 Bd du 11 Novembre 1918, 69622 Villeurbanne, France
Received April 7, 1998 (Revised Manuscript Received February 10, 1999)
Trifluorothioacetates (CF3CO-S-R, from (CF3CO)2O and thiols) as well as trifluoromethanethio-
or trifluoromethaneselenosulfonates (CF3SO2-Y-R; Y ) S, Se; from CF3SO2Na, RYYR, and Br2)
can be formally decarbonylated or desulfonylated, respectively, provided that they are photolyzed
at 40 °C in the presence of 1 equiv of the corresponding disulfide or diselenide. Trifluoromethyl
sulfides or selenides are obtained, and the added disulfide (or diselenide) is recovered after reaction.
In such a way, S-(trifluoromethyl)cysteine derivatives can be obtained.
In tr od u ction
tral” conditions (from a redox point of view), starting from
easily available reagents.
The direct introduction of a CF3 group is now emerging
as one of the major routes to trifluoromethylated com-
pounds. Apart from the use of expensive trifluoromethyl
trimethylsilane,1 which behaves as a “-CF3” equivalent,
radical trifluoromethylation constitutes the most versa-
For this purpose, we planned to homolyze, under irra-
diation, the thio- and selenoesters of triflic acid (CF3SO2-
SR and CF3SO2SeR) that we recently described.6 In such
a way, we expected to form, along with sulfenyl and
•
selenenyl radicals, triflyl radicals (CF3SO2 ). In contrast
•
tile tool for this purpose.2 Nevertheless, most of the CF3
with arylsulfonyl and alkylsulfonyl radicals, also gener-
ated by photolysis of thiosulfonates7 or selenosulfonates,8
triflyl radicals collapse very quickly into sulfur dioxide
and trifluoromethyl radicals.5,9 Thus, trifluoromethyl
sulfides (or selenides) should result from recombination
precursors are either expensive (i.e., CF3I, anhydrous
CF3COCF3), hazardous (i.e., (CF3COO)2, (CF3)2N2), toxic
(i.e., (CF3)2Hg, (CF3)2Te), not readily available (i.e.,
Umemoto’s reagents) or need to be treated under special
conditions (i.e., electrochemical oxidation of trifluoroacetic
acid).
•
of CF3 and RS• (or RSe•) during the photolysis of CF3-
SO2SR (or CF3SO2SeR). Trifluoromethyl sulfides are very
interesting because of the high hydrophobicity brought
by the CF3S moiety (Hansch parameter ΠR ) 1.44)10
which increases the bioavailability of these compounds.11
Many of them (or their oxidized derivatives) exhibit im-
portant biological responses and some are used as phar-
maceuticals,12 veterinary drugs,13 or agrochemicals.12h,14
Though very few trifluoromethyl selenides have been
described,15 they can be suspected to exhibit interesting
biological properties, too. Like trifluoromethanethiosul-
fonates, thioesters of trifluoroacetic acid were also ex-
pected to deliver trifluoromethyl sulfides by photolysis
since trifluoroacetyl radicals are known to decompose into
carbon monoxide and trifluoromethyl radicals.16 Thus,
their homolysis has also been studied.
Several years ago, we demonstrated that trifluoro-
methyl radicals can be easily generated by single-electron
reduction of bromotrifluoromethane with cheap dithio-
nite3 or by single-electron oxidation of sodium trifluo-
romethanesulfinate (CF3SO2Na)4 with aqueous tert-butyl
hydroperoxide.5 Through such processes, •CF3 is produced
either in reducing or oxidizing media. However, it would
be useful to have in hands a technique in which the
trifluoromethyl radical could be generated under “neu-
(1) (a) Surya Prakash, G. K. In Synthetic Fluorine Chemistry; Olah
G. H., Chambers R. D., Surya Prakash G. K., Ed.; J ohn Wiley & Sons:
New York, 1992; Chapter 10, p 227. (b) Olah, G. A.; Surya Prakash,
G. K.; Wang, Q.; Li, X. Y. In Encyclopedia of Reagents for Organic
Synthesis; Paquette L., Ed.; J ohn Wiley & Sons: New York, 1995; Vol.
7, p 1067. (c) Bosmans, J . P. J anssen Chim. Acta 1992, 10, 22. (d) Surya
Prakash, G. K.; Yudin, A. K. Chem. Rev. 1997, 97, 757.
(2) McClinton, M. A.; McClinton, D. A. Tetrahedron 1992, 48, 6555.
(3) (a) Clavel, J . L.; Langlois, B.; Tordeux, M.; Wakselman, C.
Phosphorus, Sulfur, Silicon Relat. Elem. 1991, 59, 129. (b) Wakselman,
C.; Tordeux, M.; Clavel, J . L.; Langlois, B. J . Chem. Soc., Chem.
Commun. 1991, 993. (c) Clavel, J . L.; Langlois, B.; Nantermet, R.;
Tordeux, M.; Wakselman, C. J . Chem. Soc., Perkin Trans. 1 1992, 3371
and Eur. Pat. (to Rhoˆne-Poulenc Agro Co.) 374,61, 1990. (d) Tordeux,
M.; Langlois, B.; Wakselman, C. J . Chem. Soc., Perkin Trans. 1 1990,
2293. (e) Wakselman, C.; Tordeux, M. J . Chem. Soc., Chem. Commun.
1987, 1701. (f) Tordeux, M.; Wakselman, C.; Langlois, B. Eur. Pat. (to
Rhoˆne-Poulenc Co.) 298,803, 1989 [Chem. Abstr. 1989, 111, 173730b].
(4) Tordeux, M.; Langlois, B.; Wakselman, C. J . Org. Chem. 1989,
54, 2452; Eur. Pat. (to Rhoˆne-Poulenc Co.) 237,446, 1987; 278,822, 1988
[Chem. Abstr. 1989, 110, 94514k]; Eur. Pat. 396,458, 1990 [Chem.
Abstr. 1991, 114, 121482q].
(5) (a) Clavel, J . L.; Langlois, B.; Laurent, E.; Roidot, N. Phosphorus,
Sulfur, Silicon & Relat. Elem. 1991, 59, 169 and Eur. Pat. (to Rhoˆne-
Poulenc Co.) 458,684, 1991. (b) Langlois, B.; Laurent, E.; Roidot, N.
Tetrahedron Lett. 1991, 32, 7525. (c) Langlois, B.; Laurent, E.; Roidot,
N. Tetrahedron Lett. 1991, 33, 1291. (d) Langlois, B.; Monte`gre, D.;
Roidot, N. J . Fluorine Chem. 1994, 68, 63.
(6) (a) Billard, T.; Langlois, B. R.; Large, S.; Anker, D.; Roidot, N.;
Roure, P. J . Org. Chem. 1996, 61, 7545. (b) Billard, T.; Langlois, B. R.
J . Fluorine Chem. 1997, 84, 63.
(7) (a) Gilbert, B. C.; Gill, B. J . Chem. Soc., Chem. Commun. 1978,
78. (b) Chatgilialoglu, C.; Gilbert, B. C.; Gill, B.; Sexton, M. D. J . Chem.
Soc., Perkin Trans. 2 1980, 1141.
(8) (a) Gancarz, R. A.; Kice, J . L. Tetrahedron Lett. 1980, 21, 4155.
(b) Gancarz, R. A.; Kice, J . L. J . Org. Chem. 1981, 46, 4899.
(9) Gonbeau, D.; Guinon, M. F.; Duplantier, S.; Ollivier, J .; Pfister-
Guillouzo, G. Chem. Phys. 1989, 135, 85.
(10) (a) Hansch, C.; Leo, A. Substituent Constants for Correlation
Analysis in Chemistry and Biology; J ohn Wiley & Sons: New York,
1979. (b) Smart, B. E. In Organofluorine Chemistry. Principles and
Commercial Applications; Banks R. E., Smart B. E., Tatlow, C., Ed.;
Plenum Press: New York, 1994; p 57. (c) Wakselman, C.; Rico, I.
Tetrahedron Lett. 1981, 22, 323. (d) Hansch, C.; Leo, A.; Ungen, S. H.;
Khim, K. H.; Nikaitani, D.; Lien, E. J . J . Med. Chem. 1973, 16, 1207.
(11) Filler, R.; Naqvi, S. M. In Biomedical Aspects of Fluorine
Chemistry; Filler R., Kobayashi Y., Ed.; Elsevier Biomedical: New
York, Kodansha Ltd.: Tokyo, 1982; p 1.
10.1021/jo980649a CCC: $18.00 © 1999 American Chemical Society
Published on Web 05/01/1999

3814 J . Org. Chem., Vol. 64, No. 11, 1999
Billard et al.
Ta ble 1. P r ep a r a tion of Th ioester s of Tr iflu or oa cetic
a n d Tr iflic Acid s
Sch em e 1. P r ep a r a tion of
Tr iflu or om eth a n eth iosu lfon a tes
CF3SO2YR (%)6
method
CF3COYR
Y
R
(%)
cpd
A
B
C
S
S
S
S
S
S
S
S
n-C8H17
c-C6H11
t-Bu
1a
1b
1c
1d
1e
1f
97
2a
2b
2c
2d
2e
2f
88 70
65 80
80
63
81
84
96
87
81
94a
0
88
90
0
CH2CH2CO2Et
CH2Ph
Ph
85 67 87
50
4-Cl-C6H4
CH2CO2Et
CH2CH(NHCOCF3)CO2Me 1i
1g
1h
2g
Resu lts a n d Discu ssion
S
Alkyl and aryl trifluorothioacetates (CF3C(O)SR) were
readily prepared from trifluoroacetic anhydride and the
corresponding thiols, in the presence of pyridine and
catalytic amounts of 4-(dimethylamino)pyridine (DMAP).
As already mentioned,6a alkyl and aryl trifluoromethaneth-
iosulfonates cannot be obtained in the same way from
triflic anhydride and thiols. According to the techniques
we recently described,6 they were prepared (as well as
their seleno analogues) either from sodium trifluo-
romethanesulfinate and sulfenyl (or selenenyl) chlorides
or from CF3SO2Na and disulfides (or diselenides) under
oxidative conditions (Scheme 1, Table 1).
Se
Ph
3
95 55 80
a
Reaction in AcOEt without pyridine and DMAP.
Sch em e 2. Ra d ica l Ch a in P r ocess
According to their UV spectra (Table 6), trifluorothio-
acetates exhibit a small absorption at 195-215 nm and
a strong one at 220-255 nm, whereas trifluoromethaneth-
iosulfonates show a strong absorption at 190-200 nm
and a less intense one at 235-245 nm. Consequently,
their photolysis was performed in quartz vessel with a
high-pressure mercury lamp (HPK 125). Dichloromethane
was chosen as solvent.
Sch em e 3. SH2 P r ocess
In preliminary experiments, 1d (CF3COSR, R ) CH2-
CH2CO2Et) and 2d (CF3SO2SR, same R) were submitted
to photolysis in refluxing dichloromethane. As expected,
they delivered ethyl 3-(trifluoromethylthio)propionate but
in 32% and 22% yields, respectively. The almost quan-
(12) (a) Banks, R. E.; Lowe, K. C. Fluorine in Medicine in the 21st
Century; Chemserve Ltd.: Manchester, 1994. (b) Zygmunt, W. A.;
Tavormina, P. A. Can. J . Microbiol. 1966, 12, 143. (c) DeMarinis, R.
M.; Bryan, W. M. J . Org. Chem. 1977, 42, 2024. (d) Voronina, T. A.;
Gordiichuk, G. N.; Andronati, S. A.; Garibova, T. L.; Zhilina, Z. I. Khim.
Farm. Zh. 1981, 15, 55. (e) Cox, R.; Smith, R. C. Arch. Biochem.
Biophys. 1969, 129, 615. (f) Colombani, E.; Cherest, H.; De Robichon-
Szulmajster, H. J . Bacteriol. 1975, 122, 375. (g) Relimpio, A.; Slebe, J .
C.; Martinez-Carrion, M. Biochem. Biophys. Res. Commun. 1975, 63,
625. (h) Becker, A. Inventory of Industrial Fluoro-Biochemicals;
Eyrolles: Paris, 1996. (i) Yale, H. L.; Sowinski, F.; Bernstein, J . J .
Am. Chem. Soc. 1957, 79, 4375. (j) Nodiff, E. A.; Lipschutz, S.; Craig,
P. N.; Gordon, M. J . Org. Chem. 1960, 25, 60.
(13) Reisdorff, J . H. et al. Ger. Offen. (to Bayer AG) 2,4,13,722, 1975.
(14) (a) Banks, R. E. Fluorine in Agriculture; Fluorine Technology
Ltd.: Manchester, 1994. (b) Walker, S. B. Fluorine Compounds as
Agrochemicals; Fluorochem Ltd.: Old Glossop (U.K.), 1990. (c) Craft,
T. S.; McBrady, J . J . J . Heterocycl. Chem. 1975, 12, 845. (d) Berkel-
hammer, G.; Kameswaran, V. Ger. Pat. (to American Cyanamid Co.)
2,7,57,66, 1979. (e) Buntain, I. G.; Hatton, L. R.; Hawkins, D. W.;
Pearson, C. J .; Roberts, D. A. Eur. Pat. (to May & Baker Ltd.) 295,-
117, 1988. (f) Roberts et al. Eur. Pat. Appl. (to Rhoˆne-Poulenc Agro
Co.) 418,16, 1991. [Chem. Abstr. 1991, 115, 29320h]. (g) Salmon, R.
Act. Int. Appl. (to Imperial Chemical Industries Ltd.) WO 93,06,089,
1993.
titative side-formation of the corresponding disulfide 4d
(RSSR) and of some chloromethyl sulfides (ClCH2SR and
Cl2CHSR resulting from CH2Cl2) confirmed the radical
•
nature of the reaction. Thus, recombination of CF3 and
RS• was not as efficient as expected. This result could be
explained by the fact that these two transient radicals
(t1/2 ) 10-3 s) were not produced in the same reaction.
Moreover, dichloromethane was not viscous enough (η30
) 0.393 cP) to favor cage phenomena, and diffusion
prevailed over recombination. In such a situation, two
processes could be invoked to explain the formation of
CF3SR out of the solvent cage: either a chain reaction
•
between CF3 and CF3COSR or CF3SO2SR (Scheme 2),
•
or a SH2 process involving the reaction of CF3 with the
disulfide resulting from the recombination of thiyl radi-
cals (Scheme 3).
According to Scheme 2, the photon should act as a
“catalyst” and the reaction rate should not be very
sensitive to the light power. However, when using a less
powerful lamp (NPK 12) or when moving the lamp away
from the reaction vessel, conversion of 1d or 2d dropped
significantly. Thus, the chain process can be ruled out
all the more so since it implies the attack of an electro-
philic trifluoromethyl radical17 upon thioesters in which
the S(II) atom is also an electrophilic site because of the
(15) (a) Yagupolskii, L. M.; Voloshchuk, V. G. Zh. Obshch. Khim.
1966, 36, 165. (b) Ibid. 1967, 37, 1543. (c) Yagupolskii, L. M.; Maletina,
I. I.; Kondratenko, N. V.; Orda, V. V. Synthesis 1978, 11, 835. (d)
Kondratenko, N. V.; Kolomeytsev, A. A.; Popov, V. I.; Yagupolskii, L.
M. Synthesis 1985, 667. (e) Ruppert, I. J . Fluorine Chem. 1985, 29,
98. (f) Umemoto, T.; Ishihara, S. Tetrahedron Lett. 1990, 31, 3579 and
J pn. Kokai Pat. 95 126245. (g) Billard, T.; Langlois, B. R. Tetrahedron
Lett. 1996, 37, 6865. (h) Billard, T.; Large, S.; Langlois, B. R.
Tetrahedron Lett. 1997, 38, 65.
(16) Kerr, J . A.; Wright, J . P. J . Chem. Soc., Faraday Trans. 1 1985,
81, 1471.

Preparation of Trifluoromethyl Sulfides and Selenides
J . Org. Chem., Vol. 64, No. 11, 1999 3815
Sch em e 4. F or m a tion of Tr iflu or om eth yl Su lfid es
a n d Disu lfid es
trifluorothioacetates. This difference reflected the rela-
tive SO2-S and CO-S bond energies. Nevertheless, the
yields of trifluoromethyl sulfides (relative to converted
thioesters) were comparable in the trifluoroacetic and
triflic series. Good results were obtained with primary
R groups, except benzylic ones (entry 8): 2e was converted
slower than other primary trifluoromethanesulfonates,
probably because of the UV absorption of the aromatic
ring (vide infra) which decreased the quantum yield, and
the yield of 5e (vs converted 2e) decreased as the reaction
progressed, indicating that this compound was either
photosensitive or decomposed through radical processes.
As far as primary aliphatic substrates are concerned,
comparison between entries 6 and 9 shows that the yield
of 5 was also dependent on the nucleophilicity of sulfur
atoms in the corresponding disulfide, as already reported.5a
When comparing secondary compounds (R ) cyclohexyl,
entries 3-5) with primary ones (R ) octyl, entries 1 and
2), it must be noted that steric hindrance influenced the
reaction in two ways. First, secondary thioesters (1b, 2b)
were converted slower than primary ones (1a , 2a ).
Second, as already reported too,5a the condensation of
•CF3 was less efficient with the secondary disulfide 4b
than with the primary one 4a , as shown from the
respective yields of 5b and 5a (vs converted 1b and 1a );
consequently, significant yields of fluoroform (6.4%)
where also detected during irradiation of a mixture of
1b and 4b. Moreover, products resulting from R′-scission
(cf. Scheme 4) were always present in a slight but
detectable amount from 1b. Extensive R′-scission pro-
cesses could be also the reason a very poor yield of
trifluoromethyl sulfide was observed from 1c (CF3COS-
t-Bu) and tert-butyl disulfide.
electron-withdrawing effect of CF3CO and CF3SO2.
Thus, the SH2 mechanism (Scheme 3) looks more suit-
able. The detection of small quantities of CF3SSR 6d (R
) CH2CH2CO2Et) argues also for the reaction of a
trifluoromethyl radical on the disulfide (Scheme 4).
Nevertheless, the SH2 process should compete with
side-reactions from the trifluoromethyl radical (dimer-
ization or abstraction of an hydrogen atom). Traces of
fluoroform were effectively detected.
According to eq 4, the formation rate of trifluoromethyl
sulfide was dependent on the concentration of disulfide;
this one increased as the reaction progressed, but was
not high enough, especially at the beginning of the
process, to compete efficiently with side-reactions. Con-
sequently, we assumed that the formation of RSCF3
should be favored by additional disulfide (with R of the
same nature as in the starting thioester). Indeed, when
illuminating a mixture of CF3COSR or CF3SO2SR (R )
CH2CH2CO2Et) and increasing quantities of the corre-
sponding disulfide RSSR (R ) CH2CH2CO2Et), the yield
of the expected trifluoromethyl sulfide increased too
(Table 2). Correlatively, chlorinated byproducts (ClCH2-
SR and Cl2CHSR) decreased, and the balance between
introduced and recovered fluorine and sulfur atoms
became more satisfying.
This photochemical reaction has been extended to the
preparation of long-chain perfluoroalkyl sulfides from the
corresponding perfluoroacyl chlorides (Scheme 6).18
Aryl trifluoromethanethiosulfonates and trifluorothio-
acetates have been also photolyzed under the same
conditions, in the presence of the corresponding disul-
fides. However, the expected aryl trifluoromethyl sulfides
were obtained in poor yields along with noticeable
amounts of trifluoromethylated byproducts and traces of
aryl dichloromethyl sulfides (Table 5).
Entries 5 to 7 in Table 2 show that, provided that at
least 1 equiv of the corresponding disulfide was present,
the photolysis of CF3COSR and CF3SO2SR looked like a
formal decarbonylation or desulfonylation process since
the added disulfide was recovered in a high yield (or even
quantitatively):
Two reasons could explain these disappointing results.
First, light absorption by aromatic nuclei lowered the
quantum yield of the photolytic process (and consequently
the conversion of 1f,g or 2f,g). Second, 5f,g were also
photosensitive, as already reported19 and confirmed by
our determinations (Table 7). In fact, when illuminated
in refluxing dichloromethane for 3.5 h, 5g was quite
completely converted (up to 90%) into the corresponding
disulfide 4g, 4-chlorophenyl dichloromethyl sulfide, and
fluoroform (16% from 19F NMR analysis). Such a high
conversion of 5g was probably favored by the tetrahedral
configuration of the sulfur atom which lowered the
conjugative stabilization.20 Table 5 also indicates the
formation of ring-trifluoromethylated disufides as byprod-
ucts. They can be explained according to our previous
studies on trifluoromethylation of aromatic disulfides5a
(Scheme 7).
These observations were in accordance with a SH2
mechanism (Scheme 5).
To bring further evidence of this mechanism, 1c (CF3-
COS-tBu) and 2a (CF3SO2SC8H17) were photolyzed in the
presence of 4d (R ) CH2CH2CO2Et): as expected from
Scheme 5, the two possible trifluoromethyl sulfides and
the three possible disulfides were present at the end of
the reaction (Table 3).
This formal decarbonylation or desulfonylation of tri-
fluoromethylated thioesters has been applied to the
preparation of other trifluoromethyl sulfides from the
corresponding disulfides and trifluorothioacetates or tri-
fluoromethanethiosulfonates. The first experiments were
performed with aliphatic substrates (Table 4).
As shown from Table 4, trifluoromethanethiosulfonates
were converted more rapidly and more extensively than
In contrast with aryl trifluorothioacetates and trifluo-
romethanethiosulfonates, phenyl trifluoromethanesele-
(17) (a) Fossey, J .; Lefort, D.; Sorba, J . Les radicaux libres en chimie
organique; Masson: Paris, 1993; p 74. (b) Motherwell, W. D.; Crich,
D. Free Radicals Chain Reaction in Organic Synthesis; Academic
Press: London, 1992; p 4. (c) Avila, D. V.; Lusztyk, J .; W. R., Dolbier,
J r. J . Am. Chem. Soc. 1993, 115, 1577 and 1994, 116, 99.
(18) Part of the D.E.A. dissertation of J . P. Godin (our laboratory).
(19) Harris, J . F. J . Org. Chem. 1967, 32, 2063.
(20) Shivernovskaya, O. A.; Ratovskii, G. V.; Kondratenko, N. V.;
Boiko, V. N.; Yagupolskii, L. M. Ukr. Khim. Zh. 1992, 58, 687.

3816 J . Org. Chem., Vol. 64, No. 11, 1999
Ta ble 2. P h otolysis of 1d or 2d in th e P r esen ce of 4d
Billard et al.
x
time
(min)
conv
1d or 2d (%)
recovered
4d (equiv)
recovered
CF3 (%)
recovered
RS (%)
entry
reagent
(equiv)
5d (%)
6d (%)
7d (%)
1
2
3
4
5
6
7
1d
2d
1d
1d
1d
1d
2d
0
0
75
40
80
75
105
75
93
100
97
90
79
32
22
44
50
64
64
78
0.2
4
12
39
81
0.2
0.4
1.0
2.0
1.0
0.2
0.4
0.8
1.9
1.0
trace
trace
trace
trace
0
trace
trace
trace
trace
0
47
60
85
87
78
70
77
81
91
93
80
100
40
Sch em e 5. SH2 Mech a n ism
be noted that the decarbonylation of trifluorothioacetates
avoid the use of CF3Br, which is banned now because of
its deleterious effect upon stratospheric ozone. S-Tri-
fluoromethylated derivatives of cysteine have been pre-
pared in this way, which probably allows the access to
analogous compounds from homocyteine and penicil-
lamine. Moreover, the desulfonylation technique can be
applied to the preparation of rather unknown trifluo-
romethyl selenides, the properties of which are under
study in our laboratory.
nosulfonate 3 delivered a fair yield of phenyl trifluoro-
methyl selenide 10 when irradiated in the presence of 1
equiv of diphenyl diselenide 11 (Scheme 8). This is due
to the fact that the main absorption of 10 lies at 191 nm,
rather far from the wavelength needed to cleave 3 (244
nm). In this case too, 11 was recovered quite unchanged
after reaction.
Exp er im en ta l Section
Solvents were distilled prior use and stored over 3 Å
molecular sieves. Other reagents were used as received. Unless
stated otherwise, 1H, 19F, and 13C NMR spectra were recorded
in CDCl3 at 200, 188, and 50 MHz, respectively. Chemical
shifts are given in ppm relative to TMS (1H, 13C) or CFCl3 (19F)
used as internal references. Coupling constants are given in
hertz. UV absorptions were determined in acetonitrile in a 1
cm long cell, concentrations of the studied compounds lying
between 0.4 and 6.7 × 10-4 mol l-1. Mass spectrometry, using
electron impact at 70 eV, was coupled with gas chromatogra-
phy. Trifluoromethanethiosulfonates (2a -g) and phenyl tri-
fluoromethaneselenosulfonate (3) were prepared according to
our previous reports.6 Dimethyl bis(N-trifluoroacetyl)-(L)-cys-
tinate 4i was obtained according to literature procedure.21
Common spectroscopic features (UV, 19F NMR, 13C NMR) of
thio- and selenoesters of trifluoroacetic and triflic acids are
given in Table 6 and those of trifluoromethyl sulfides and
selenides are given in Table 7.
Finally, the decarbonylations of trifluorothioacetates
have been illustrated by the preparation of methyl
N-(trifluoroacetyl)-S-(trifluoromethyl)-(L)-cysteinate 5i
from suitable derivatives of (L)-cysteine 1i and (L)-cystine
4i21 (Scheme 9). Like ω,ω,ω-trifluoromethionine12e-g (which
could be also prepared by our technique from homocys-
teine and homocystine), this unatural amino acid could
exhibit original biological properties.
5i has been also prepared by photolysis of a mixture
of 4i and commercially available CF3COSEt in excess.
In this case, however, only one thiyl moiety of 4i was
consumed to deliver 5i.
Gen er a l P r oced u r e for th e P r ep a r a tion of Tr iflu o-
r oth ioa ceta tes (1a -h ). Trifluoroacetic anhydride (8 mL, 56.5
mmol), dissolved in anhydrous dichloromethane (50 mL), was
dropped, over approximately 15 min, on a solution, kept at 0
°C under nitrogen, of pyridine (4 mL, 49.5 mmol), thiol (49.5
mmol), and a few milligrams of 4-(dimethylamino)pyridine
(DMAP) in anhydrous dichloromethane (150 mL). After addi-
tion, the reaction mixture was kept at room temperature for
1 h and then brought to reflux (40 °C) for about 1 h (the
reaction was monitored by GC). After cooling, it was poured
in water (150 mL) and decanted. The aqueous phase was
extracted with dichloromethane (2 × 200 mL), and then
combined organic phases were dried over MgSO4 and evapo-
rated under vacuum at room temperature. 1a -h were ob-
tained by distillation of the crude residue. Yields are reported
in Table 1.
Con clu sion
Formal photolytic desulfonylation of trifluoromethaneth-
iosulfonates and formal photolytic decarbonylation of
trifluorothioacetates offer an easy access to valuable
trifluoromethyl sulfides, especially aliphatic ones, pro-
vided that 1 equiv of disulfide is present during irradia-
tion to act as a “collisioner”. Such techniques, performed
under “neutral” conditions (from a redox point of view),
constitute an alternative route to the trifluoromethylation
of disulfides with bromotrifluoromethane under reducing
conditions3 or with sodium trifluoromethanesulfinate
under oxidative conditions, a process in which one thiyl
moiety only delivers the expected compound.5a,d It must
Com m on Sp ectr oscop ic F ea tu r es of CF 3COSR (1a -h ).
See Table 6.
Ad d it ion a l Da t a for CF 3COSR (1a -h ). n -Oct yl Tr i-
1
flu or oth ioa ceta te (1a ). Oil. Bp20: 120 °C. H NMR: δ 3.05
(t, J ) 7.0, 2H), 1.67 (m, 2H), 1.27 (m, 10H), 0.88 (t, J )
6.6, 3H). 13C NMR: δ 31.86, 29.38, 29.18, 29.07, 28.81, 28.74,
28.73, 14.10. MS: m/z 242 (M•+), 185, 173, 145, 143, 112, 97,
69, 45.
(21) Harpp, D. N.; Gleason, J . G. J . Org. Chem. 1971, 36, 73.

Preparation of Trifluoromethyl Sulfides and Selenides
J . Org. Chem., Vol. 64, No. 11, 1999 3817
Ta ble 3. Cr oss-Cou p lin g Tr iflu or om eth yla tion
CF3SR
CF3SR′
(equiv)
recov RSSR
(equiv)a
RSSR′
R′SSR′
(equiv)
others
(equiv)
ZOn
CO
R′
(equiv)a
(equiv)a
t-Bu
0.31
(5d )
0.01b
(5c)
0.55
(4d )
0.41
0c
(4c)
CF3SSR (0.02)a
CF3SSR′ (0.13)b
CF3 on Csp2 (0.06)
SO2
R
n-C8H17
0.44
(5d )
0.25
(5a )
>0d
(4d )
>0d
>0d
(4a )
a
b
)
CH2CH2CO2Et. R′-Scission of the intermediate radical favored over R-scission when R′
)
t-Bu (Scheme 4). c For-
d
mation of 4c disfavored because of steric factors. Comparable amounts of RSSR, RSSR′, and R′SSR′ from gas-phase chroma-
tography.
Ta ble 4. P r ep a r a tion of Alip h a tic Tr iflu or om eth yl Su lfid es fr om Alip h a tic Tr iflu or om eth yla ted Th ioester s
time
(min)
conv
(%)
RSCF3 5 (%)a
vs conv 1 or 2
RSSCF3
(%)a
recov
CF3 (%)
substrate
1a
entry
R
1
2
3
4
5
6
7
8
n-C8H17
n-C8H17
c-C6H11
c-C6H11
c-C6H11
105
40
90
92
100
72
88
94
79
100
41
78
87
76
74 (80)
29 (42)
38
32 (39)
81
74 (78)
27
17
(5)
0
(2)
(7)
(11)
0
83
80
67
45
43
85
78
70
35
61
60
2a
1b
1d
2b
2b
80
150
105
40
40
80
CH2CH2CO2Et
CH2CH2CO2Et
CH2Ph
2d
2e
2e
0
(6)
(9)
(4)
CH2Ph
9
10
CH2CO2Et
CH2CH(E)NHCOCF3
(E ) CO2Me)
1h
1i
125
110
53
60
100
a
Isolated yields. In parentheses:crude yields from 19F NMR.
Sch em e 6. Syn th esis of Lon g-Ch a in P er flu or oa lk a n oic Th ioester s
Ta ble 5. F or m a tion of Ar yl Tr iflu or om eth yl Su lfid es fr om Ar yl Tr iflu or om eth yla ted Th ioester s
time
(min)
conv 1
or 2 (%)
ArSCF3 5 vs
ArSSCF3
ArCF3
recov
CF3 (%)
CF3ZOnSAr
1f
1g
entry
R
conv 1 or 2 (%)a
8 (%)a
9 (%)a
1
2
3
4
H
H
4-Cl
4-Cl
180
80
210
80
77
100
68
34
20 (25)
40
>0
(2)
>0
(7)
(10)
(10)
(3)
0
59
37
62
42
2f
2g
94
27 (31)
a
Isolated yields. In parentheses:crude yields from 19F NMR.
1
c-Hexyl Tr iflu or oth ioa ceta te (1b). Oil. Bp20: 94 °C. H
Eth yl 3-(Tr iflu or oa cetylth io)p r op ion a te (1d ). Oil.
1
NMR: δ 3.70 (m, 1H), 1.97 (m, 2H), 1.50 (m, 8H). 13C NMR:
δ 43.73, 32.51, 25.78, 25.41. MS: m/z 212 (M•+), 143, 115, 97,
83, 45.
Bp20: 101-102 °C. H NMR: δ 4.20 (q, J ) 7.2, 2H), 3.31 (t,
J ) 6.8, 2H), 2.71 (t, J ) 6.8, 2H), 1.28 (t, J ) 7.2, 3H). 13C
NMR: δ 171.01, 61.15, 33.30, 24.25, 14.04. MS: m/z 230 (M•+),
185, 157, 133, 101, 97, 87, 73, 69, 45.
ter t-Bu tyl Tr iflu or oth ioa ceta te (1c). Oil. Bp760: 99 °C.
1H NMR: δ 1.56 (s, 3H). 13C NMR: δ 50.50, 29.43. MS: m/z
186 (M•+), 171, 97, 74, 69, 57, 59, 56.
Ben zyl Tr iflu or oth ioa ceta te (1e). Oil. Bp20: 115-117 °C.
1H NMR: δ 7.80 (s, 5H), 4.24 (s, 2H). 13C NMR: δ 134.88,

3818 J . Org. Chem., Vol. 64, No. 11, 1999
Billard et al.
Ta ble 6. Sp ectr oscop ic F ea tu r es of CF 3ZOn YR:CF 3COSR (1a -j), CF 3SO2SR (2a -g), a n d CF 3SO2SeP h (3)
13C NMR
19F NMR δ (ppm)
J C-F (Hz)
CF3 (q) δ (ppm)
J C-F (Hz)
CF3CO δ (ppm)
J C-F (Hz)
CF3ZOnYC
δ (ppm)
λmax
(nm)
ꢀ (L
no.
R
ZOnY
mol-1 cm-1
)
Et (commercial)
COS
COS
243
244
7500
5200
1a
1b
1c
1d
1e
1f
1g
1h
1i
n-C8H17
-75.98
-76.04
-76.29
-76.00
-76.47
-75.50
-75.28
-75.69
-75.67
-78.96
-79.20
-78.95
-78.64
-77.60
-75.46
-77.60
115.75
290.0
115.74
291.0
115.38
292.0
118.62
290.4
115.79
290.6
116.02
291.8
115.93
291.5
115.60
290.3
115.50
289.0
119.65
327.7
119.52
327.7
119.58
327.6
119.68
327.9
120.11
330.0
120.06
330.0
118.63
332.0
184.95
40.0
184.45
36.7
189.55
38.6
185.29
40.2
184.39
40.3
183.34
39.9
183.04
40.4
183.77
41.0
31.86
43.73
50.50
24.25
33.66
123.17
121.55
31.64
30.60
37.97
53.72
34.49
41.99
124.57
122.94
125.41
c-C6H11
t-Bu
COS
COS
COS
COS
COS
COS
COS
COS
SO2S
SO2S
SO2S
SO2S
SO2S
SO2S
SO2Se
245
243
242
5010
4300
2600
CH2CH2CO2Et
CH2Ph
218
246
219
246
228
254
4750
4750
4400
2600
20000
6900
Ph
4-Cl-C6H4
CH2CO2Et
CH2CH(CO2Me)
NHCOCF3
n-C8H17
184.37
39.0
2a
2b
2d
2e
2f
2g
3
193
239
192
239
195
237
2105
105
1917
94
2812
625
c-C6H11
CH2CH2CO2Et
CH2Ph
Ph
200
238
22325
10930
4-Cl-C6H4
Ph
200
244
12217
7195
Ta ble 7. Sp ectr oscop ic F ea tu r es of CF 3YR:CF 3SR (5a -j) a n d CF 3SeP h (10)
13C NMR
19F NMR δ (ppm)
J C-F (Hz)
CF3 (q) δ (ppm)
J C-F (Hz)
CF3YC δ (ppm)
J C-F (Hz)
λmax
(nm)
ꢀ (L
no.
R
Y
mol-1 cm-1
)
5a
5b
n-C8H17
S
-41.73
-39.60
131.32
305.6
122.73
306.0
29.94
2.0
43.98
1.5
c-C6H11
S
5c
5d
t-Bu
CH2CH2CO2Et
S
S
-36.64
-41.87
130.93
306.0
24.68
2.3
5e
5f
CH2Ph
Ph
S
-42.15
-43.37
-43.35
-42.82
-41.33
-36.60
130.70
306.8
129.73
307.8
129.35
308.2
130.21
307.0
130.27
307.0
122.75
332.6
34.28
2.3
124.45
2.1
122.80
2.2
31.91
3.0
S
193
238
220
239
13375
1812
8500
3900
5g
5h
5i
4-Cl-C6H4
CH2CO2Et
S
S
CH2CH(CO2Me)
NHCOCF3
Ph
S
30.75
10
Se
122.62
1.5
191
213
260
20555
7407
741
129.09, 129.07, 128.28, 33.66. MS: m/z 220 (M•+), 151, 121,
91, 77, 69, 45.
P h en yl Tr iflu or oth ioa ceta te (1f). Oil. Bp20: 85-95 °C.
1H NMR: δ 7.45 (m 5H). 13C NMR: δ 134.61, 130.90, 129.91,
123.17. MS: m/z 206 (M•+), 137, 109, 77, 69.
P r ep a r a tion of Meth yl Bis(N,S-tr iflu or oa cetyl)-(L)-
cystein a te (1i). Trifluoroacetic anhydride (17 mL, 120 mmol)
was dropped, over approximately 35 min, on a suspension of
methyl (L)-cysteinate hydrochloride (5.13 g, 30 mmol) in ethyl
acetate (30 mL), kept at 0 °C under nitrogen. The suspension
dissolved during dropping, after which stirring was continued
at room temperature for 1 h 30 min. Ethyl acetate was then
evaporated under vacuum at 50 °C, and the white solid residue
was added to water (50 mL). The resulting aqueous phase was
extracted with dichloromethane (3 × 70 mL). The combined
organic phases were washed with a 5% aqueous solution of
NaHCO3 until pH ) 8 and then with water until neutral and
dried over MgSO4. Dichloromethane was evaporated under
4-Ch lor op h en yl Tr iflu or oth ioa ceta te (1g). Oil. Bp20
:
123-124 °C. 1H NMR: δ 7.46-7.33 (m, 5H). 13C NMR:
δ
137.66, 135.87, 130.27, 121.55. MS: m/z 242 (M•+ + 2), 240
(M•+), 171, 145, 143, 108, 99, 45.
Eth yl 2-(Tr iflu or oa cetylth io)a ceta te (1h ). Oil. Bp20: 90
1
°C. H NMR: δ 4.24 (q, J ) 7.1, 2H), 3.86 (s, 2H), 1.30 (t, J )
7.1, 3H). 13C NMR: δ 166.69, 62.64, 31.46, 14.05. MS: m/z
216 (M•+), 171, 147, 144, 143, 119, 97, 75, 69, 45.

Preparation of Trifluoromethyl Sulfides and Selenides
J . Org. Chem., Vol. 64, No. 11, 1999 3819
Sch em e 7. F or m a tion of Rin g-Tr iflu or om eth yla ted P r od u cts
Sch em e 8. P h otolysis of P h en yl Tr iflu or om eth a n eselen osu lfon a te 3
crude mixture was treated with trifluoroacetic acid (0.1 mL,
Sch em e 9. P r ep a r a tion of Meth yl
1 mmol) and then filtered on silica gel (10 g) with dichlo-
romethane as eluent. The filtrate was dried over MgSO4,
filtered, and evaporated under vacuum at room temperature
to afford 0.38 g of C7F15C(O)SCH3 (yield ) 86%). Colorless oil.
1H NMR: δ 2.49 (s, 3H). 13C NMR: δ 187.13, 107.67-120.96,
11.86. 19F NMR: δ -81.43 (t, J ) 9.9, 3F), -116.97 (t, J )
13.2, 2F), -121.87 (broad, 2F), -122.51 (broad, 4F), -123.22
(broad, 2F), -126.67 (broad, 2F). m/z 444 (M•+), 397, 75, 69,
47.
N-(Tr iflu or oa cetyl)-S-(tr iflu or om eth yl)-(L)-Cystein a te
Gen er a l P r oced u r e for th e P h otolysis of Th ioester s
of Tr iflu or oa cetic (1a ,b,d -i), Tr iflic (2a ,b,d -g), a n d P en -
ta d eca flu or oh ep ta n oic Acid s a s w ell a s for P h en yl Tr i-
flu or om eth a n eselen osu lfon a te (3). The photolysis was
performed in a cylindrical flask (Φ ) 50 mm, l ) 15 mm), the
vertical flat walls of which were made out of quartz. It was
fitted with a vertical reflux condenser. The mercury vapor
lamp (Phillips HPK125, 125 W) was placed at 50 mm from
one of the quartz walls, leaning at 45° from the vertical axis.
A 1 mmol amount of the desired thioester and 1 mmol of the
corresponding disulfide, dissolved in 20 mL of dichloromethane,
were introduced in the reaction vessel. Before irradiation, air
was blown off from this solution with nitrogen, under magnetic
stirring. Then, the reaction mixture was illuminated under
stirring, and heat from the lamp brought it to reflux. The
reaction was monitored by GC. At the end of the reaction, the
crude mixture was concentrated under vacuum (without
heating), analyzed by GC, MS, and 19F NMR, and then
separated by chromatography on silica gel (with petroleum
ether or cyclohexane as eluent, unless stated otherwise). Yields
of the resulting compounds are given in Results and Discus-
sion. Their common UV, 19F NMR, and 13C NMR data are given
in Table 7, and their specific analytical data are described
below.
vacuum at room temperature. After recrystallization in pe-
troleum ether, the solid residue affored 1i in a 94% yield (white
1
needles). Mp: 77-78 °C. [R]25 ) +67.8° (c ) 1.2, CHCl3). H
D
NMR: δ 7.24 (m, 1H), 4.92 (m, J AX + J BX + J XNH ) 18.1, 1H),
3.85 (s, 3H), 3.74 (dd, J ) 4.9 and 14.4, 1H), 3.56 (dd, J ) 5.9
and 14.4, 1H). 13C NMR δ 168.00, 157.17 (q, J ) 38.5), 115.44
(q, J ) 289), 63.35, 51.81, 29.99, 13.91. 19F NMR (not reported
in Table 7) δ - 76.40. m/z 327 (M•+), 296, 268, 230, 214, 198,
184, 170, 156, 155, 143, 138, 129, 124, 117, 97, 69. Anal. Calcd
for C8H7F6NO4S: C, 29.37; H, 2.16; N, 4.28; S, 9.80. Found:
C, 29.45; H, 2.12; N, 4.24; S, 9.86.
P r ep a r a tion of n -Octyl P en ta d eca flu or oth ioocta n oa te
(C7F 15C(O)S(CH2)7CH3). A solution of n-octanethiol (0.86 mL,
5 mmol) and DMAP (0.90 g, 7.5 mmol) in anhydrous dichlo-
romethane (12 mL) was cooled at 0 °C. Then, a solution of
pentadecafluorooctanoyl chloride (1.6 mL, 6.5 mmol) in anhy-
drous dichloromethane (10 mL) was dropped on it over 20 min.
After addition, the reaction mixture was kept at room tem-
perature under stirring for 2 h 30 min and then brought to
reflux for 1 h. After cooling, the crude mixture was treated
with trifluoroacetic acid (0.135 mL, 2.5 mmol) and then
separated by flash chromatography on silica gel (10 g) with
dichloromethane as eluent. This chromatography was moni-
tored by GC. The interesting fractions were combined, dried
over MgSO4, and evaporated under vacuum at room temper-
ature to afford 2.29 g of C7F15C(O)S(CH2)7CH3 were obtained
Com m on Sp ectr oscop ic F ea tu r es of CF 3SR (5a -i) a n d
CF 3SeP h (10). See Table 7.
Ad d ition a l Da ta for CF 3SR (1a -i) a n d C7F 15SR (R )
C8H17, CH3).
Octyl Tr iflu or om eth yl Su lfid e (5a ). Oil. 1H NMR: δ 2.87
(t, J ) 7.4, 2H), 1.69 (quint, J ) 7.3, 2H), 1.28 (m, 10H), 0.89
(t, J ) 6.7, 3H). 13C NMR: δ 31.85, 29.50, 29.18, 29.02, 28.62,
22.71, 14.09. MS: m/z 214 (M•+), 195, 145, 129, 115, 83, 69.
Anal. Calcd for C9H17F3S: C, 50.48; H, 7.94; S, 14.95. Found:
C, 50.56; H, 8.12; S, 14.97.
Cycloh exyl Tr iflu or om eth yl Su lfid e (5b). Oil. 1H
NMR: δ 3.25 (m, 1H), 2.06 (m, 2H), 1.75 (m, 2H), 1.7 to 1.2
(m, 1/2 width ) 28 Hz, 6H). 13C NMR: δ. 33.89, 25.74, 25.33.
MS: m/z 184 (M•+), 141, 115, 101, 83, 45.
1
(yield ) 90%). Colorless oil. H NMR: δ 3.1 (t, J ) 7.3, 2H),
1.6 (m, 2H), 1.3 (m, 10H), 0.9 (m, 3H). 13C NMR δ 186.52,
108.96-120.79 (m), 22.63-31.81, 13.78. 19F NMR δ -81.52 (t,
J ) 9.5, 3F), -116.89 (t, J ) 13.2, 2F), -121.81 (broad, 2F),
-122.42 (broad, 4F), -123.20 (broad, 2F), -126.69 (broad, 2F).
P r ep a r a tion of Meth yl P en ta d eca flu or oth ioocta n oa te
(C7F 15C(O)SCH3). A suspension of sodium methanethiolate
(0.14 g, 2 mmol) in anhydrous dichloromethane (5 mL) was
cooled at 0 °C. Then, a solution of pentadecafluorooctanoyl
chloride (0.24 mL, 1.0 mmol) in anhydrous dichloromethane
(5 mL) was dropped on it over 20 min. After addition, the
reaction mixture was kept at room temperature under stirring
for 1 h and then brought to reflux for 2 h. After cooling, the
Eth yl 3-(Tr iflu or om eth ylth io)p r op ion a te (5d ). Oil (elu-
1
ent: petroleum ether/ethyl ether 19:1). H NMR: δ 4.18 (q, J
) 7.3, 2H), 3.13 (t, J ) 7.0, 2H), 2.74 (t, J ) 7.0, 2H), 1.28 (t,
J ) 7.3, 3H). 13C NMR: δ 170.85, 61.02, 34.78, 24.74, 14.08.
MS: m/z 202 (M•+), 157, 133, 129, 115, 105, 87, 69, 45.
Ben zyl Tr iflu or om eth yl Su lfid e (5e). Oil. 1H NMR: δ
7.34 to 7.25 (m, 5H), 4.09 (s, 2H). 13C NMR: δ 135.04, 128.95,
128.89, 128.04. MS: m/z 192 (M•+), 91, 65.
P h en yl Tr iflu or om eth yl Su lfid e (5f). Oil. Bp760: 140 °C.
1H NMR: δ 7.66 (dd, J ) 7.9 and 1.6, 2H), 7.47 to 7.34 (m,
3H). 13C NMR: δ 136.54 (q, J ) 0.9), 130.82, 129.48. MS: m/z
178 (M•+), 159, 109, 108, 77, 69.

3820 J . Org. Chem., Vol. 64, No. 11, 1999
Billard et al.
4-Ch lor op h en yl Tr iflu or om eth yl Su lfid e (5g). Oil. 1H
NMR: δ 7.59 (d, J ) 8.5, 2H), 7.39 (d, J ) 8.5, 2H). 13C NMR:
δ 137.76, 137.63 (q, J ) 1.0), 129.85. MS: m/z 214 (M•+), 212,
193, 145, 143, 108, 99, 69, 45.
Eth yl 2-(Tr iflu or om eth ylth io)a ceta te (5h ). Oil (eluent:
petroleum ether/diethyl ether 95:5, then 80:20). 1H NMR: δ
4.24 (q, J ) 7.1, 2H), 3.66 (s, 2H), 1.27 (t, J ) 7.1, 3H). 13C
NMR: δ 167.65, 62.36, 14.00. MS: m/z 188 (M•+), 143, 115,
75, 69, 46, 45, 42, 29.
Meth yl N-(Tr iflu or oa cetyl)-S-(tr iflu or om eth yl)-(L)-cys-
tein a te (5i). Mp: 53 °C. [R]D25 ) +58.5 ° (C ) 0.8, CHCl3).
1H NMR: δ 7.36 (m, 1H), 4.91 (m, ΣJ ) 16.8, 1H), 3.85 (s,
3H), 3.57 (dd, J ) 14.9 and 4.6, 1H), 3.37 (dd, J ) 14.9 and
Cr oss-Cou p lin g Tr iflu or om et h yla t ion s. Tr iflu or o-
m eth yla tion of Dieth yl 3,3′-Dith iod ip r op ion a te (4d ) w ith
ter t-Bu tyl Tr iflu or oth ioa ceta te (1c). Following the general
photolysis procedure, a mixture of 1c (0.21 g, 1.1 mmol), 4d
(0.26 g, 0.98 mmol), and dichloromethane (20 mL) was irradi-
ated at 40 °C for 1.5 h. After illumination, (trifluoromethoxy)-
benzene (0.037 g, 0.23 mmol), used as internal standard for
19F NMR analysis, was added to the cooled reaction mixture,
in which the corresponding spectrum revealed the presence
of 1c (0.100 mmol), 5c (0.143 mmol), 5d (0.335 mmol), 8c
(0.013 mmol), 8d (0.026 mmol), and a vinylic trifluorometh-
ylated product (0.067 mmol). The crude mixture was evapo-
rated at room temperature under vacuum to deliver an orange
oil (0.400 g) which was submitted to flash chromatography over
silica gel (14 g) with, first, 200 mL of petroleum ether/diethyl
ether (95:5) and then 200 mL of petroleum ether/diethyl ether
(80:20). The pale yellow oil, resulting from the first elution,
contained 5d (0.20 mmol), 8d (0.02 mol), and ethyl 3-(tert-
butyldithio)propionate (0.45 mmol), as indicated from 19F and
1H NMR with PhOCF3 as internal standard. The second
fraction was quite almost constituted of 4d .
5.1, 1H). 13C NMR: δ 168.62, 157.26, 109.85, 53.64, 52.40. 19
F
NMR: δ -76.41 (CF3CONH). MS: m/z 299 (M•+), 280, 268,
240, 202, 198, 186, 184, 170, 138, 124, 117, 115, 97, 69, 59,
45.
Octyl P en ta d eca flu or oh ep tyl Su lfid e. Oil. 19F NMR: δ
-126.37 (broad, 2F), -122.96 (broad, 2F), -122.22 (broad, 2F),
-121.46 (broad, 2F), -120.08 (broad, 2F), -87.68 (t, J ) 12,
2F), -81.09 (t, J ) 9, 3F).
Meth yl P en ta d eca flu or oh ep tyl Su lfid e. Oil. 1H NMR:
δ 2.4 (s). 19F NMR: δ -126.87 (broad, 2F), -123.46 (broad,
2F), -122.73 (broad, 2F), -122.05 (broad, 2F), -120.35 (broad,
2F), -90.92 (t, J ) 14, 2F), -81.29 (t, J ) 8.5, 3F).
Ad d ition a l Da ta for CF 3SeP h (10). P h en yl Tr iflu or o-
m eth yl Selen id e (10). Oil. 13C NMR: δ 137.09 (q, J ) 0.7),
130.33, 129.59. MS: m/z 226 (M•+), 157, 127, 77, 69, 65, 50.
Anal. Calcd for C7H5F3Se: C, 37.36; H, 2.24; Se, 35.08.
Found: C, 36.99; H, 2.21; Se, 35.13.
Eth yl 3-(ter t-Bu tylth io)p r op ion a te. 1H NMR: δ 4.14 (q,
J ) 7.5, 2H), 2.92 (t (broad), 2H), 2.69 (t (broad), 2H), 1.33 (s,
9H), 1.25 (t, J ) 7.5, 3H). 13C NMR: δ 171.84, 60.73, 47.95,
35.13, 34.45, 29.99, 14.23. MS: m/z 222 (M•+), 177, 166, 165,
121, 120, 101, 87, 73, 57, 45.
Tr iflu or om eth yla tion of Dieth yl 3,3′-Dith iod ip r op i-
on a te (4d ) w ith Octyl Tr iflu or om eth a n eth iosu lfon a te
(2a ). As above, a mixture of 2a (0.278 g, 1 mmol), 4d (0.266 g,
1 mmol), and dichloromethane (20 mL) was irradiated at 40
°C for 40 min. Analysis of the resulting crude mixture by GC
coupled with MS indicated the presence of 4a , 4d , and ethyl
3-(octyldithio)propionate in similar amounts.
Sp ectr oscop ic Da ta for Byp r od u cts F or m ed d u r in g
P h ot olysis E xp er im en t s. Ch lor om et h yl Oct yl Su lfid e
(6a ). MS: m/z 196 (M•+ + 2), 194 (M•+), 159, 145, 97, 95, 83,
49, 45.
Eth yl 3-(Octyld ith io)p r op ion a te. MS: m/z 278 (M•+), 233,
132, 120, 101, 29.
Ch lor om eth yl c-Hexyl Su lfid e (6b). MS: m/z 166 (M•+
+ 2), 164 (M•+), 129, 115, 83, 82, 45.
Tr iflu or om eth yla tion of Dim eth yl N,N′-Bis(tr iflu or o-
a cetyl)-(L)-cystin a te (4i) w ith Eth yl Tr iflu or oth ioa ceta te.
A mixture of anhydrous acetonitrile (20 mL), ethyl trifluo-
rothioacetate (0.086 g, 0.55 mmol) and 4i (0.23 g, 0.50 mmol)
was introduced in the reaction vessel, purged for 10 min with
dry nitrogen at room temperature, and then illuminated under
stirring at 40 °C for 45 min. After addition of more ethyl
trifluoroacetate (0.086 g), illumination at 40 °C was continued
for 1 h. This latter procedure was repeated twice. Reaction
progress was monitored by GC. After irradiation (3 h 45 min),
cooling, and addition of PhOCF3 (0.037 g, 0.23 mmol) as
internal standard, ethyl trifluoromethyl sulfide (δ -41.13 (s),
1.01 mmol) and 5i (0.29 mmol) were detected by 19F NMR in
the crude reaction mixture, as well as some other trifluoro-
acetylated compounds. This crude mixture was concentrated
at room temperature under vacuum. Then, the resulting brown
oil (0.32 g) was purified by flash chromatography on silica gel
with, first, petroleum ether/ethyl acetate (95:5), second, pe-
troleum ether/ethyl acetate (80:20), and, finally, ethyl acetate.
Though 5i was the major component of the first fraction and
methyl S-(ethylthio)-N-trifluoroacetyl-(L)-cysteinate the major
component of the second fraction, these two compounds could
not be clearly separated. The combined two fractions contained
5i (65 mg, 0.22 mmol) and methyl S-(ethylthio)-N-(trifluoro-
acetyl)-(L)-cysteinate (85 mg, 0.30 mmol). The third fraction
contained unreacted 4i.
Eth yl 3-(Ch lor om eth ylth io)p r op ion a te (6d ). MS: m/z
184 (M•+ + 2), 182 (M•+), 147, 139, 137, 133, 111, 109, 102,
101, 97, 95, 87, 74, 73, 59, 45.
Dich lor om eth yl Octyl Su lfid e (7a ). MS: m/z 230 (M•+
+
2), 228 (M•+), 195, 193, 145, 87, 85, 83, 45.
Dich lor om eth yl c-Hexyl Su lfid e (7b). MS: m/z 200 (M•+
+ 2), 198 (M•+), 165, 163, 115, 83, 82, 45.
Eth yl 3-(Dich lor om eth ylth io)p r op ion a te (7d ). MS: m/z
220 (M•+ + 4), 218 (M•+ +2), 216 (M•+), 183, 181, 175, 173,
171, 147, 145, 143, 117, 95, 93, 87, 73, 59, 45.
Octyl Tr iflu or om eth yl Disu lfid e (8a ). 19F NMR:
-46.68 (s). MS: m/z 246 (M•+), 145, 133, 101, 71, 69, 45.
c-Hexyl Tr iflu or om eth yl Disu lfid e (8b). 19F NMR:
δ
δ
-46.61 (s). 13C NMR: δ 129.40 (q, J ) 314), 50.19, 32.37, 25.89,
25.49. MS: m/z 216 (M•+), 133, 115, 83, 69, 45.
ter t-Bu tyl Tr iflu or om eth yl Disu lfid e (8c). 19F NMR: δ
-45.57 (s).
Eth yl 3-(Tr iflu or om eth yld ith io)p r op ion a te (8d ). 19F
NMR: δ -46.61 (s). MS: m/z 234 (M•+), 189, 161, 147, 133,
105, 87, 73, 69, 59.
Ben zyl Tr iflu or om eth yl Disu lfid e (8e). 19F NMR:
δ
-47.01.
P h en yl Tr iflu or om eth yl Disu lfid e (8f). 19F NMR:
-46.40 (s,). MS: m/z 210 (M•+), 141, 109, 77, 69, 65.
δ
4-Ch lor op h en yl Tr iflu or om eth yl Disu lfid e (8g). 19F
NMR: δ -46.27 (s). MS: m/z 246 (M•+), 244 (M•+), 175, 143,
108, 69.
Met h yl S-(E t h ylt h io)-N-(t r iflu or oa cet yl)-(L)-cyst ein -
a te. 1H NMR: δ 7.41 (m, broad, 1H), 4.92 (m, 1/2 width )
20.7, 1H), 3.32 (s, 3H), 3.32 to 3.12 (m, ∆ν/J < 2, 2H), 2.73 (q,
J ) 7.3, 2H), 1.32 (t, J ) 7.3, 3H). 13C NMR: δ 169.41, 156.90
(q, J ) 38), 115.59 (q, J ) 288), 53.20, 52.27, 39.27, 32.72,
14.21. 19F NMR: δ -76.41. MS: m/z 291 (M•+), 232, 198, 184,
178, 170, 138, 117, 107, 93, 79, 69, 61, 59, 45, 43, 29.
Eth yl 2-(Tr iflu or om eth yld ith io)a ceta te (8h ). 19F
NMR: δ -46.56 (s).
P h en yl (Tr iflu or om eth yl)p h en yl Disu lfid e (9f; th r ee
isom er s). 19F NMR: δ -60.50 (s) and -63.00 (s). MS: first
isomer m/z 286 (M•+), 267, 222, 177, 157, 109, 77, 69; second
isomer m/z 286 (M•+), 267, 222, 177, 157, 109, 77, 69; third
isomer m/z 286 (M•+), 218, 185, 154, 141, 109, 77, 69.
J O980649A