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G. Blond et al. / Tetrahedron Letters 42 (2001) 2473–2475
Table 2. Reactivity of 2 or 3 toward disulfides and diselenides
Entry
RYYR
2 or 3 (x equiv.)
F−
q (°C)
4 or 5 (%)a
1
2
3
4
5
6
7
8
PhSSPh
PhSSPh
(c-C6H11S)2
PhSSPh
PhSSPh
2 (2)
2 (2)
2 (2)
3 (1)
3 (2)
3 (2)
3 (1)
3 (2)
3 (2)
3 (2)
3 (2)
3 (2)
3 (2)
CsF
80
80
80
60
60
80
60
60
80
80
80
80
80
(50) 4a
TBATb
TBAT
TBAT
TBAT
TBAT
TBAT
TBAT
TBAT
TBAT
TBAT
TBAT
TBAT
70 (90) 4a
82 (90) 4c
(43) 4a
69 (78) 4a
(95) 4a
PhSSPh
(c-C6H11S)2
(c-C6H11S)2
(n-C8H17S)2
(tert-BuS)2
(p-Cl-PhS)2
PhSeSePh
(p-Cl-PhSe)2
(54) 4c
70 (75) 4c
87 (97) 4b
(5) 4d
86 (95) 4e
80 (92) 5a
80 (75) 5b
9
10
11
12
13
a Isolated yield. In parentheses: crude yield determined by 19F NMR with internal standard (PhOCF3).
b TBAT: tetrabutylammonium triphenyldifluorosilicate (De Shong’s reagent).
Although the result was satisfactory with diphenyl
disulfide (entry 1), it was very disappointing with
dioctyl disulfide (entry 3). This low yield could be
explained by an a-deprotonation of the disulfide by the
basic system, which strongly competed with trifluo-
romethylation. When di(4-chorophenyl)disulfide was
used as substrate, only 35% of an undetermined
product was obtained (entry 2). This compound was
too unstable to be isolated and characterized.
Finally, the optimal results were obtained with 2 equiv.
of 2 or 3 and 2 equiv. of TBAT, the reaction being
carried out at 80°C for 5 h.12
This reaction allows the preparation of trifluoromethyl
sulfides in high yields either in the aromatic or the
aliphatic series (Table 2). The low yield obtained from
di(tert-butyl) disulfide can be rationalized by a high
steric hindrance around the sulfur atom.
Because of these limited results, we focused our interest
on silylated reagents 2 and 3 (Table 2).
Trifluoromethyl selenides, which are quite unknown
compounds, can be also synthesized very easily by this
way (entries 12 and 13).
By analogy with our previous studies on the reaction of
CF3SiMe3 with disulfides, we used a stoichiometric
amount of fluoride ions (versus RSSR).6 The low solu-
bility of CsF in 1,2-dimethoxyethane (glyme) allowed
us to obtain medium yields only (entry 1) whereas the
soluble, and commercially available, De Shong’s
fluoride11 (TBAT: (Ph3SiF2)−Bu4N+) provided a good
result (entry 2).
In conclusion, we have demonstrated that hemiaminals
of fluoral, which constitute a new family of trifluo-
romethylating agents, can be also used for the synthesis
of trifluoromethylchalcogenides from dichalcogenides.
Others investigations on the scope and limitations of
these new reagents are currently under study in our
laboratory.
As with CF3SiMe3,6 the morpholino derivative 2 gave
good results when 2 equiv. were used (entries 2 and 3).
References
We have previously shown that the N-benzylpiperazino
derivative 3 is more efficient than 2.9 Thus, 3 was also
opposed to disulfides. Table 2 indicates that medium
yields were obtained with 1 equiv. of 3 whereas good
yields were reached with 2 equiv. (entries 4–5 and 7–8).
Also, the same temperature was required to get similar
yields from 2 and 3 (entries 5 and 6). Thus, in contrast
with the reaction on ketones, 2 and 3 exhibited the
same reactivity towards disulfides. This fact could be
explained by the low electrophilicity of disulfides com-
pared to that of carbonyl compounds.
1. Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91,
165–195.
2. (a) Langlois, B. R.; Billard, T.; Large, S.; Roques, N.
Fluorinated Bio-active Compounds; Fluorine Technology
Ltd: Cheshire, 1999; Paper 24; (b) Hiyama, T.
Organofluorine Compounds Chemistry and Applications;
Springer: Berlin, 2000; Chapter 5; (c) Banks, R. E.;
Smart, B. E.; Tatlow, J. C. Organofluorine Chemistry:
Principles and Commercial Applications; Plenum Press:
New York, 1994.