Ro¨schenthaler has carried out perfluoroalkylation of various
substrates using (perfluoroalkyl)trimethylsilanes and perflu-
orinated phosphonate reagents by following different syn-
thetic strategies.8 Recently, Dolbier and co-workers9 reported
the use of C2F5I with tetrakis(dimethylamino)ethylene (TDAE)
in the nucleophilic perfluoroalkylation reactions of aldehydes,
ketones, imines, disulfides, and diselenides. In addition, the
C2F5I/CH3Li system originally developed by Gassman et al.10
and ultrasound-promoted C2F5X (X ) Br, I)/Zn system by
Kitazume et al.11 were also documented for the introduction
of pentafluoroethyl group to carbonyl compounds. However,
alkoxide-induced nucleophilic pentafluoroethylation using
pentafluoroethyl sulfone 1 has not been investigated.
Scheme 2. Perfluoroalkylation of Imines Using PhSO2RF
Nucleophilic addition reactions between PhSO2CF2CF3 (1)
and imines (3) were performed under argon atmosphere by
slowly adding a base into the mixture of 1 and 3 in DMF
(Scheme 2). Optimization of reaction conditions for base
(alkoxide) induced perfluoroalkyl transfer to imines was
smooth, and the results are shown in Table 1.
Our previous studies12 showed that trifluoromethyl phenyl
-
sulfone 2 can be used as a “CF3 ” synthon in the presence
of potassium tert-butoxide (t-BuOK) for efficient trifluo-
romethylation of nonenolizable carbonyl compounds and
disulfides. However, the trifluoromethylation and pentafluo-
roethylation of imines by the corresponding perfluoroalkyl
sulfones have not been investigated. Herein, we wish to
report the successful alkoxide-induced nucleophilic pen-
tafluoroethylation and trifluoromethylation of aldehydes,
ketones, and imines by using pentafluoroethyl phenyl sulfone
(1) and trifluoromethyl phenyl sulfone (2), respectively. The
chemistry behind this simple and highly feasible transforma-
tion is based on the nucleophilic attack of the alkoxide ion
on the thio center of 1 or 2 resulting in the generation of
Table 1. Optimization of Reaction Conditions for the
-
Introduction of CF3CF2 into Imines
sulfone imine
-
1
3
t-BuOK
temp time yield
(°C) (h) (%)
pentafluoroethyl anion (“CF3CF2 ”) or trifluoromethyl anion
-
entry (equiv) (equiv) (equiv) solvent
(“CF3 ”) in situ (Scheme 1).
1
2
3
4
1.0
1.5
1.5
1.5
2.0
1.0
1.0
1.0
2.0
6.0
6.0
4.5
DMF -30 to rt 1.5 34a
DMF -65
DMF -55
THF -78
1.5 69b
1.5 mixturec
1.5 99b
Scheme 1
.
Alkoxide Induced “RF-” Generation from
Perfluorosulfones
a Yield was estimated by 19F NMR. b Isolated yields. c Yield was not
determined.
In order to find the most effective reaction conditions and
enhance the yields, the reaction has been conducted by
changing reaction parameters such as solvents, reaction
temperatures, and reactant ratios. A previous study12 dem-
onstrated that DMF as a solvent and t-BuOK as a base were
the apt choice for trifluoromethylation reaction using
PhSO2CF3 (2). Therefore, we initially applied the similar
reaction conditions for the pentafluoroethylation reaction
using PhSO2CF2CF3 (1). However, the yield was low and
the reaction was not complete. By modifying the reaction
conditions as before,12a,b we found that low temperatures
and slight excess of sulfone 1 and large excess of t-BuOK
favored the reaction. When the temperature was lowered to
-78 °C with THF as solvent instead of DMF, the yield was
found to be almost quantitative (99%, Table 1, entry 4). After
carefully modifying the reaction conditions, we ascertained
that good yield (60-99%) can be obtained by the dropwise
addition of 4.5 equiv of t-BuOK in THF to the mixture of
1.5 equiv of the perfluoroalkyl sulfone 1 and 1 equiv of imine
3 in THF at -75 to -70 °C followed by stirring the mixture
for 1.5 h under argon atmosphere. The results are sum-
marized in Table 2.
The fluorine reagent, trifluoromethyl phenyl sulfone (2),
is commercially available. Pentafluoroethyl phenyl sulfone
was prepared in good yields from the reaction13 between
potassium pentafluoropropionate (CF3CF2COOK) and di-
phenyl disulfide followed by oxidation.
(8) (a) Cherneka, A. N.; Kolomeitsev, A. A.; Yagupolskij, Y. L.;
Gentzsch, A.; Ro¨shenthaler, G.-V. J. Fluorine Chem. 1994, 70, 271. (b)
Sosnovskikh, V. Ya.; Sevenard, D. V.; Usachev, B. I.; Ro¨shenthaler, G.-V.
Tetrahedron Lett. 2003, 2097. (c) Sonovskikh, V. Y.; Usachev, B. I.;
Sevenard, D. V.; Ro¨shenthaler, G.-V. J. Org. Chem. 2003, 68, 7747. (d)
Tverdomed, S. N.; Ro¨shenthaler, G.-V.; Kalinovich, E. L.; Dogadina, A. V.;
Ionin, B. I. J. Fluorine Chem. 2008, 129, 478.
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(12) (a) Prakash, G. K. S.; Hu, J.; Olah, G. A. Org. Lett. 2003, 5, 3253.
(b) Prakash, G. K. S.; Hu, J.; Mathew, T.; Olah, G. A. Angew. Chem., Int.
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Org. Lett., Vol. 12, No. 13, 2010
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