Acid Catalyzed α-Trifluoromethylthiolation
source (NH4Cl) was added to preclude this OH–ClSiMe3
interaction. In this way, a good yield of trifluoromethyl-
thiolation was obtained (3v).
Experimental Section
Ketone (0.50 mmol, 1.0 equiv.) in dry MeCN (1 mL) followed by
TsNMeSCF3 (1a; 0.60 mmol, 1.2 equiv.) were added to a 10 mL
sealed tube equipped with a magnetic stirrer. The reaction mixture
was stirred at room temperature for 1 min, TMSCl was added and
the reaction was stirred at 90 °C for 18 h. The conversion was
checked by 19F NMR with PhOCF3 as internal standard. After
completion, the reaction mixture was cooled to room temperature,
the solvent was removed under vacuum and the residue was puri-
fied by flash column chromatography to afford the expected prod-
uct.
The same reaction was also extended to aldehydes that
were difficult to trifluoromethylthiolate under basic condi-
tions (Figure 2).[16a] However, depending on the aldehyde,
the reaction conditions should be adapted to achieve good
yields. Indeed, the aldehydes are very reactive in acid-cata-
lyzed conditions and the auto-aldol reaction competes with
the reaction with activated 1. Consequently, optimal com-
promises had to be found to favor the expected reaction
against the side reaction.
Acknowledgments
We thank A. Baudoin and B. Fenet (University NMR Centre) for
their help in the determination of diastereomer configurations. The
Centre National de la Recherche Scientifique (CNRS) and the
French Ministry of Research are thanked for their financial sup-
port. The French Fluorine Network is also thanked for its support.
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Conclusions
To conclude, we have described a new soft-acid-catalyzed
method, complementary to the basic conditions previously
described, to obtain selectively mono-α-trifluoromethyl-
thiolated carbonyl compounds. This strategy allows the syn-
thesis of valuable trifluoromethylthiolated molecules for
various further applications. This method is also compatible
with more elaborate compounds for a late trifluoromethyl-
thiolation. This work demonstrates that the second genera-
tion of trifluoromethanesulfenamide (1) is a valuable rea-
gent to obtain various α-trifluoromethylthiolated carbonyl
compounds under various conditions, depending on the
starting substrate.
Eur. J. Org. Chem. 2015, 4607–4610
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