LETTER
Synthesis of b-Trifluoromethylated Enones
1243
(5) Leuger, J.; Blond, G.; Fröhlich, R.; Billard, T.; Haufe, G.;
Langlois, B. R. J. Org. Chem. 2006, 71, 2735.
O
OH
CF3
O
1) MsCl (1.2 equiv)
Et3N (1 equiv), CH2Cl2
CF3
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2) Et3N (1.5 equiv)
6f
7 73%
Scheme 7 Dehydration of 6f
This isomerization is due to the use of basic conditions
which allow the deprotonation of allylic proton driving to
the conjugation of the double bond. This isomerization
occurs during the mesylation step since the formation of 7
is already observed before the second addition of Et3N.
This means that such an isomerization is base-catalyzed.
Compound 7 constitutes an interesting building block for
the design of new trifluoromethylated molecules, espe-
cially (hetero)cyclic ones.
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To conclude, two new routes to b-trifluoromethylated
enones, starting from ethyl trifluoroacetoacetate, have
been described. These methodologies open an access to
alkyl enones which are difficult to obtain with the previ-
ously described methods. An unexpected conjugated ad-
dition of organolithium has been observed onto b-
trifluoromethylated-a,b-unsaturated Weinreb amide has
been observed. Such surprising regioselectivities are to
this day difficult to rationalize and ab initio calculations
should be realized.
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Acknowledgment
We thank the CNRS and the Bayer Cropscience Co. for financial
support.
References and Notes
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622.
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(15) Typical Experimental Procedure – Synthesis of 1
To a nitrogen-flushed suspension of N,O-dimethylhydroxyl-
amine hydrochloride (11.70 g, 120 mmol) in 50 mL of anhyd
CH2Cl2 was added AlMe3 (2 M in heptane, 60 mL, 120
mmol) drop by drop at –10 °C. The resulting yellow solution
was stirred at r.t. for 1 h, cooled to –10 °C and a soln of 4
(10.7 g, 58.1 mmol) in 10 mL of anhyd CH2Cl2 was slowly
added. The reaction mixture was stirred at r.t. overnight, then
carefully quenched at –10 °C with a sat. aq soln of NH4Cl.
After extraction of the mixture with Et2O, the organic layers
were combined, washed with H2O, dried over anhyd MgSO4,
filtered, and concentrated in vacuo to give 1 (10.64 g, 91%)
as white crystals; mp 63–64 °C. 1H NMR: d = 4.91 (br s, 1
H), 4.48 (ddq, J = 9.5, 2.6, 6.9 Hz, 1 H), 3.71 (s, 3 H), 3.20
(s, 3 H) 2.87 (dd, J = 16.8, 9.5 Hz, 1 H), 2.70 (dd, J = 16.8,
2.6 Hz, 1 H). 13C NMR: d = 171.3, 125.3 (q, J = 281.0 Hz),
67.2 (q, J = 31.8 Hz), 61.7, 32.4 (q, J = 1.8 Hz), 32.3.
19F NMR: d = –80.02 (d, J = 6.9 Hz). Anal. Calcd for
C6H10F3NO3: C, 35.83, H, 5.01. Found: C, 35.98, H, 4.97.
Synthesis of Ketols 6
To a solution of 1 (1 equiv) in anhyd THF (2 mL, 1 mmol)
was slowly added at –78 °C the organometallic reagent (2
equiv) under inert atmosphere. The reaction mixture was
stirred at this temperature for 4 h, then warmed to 0 °C and
quenched with a sat. aq soln of NH4Cl. After extraction of
the mixture with Et2O, the organic layers were combined,
washed with brine, dried over anhyd MgSO4, filtered, and
concentrated in vacuo to give 6.
Synlett 2009, No. 8, 1241–1244 © Thieme Stuttgart · New York