Fluorodesilylation of alkenyltrimethylsilanes: A new route to fluoroalkenes and difluoromethyl-substituted amides, alcohols or ethers

Article abstract of DOI:10.1039/b009179k

A range of alkenyltrimethylsilanes are converted to alkenyl fluorides by reaction with one equivalent of Selectfluor (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)), or difluoromethyl-substituted alcohols, ethers or amides using an excess of Selectfluor in the presence of various nucleophiles.

Full text of DOI:10.1039/b009179k

Fluorodesilylation of alkenyltrimethylsilanes: a new route to fluoroalkenes and
difluoromethyl-substituted amides, alcohols or ethers
Benjamin Greedy and Veronique Gouverneur*
University of Oxford, The Dyson Perrins Laboratory, South Parks Road, Oxford, UK OX1 3QY.
E-mail: veronique.gouverneur@chem.ox.ac.uk; Phone and Fax: +44 1865 275 644
Received (in Liverpool, UK) 9th November 2000, Accepted 19th December 2000
First published as an Advance Article on the web 16th January 2001
A range of alkenyltrimethylsilanes are converted to alkenyl
fluorides by reaction with one equivalent of Selectfluor™
(1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane
bis(tetrafluoroborate)), or difluoromethyl-substituted alco-
hols, ethers or amides using an excess of Selectfluor™ in the
presence of various nucleophiles.
1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis-
(trifluoromethanesulfonate) was allowed to react with an
equimolar amount of compound 1a in acetonitrile, fluoro-
desilylation occurred to afford the fluoroalkene 2a with a
conversion of 32%. In contrast, 1-fluoropyridinium pyridine
heptafluorodiborate and N-fluorobenzenesulfonimide did not
react with compound 1a. These results prompted us to use
Selectfluor™ for subsequent fluorodesilylation reactions. A
series of alkenyltrimethylsilanes 1b–f was thus prepared
according to known literature procedures7,9 in order to evaluate
the scope and limitation of this reaction. The expected
fluoroalkenes 2b,c were obtained as Z+E mixtures in moderate
to good yields (Table 1, entries 2 and 3 ). In terms of
mechanism, the reaction of 1a to form 2a might involve an
In view of the unique features of fluorine-containing com-
pounds, there has been an increasing interest in the development
of novel methods for the synthesis of fluorinated molecules.1 In
particular, terminal fluoroalkenes have been used in the design
of a number of mechanism-based enzyme inhibitors and other
bioactive molecules.2 Consequently, development of general
methodologies for their preparation is an important challenge.
Our studies were initiated in order to investigate the hypothesis
that electrophilic N–F reagents3 would react with alkenyl-
trimethylsilanes to give the corresponding alkenyl fluorides.
Fluorodesilylations of aryltrimethylsilanes using xenon di-
fluoride and elemental fluorine have been reported respectively
by Lothian and Ramsden4 and by Stuart et al.5 Surprisingly, in
contrast to chloro-, bromo- or iododesilylation,6 fluorodesilyla-
tion has never been applied to alkenylsilanes. In addition, the
reactivity of the N–F group of reagents has not been
investigated for a fluorodesilylation processes. In this commu-
nication, we demonstrate a new and facile approach for the
synthesis of alkenyl fluorides as well as difluoromethyl-
substituted alcohols, amides and ethers.
Table 1 Fluorodesilylation of vinylsilane derivatives 1a–f
The substrate trimethylstyrylsilane 1a was prepared as a
mixture of stereoisomers (E+Z/8+92).7 The fluorodesilylation
was attempted with several commercially available N–F
reagents. The reaction of compound 1a with 1 eq. of
Selectfluor™ in acetonitrile at rt afforded the expected fluoro-
alkene 2a with a conversion8 of 47% after 20 h (Scheme 1, eqn
1 and Table 1, entry 1). Prolonged reaction times did not
improve the yield of compound 2a as the formation of a second
product was observed instead. This product was identified as
difluoroamide 3a and is believed to result from further
fluorination of 2a followed by reaction with acetonitrile. When
Scheme 1
DOI: 10.1039/b009179k
Chem. Commun., 2001, 233–234
This journal is © The Royal Society of Chemistry 2001
233

addition–elimination pathway via a carbocationic intermediate.
The formation of a mixture of geometrical isomers and the
faster reaction with more nucleophilic vinylsilanes are con-
sistent with this mechanism.
Notes and references
† Procedure for the production of 6f: A solution of 5-phenyl-6-trimethyl-
silanyl hex-5-en-1-ol (350 mg, 1.4 mmol) in acetonitrile (35 ml) was treated
with Selectfluor™ (1.24 g, 3.5 mmol) and stirred at rt for 48 h. The reaction
mixture was poured into saturated aqueous sodium hydrogen carbonate (30
ml) and extracted with diethyl ether (3 3 30 ml). The combined organic
phases were dried (MgSO4) and concentrated in vacuo. Purification of the
residue by silica gel chromatography (1+1 hexane–DCM, Rf = 0.48) gave
the product as a colourless oil (142 mg, 48%); 1H NMR (400 MHz, CDCl3):
1.42–1.52 (m, 2H), 1.69–1.79 (m, 2H), 1.96 (td, 1H, J = 13.6, J = 4Hz),
3.53 (td, 1H, J = 12.4Hz, 2.4), 3.80–3.84 (m, 1H), 5.57 (t, 1H, J = 57.2
Hz), 7.35–7.50 (m, 5H); 13C NMR (100.6 MHz, CDCl3): 18.4, 25.3(t, J =
2.3Hz), 25.6, 29.7, 62.5, 117.1 (t, J = 247.8 Hz), 128.1, 128.3, 128.6 and
Treatment of alkenylsilanes 1a–d with more than one
equivalent of Selectfluor™ produced the corresponding vicinal
difluoroamides 3a, 3c and 3d in good yields by a Ritter-type
fluoro-functionalisation with acetonitrile (Scheme 1, eqn. 2 and
Table 1, entries 4, 6 and 7). The reaction could not be applied to
1b since the corresponding primary product of the reaction, the
fluoroalkene 2b, failed to react any further (Table 1, entry 5).
These results are consistent with the observation made earlier
by Stavber et al.10 who reported that monofluoroamides could
be prepared from the corresponding alkene by a “fluoro-Ritter”
reaction. More recently, Olah et al.11 also reported the
formation of difluoroamides by electrophilic fluorination of
alkenyl boronic acids and trifluoroborates.
135.4; 19F NMR (235.3 MHz, CDCl3): 2131.1, 2131.9 (dxAB, JF–F
=
277.6 Hz, JH–F = 56.5 Hz); HRMS calcd. for C12H18NOF (M + NH4)+
230.1356, found 230.1349.
When the reaction was carried out in aqueous acetonitrile or
in a mixture of methanol and acetonitrile, the product outcome
was different (Scheme 1, eqn. 3). When the alkenyltrimethyl-
silanes 1a and 1c were treated with 2.5 eq. of Selectfluor™ in a
1+1 mixture of MeOH–CH3CN, the corresponding difluoro-
methyl ether derivatives 4a and 4c were prepared in 75 and 79%
yield respectively (Table 1, entries 8 and 10). Similarly, when
compounds 1a and 1c were treated with 2.5 eq. of Selectfluor™
in a 1+1 mixture of H2O+CH3CN, the difluoromethyl alcohols
5a and 5c were obtained with chemical yields of 45 and 83%
(Table 1, entries 9 and 11). The difluoroamides were always
formed as side products but could be easily separated by silica
gel chromatography. In addition, the methodology can also be
applied to the preparation of the bis-fluorinated tetrahydrofuran
6e and the tetrahydropyran 6f† by treating the corresponding
alkenyltrimethylsilanes 1e and 1f with 2.5 eq. of SelectfluorTM
in acetonitrile (Table 1, entry 12).
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medical Applications, ed. R. Filler, Y. Kobayashi and L. M. Yagu-
polskii, Elsevier, Amsterdam, 1993; (b) Fluorine-Containing Amino
Acids: Synthesis and Properties, ed. V. P. Kukhar and V. A.
Soloshonok, John Wiley & Sons, Chichester, 1995.
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179.
In summary, substituted alkenylsilanes carrying electron-
donating groups undergo smooth mono- or bis-electrophilic
fluorination to afford fluoroalkenes or vicinal difluoroamides,
alcohols or ethers. The present report opens new possibilities for
the direct and effective preparation of alicyclic and cyclic
difluorinated derivatives. Mechanistic investigations along with
the evaluation of the scope and limitation of this novel
methodology are in progress in our laboratory. The generous
financial support of Rhodia Organique Fine is acknowledged.
We also thank Dr J. M. Paris, Dr J. R. Desmurs, and Dr J.
Russell for very helpful suggestions regarding this work.
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8 The term ‘conversion’ is used here to mean the total % of product
detected in the reaction mixture by GCMS before isolation.
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Chem. Commun., 2001, 233–234