Trifluoromethylated Vinylic and Aromatic Compounds from α-(Trifluoromethyl)allyl Alcohols

Article abstract of DOI:10.1055/s-2004-815928

α-(Trifluoromethyl)allyl alcohols, easily available from α,β-unsaturated carbonyl compounds, are readily converted into γ-(trifluoromethyl)allyl thioethers, benzyl ethers, trifluoroacetates, and azides. A phenyl substituent at the γ-position to the hydroxyl function enhances their reactivity and the ease of S_N2′ or S_N1′ substitutions, whereas a phenyl ring at the α-position allows the BF₃-mediated synthesis of (trifluoromethyl)indenes. 4-Alkyl-4-methoxy-1-(trifluoromethyl)cyclohexa-2,5- dienols, readily available from 4-alkylphenols, are easily converted to 4-alkyl(trifluoromethyl)benzenes bearing a nucleophilic substituent (MeO, Cl) either on the ring or the benzylic position.

Full text of DOI:10.1055/s-2004-815928

456
FEATURE ARTICLE
Trifluoromethylated Vinylic and Aromatic Compounds from -(Trifluoro-
methyl)allyl Alcohols
T
rifluorometh
y
l
c
a
nd A
v
romatic Com
i
pound
e
s
from
-
(Trifluo
R
romethyl)allyl
A
a
lcohols dix-Large, Stéphanie Kucharski, Bernard R. Langlois*
Université Claude Bernard-Lyon I, Laboratoire SERCOF (UMR 5181), 43 Bd du 11 Novembre 1918, 69622 Villeurbanne Cedex (France)
Fax +33(4)72431323; E-mail: Bernard.Langlois@univ-lyon1.fr
Received 14 November 2003
(trifluoromethyl)-2-buten-1-ol dramatically decreases the
Abstract: -(Trifluoromethyl)allyl alcohols, easily available from
transfer of isopentenyl pyrophosphate by farnesyl pyro-
phosphate synthase and farnesyl transferase and thus be-
, -unsaturated carbonyl compounds, are readily converted into -
(trifluoromethyl)allyl thioethers, benzyl ethers, trifluoroacetates,
and azides. A phenyl substituent at the -position to the hydroxyl
haves as a reversible inhibitor in the biosynthesis of
function enhances their reactivity and the ease of SN2 or SN1 sub- isoprenoids.11 A trifluoroprenyl moiety has also been in-
stitutions, whereas a phenyl ring at the -position allows the BF3-
troduced on anti-inflammatory pyrimidopurines and,
again, induces better activity than a prenyl.12 More recent-
mediated synthesis of (trifluoromethyl)indenes. 4-Alkyl-4-meth-
oxy-1-(trifluoromethyl)cyclohexa-2,5-dienols, readily available
ly, it has been reported that the introduction of trifluorom-
from 4-alkylphenols, are easily converted to 4-alkyl(trifluorometh-
ethyl substituents on the meso-positions of porphyrins
yl)benzenes bearing a nucleophilic substituent (MeO, Cl) either on
the ring or the benzylic position.
modifies their absorption spectra in a way which opens
promising opportunities in cancer photodynamic thera-
py.13
Key words: 1-(trifluoromethyl)allyl alcohols, 3-(trifluorometh-
yl)allyl compounds, (trifluoromethyl)arenes, (trifluoromethyl)in-
denes, allylic substitution
Terpenes and isoprenoids constitute a very wide class of
natural compound that often exhibit biological activities.
However, there are a small number of fluorinated iso-
prenoids, in contrast to the place of fluorine in other class-
es of compounds, which might be due to the lack of
suitable reagents for the introduction of 4,4,4-trifluoro-2-
Introduction
Due to the unique properties of fluorine,1 introduction of
this element in organic substrates is well known to in-
crease or modulate their biological properties, especially
as far as target selectivity is concerned.2 Among fluorinat-
ed substituents, the trifluoromethyl group is popular due
to the liphophilicity it brings to organic molecules.3 Sur-
prisingly, however, very few products that contain a trif-
luoromethyl group on a vinylic position have been
reported to exhibit biological activity. An exception is the
preparation of fluorinated analogs of insect juvenile hor-
mone JH-III (the activity of which was dramatically in-
creased by a CF3 group on carbon C-7)4 and that of
cyhalotrin (one of the best selling pyrethroids) and conge-
ners.5
butenyl moieties.
-(Trifluoromethyl)allyl alcohols
should be key tools for this purpose but they are not so
easy to obtain. Three methods for their preparation have
been reported. The first involves the Wittig-type synthesis
of -trifluoromethyl- , -unsaturated esters or ketones
from trifluoroacetylated starting materials, followed by
aluminum hydride reduction,4a,b,6,7b,e,11a,12,14–16 however,
the Wittig step is not totally stereoselective. The second
approach starts from gaseous 1,1,1-trifluoropropyne
(eventually generated in situ from liquid 2-bromo-1,1,1-
trifluoropropene),21 which is condensed with a carbonyl
substrate, the resulting propargylic alcohol being further
reduced in a stereoselective manner with Red-Al [(E)-iso-
mer] or by hydrogenation over Lindlar’s catalyst [(Z)-iso-
mer].17–21 The third route is based on -metalation of
, , -trifluoropropenes, followed by condensation with
an aldehyde.22–26 This method has been also used to pre-
pare -(trifluoromethyl)allyl alcohols from 2-bromo-
1,1,1-trifluoropropene.30 The -(trifluoromethyl)allyl al-
cohols produced have been used in several fruitful trans-
formations such as hydroxyl/halogen exchange followed
by SN2 substitution12,14 or indium-mediated condensation
on carbonyl compounds.27 Several rearrangements of
these substrates have also been studied (Wittig rearrange-
ment,20 Claisen rearrangement and its Johnson, Ireland or
Eschenmoser modifications19,20,23b,24,28,29) as well as osmi-
um-catalyzed dihydroxylation21a and SN2 substitution of
the corresponding acetates.21b All these transformations
are highly stereoselective and lead to polyfunctionalized
To date the most important work on the effect of tri-
flouromethyl substitution has been done on the different
stereoisomers of retinals trifluorinated either at carbons
C-18 or C-19 and/or C-20.6,7 Indeed, fluorine substitution
greatly influences the conformational and spectroscopic
properties of retinal,7a,e and therefore its interaction with
opsin, as it can be seen from in vivo 19F NMR.8 Fluorinat-
ed retinoids also have been reported to be more efficient
on mouse papilloma than non-fluorinated retinoids.9 In a
similar way, introduction of trifluoromethyl groups in car-
otenes enhances their oxidation potential10 and probably
influences their bio-activity. Also it was observed that 3-
SYNTHESIS 2004, No. 3, pp 0456–0465
x
x
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x
x
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0
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Advanced online publication: 26.01.2004
DOI: 10.1055/s-2004-815928; Art ID: E10003SS
© Georg Thieme Verlag Stuttgart · New York

FEATURE ARTICLE Trifluoromethylated Vinylic/Aromatic Compounds from α-(Trifluoromethyl)allyl Alcohols
trifluoromethylated compounds such as polyols or carbo- trimethylsilyl-N-trifluoroacetyl-1,2-aminoalcohols.41
457
hydrates.21a
Thus, we examined the hydroxyl substitution of the result-
ing -(trifluoromethyl)carbinols under different condi-
tions. Since CF3 inhibits the development of a positive
charge at the -position, rearranged products were expect-
ed (Scheme 1).
-(Trifluoromethyl)allyl alcohols are even far less de-
scribed. Nevertheless, they could also be considered as
valuable precursors of trifluoromethylated vinylic prod-
ucts via hydroxyl activation followed by SN2 substitution.
They have been prepared from 2-bromo-1,1,1-
trifluoroacetone31 or (trifluoromethyl)oxirane32 via Wittig
reactions. More recently, reductive titanium-mediated
condensation of aldehydes with 2-bromo- and 2,2,2-tri-
bromo-1,1,1-trifluoroacetone has been reported.33 How-
ever, the regiospecific [1,2]-fluoride-catalyzed addition of
(trifluoromethyl)trimethylsilane to , -unsaturated carbo-
nyl compounds opens a general route to -(trifluorometh-
yl)allyl alcohols.34–36 For our part, we reported several
times on the [1,2]-nucleophilic trifluoromethylation of
, -unsaturated ketones, such as chalcone, di(ben-
zylidene)acetone, or 4-methyl-4-methoxycyclohexa-2,5-
dienone, using different reagents: fluoroform,37 hemiami-
nals of fluoral,38,39 trifluoromethanesulfinamides,40 or O-
Scheme 1 Substitution of -(trifluoromethyl)allyl alcohols.
Biographical Sketches
Sylvie Radix was born in on nucleophilic trifluorome- mium complexes. For two
Villefranche sur Saône thylation in 1998. After a and a half years, she has
(France) in 1971. As a one year postdoctoral stay held a position as a research
former student of the Ecole with Prof. R. Grigg at Leeds assistant in medicinal chem-
Supérieure de Chimie In- University (UK), she spent istry in the Laboratoire de
dustrielle de Lyon, she one year at the University of Chimie Thérapeutique at the
joined Dr. B. R. Langlois’ Geneva in Prof. E. P. Kun- Faculty of Pharmacy of Ly-
group at the University of dig’s group where she on.
Lyon in 1995, where she worked on dearomatization
completed her Ph.D. degree reactions mediated by chro-
Stéphanie Kucharski was from which she graduated in ganofluorine
chemistry.
born in Besançon (France) 1998. During her studies in Now, she is involved in
in 1974. She studied at the chemistry, she spent a one monetics and microchips
Ecole de Chimie, Physique year in Dr B. R. Langlois’ cards.
et Electronique de Lyon laboratory, working on or-
Bernard R. Langlois was In this context, he was in- the University of Lyon
born near Paris (France) in volved in fluorinated aro- where he was appointed as
1947. After receiving his di- matics and heterocycles, first-class Research Direc-
ploma from the ‘Ecole trifluoromethoxy-contain-
tor by the CNRS. There, his
Supérieure de Physique et ing products, trifluoroacetic research group is develop-
Chimie Industrielles de Par- acid derivatives, triflic acid ing new methodologies for
is’ in 1970, he entered the derivatives, and radical tri- the introduction of fluorine-
Rhône-Poulenc Co. where fluoromethylation. In the containing moieties in or-
he worked, in different re- meantime, he obtained a ganic substrates. As far as
search centers (near Paris PhD degree from the Uni- possible, these methodolo-
and Lyon), on organofluo- versity of Lyon in 1984 for gies are illustrated by the
rine chemistry, from bench research on difluorocar- synthesis of potentially bio-
synthesis to development. bene. In 1991, he moved to active compounds.
Synthesis 2004, No. 3, 456–465 © Thieme Stuttgart · New York

458
S. Radix-Large et al.
FEATURE ARTICLE
To our knowledge, only two SN2 substitutions of -(tri- chloride, which was far less chemoselective. This result
fluoromethyl)allyl sulfonates have been reported. The indicates that 1 is much more reactive than its less conju-
first is the quantitative Cu(I)-catalyzed and TMSCl-assist- gated analog 1-phenyl-1-(trifluoromethyl)allyl alcohol
ed reaction of butyl Grignard on (E)-3-benzyloxymethyl- from which a mesylate has been isolated at room temper-
1-(trifluoromethyl)allyl tosylate, which is not completely ature.42 The major isomer (E)-2 has been isolated but ap-
stereoselective.21b The second is the displacement of 1-( - peared to be rather unstable over silica gel and exhibited a
phenylalkyl)-1-(trifluoromethyl)allyl mesylate by azide limited shelf-life (a few days at –18 °C). Nevertheless, its
ions, the stereoselectivity of which is very dependent on E-configuration has been unambiguously assigned by 1H,
the -phenylalkyl substituent.42 As the latter substrate 19F, and 13C NMR, and is in accordance with the litera-
bears a monosubstituted vinyl group, it is not very indica- ture,44 as is the Z-configuration attributed to the minor iso-
tive of the general reactivity of -(trifluoromethyl)allyl mer in the crude product.
sulfonates. Acid-catalyzed reactions of 1-phenyl-1-(triflu-
oromethyl)allyl alcohol have been briefly described
twice. When treated with concentrated sulfuric acid in re-
fluxing acetonitrile, hydrolysis and cyclization strongly
compete with the expected Ritter reaction.42 However, in
warm methanesulfonic acid, cyclization occurs selective-
ly, and 3-(trifluoromethyl)indene is obtained in medium
yield.43a Again, this simple substrate provides limited in-
formation on the reactivity of more substituted allyl alco-
hols. Solvolysis, in acetic or trifluoroacetic acids, of 3-
trifluoromethyl-3-indenyl tosylate, which is a very pecu-
liar allyl sulfonate, has also been described and results in
Scheme 3 Formation of allyl chloride 2 from 1 and TsCl.
the isomerization to 1-trifluoromethyl-3-indenyl tosy-
late.43b
The preparation of 2 from 1 and the Vilsmeier reagent was
also examined. Again, the E-isomer was formed quite ex-
clusively but in a moderate yield (conv. 1: 65%, crude
yield 2: 47%).
Thus, these rare and dispersed elements prompted us to
study the reactivity of the -(trifluoromethyl)allyl alco-
hols we had previously prepared. As we reported before,
1,3-diphenyl-1-(trifluoromethyl)allyl alcohol 1 can be
easily obtained from chalcone and different nucleophilic The high stereoselectivity observed during the SN2 sub-
trifluoromethylating agents (Scheme 2).37–41
stitution of 3 by chloride can be rationalized as follows: as
the CF3 group is surrounded by an intense electrostatic
field which develops strong repulsive interactions with
any -electron or negatively charged nucleophile, 3 prob-
ably adopts, in the transition state, a conformation which
minimizes the repulsions with the electrons of the double
bond and the incoming chloride and leads to the E-isomer
(Scheme 4).
Scheme 2 Nucleophilic trifluoromethylation of chalcone.
Substituent Effects
Initially, 1,3-diphenyl-1-(trifluoromethyl)allyl alcohol (1)
was treated with tosyl chloride at room temperature after
deprotonation with NaH at 0 °C. Surprisingly, the expect-
ed tosylate 3 was not obtained but -(trifluoromethyl)allyl
chloride 2 was quantitatively formed with very high stere-
oselectivity (E/Z, 95:5). This indicates that the chloride
ion generated along with 3 underwent a substitution reac-
tion by a SN2 process (Scheme 3). The less reactive me-
syl chloride led to the same qualitative result as did triflyl
Scheme 4 Stereoselectivity in the formation of 2
Due to its poor stability, 2 was then reacted in situ at room
temperature with sodium n-octanethiolate or benzyl alco-
hol, through a stereospecific SN2 process: allylic products
4a,b were obtained in the same E/Z ratio (95:5) as 2, as in-
Synthesis 2004, No. 3, 456–465 © Thieme Stuttgart · New York

FEATURE ARTICLE Trifluoromethylated Vinylic/Aromatic Compounds from α-(Trifluoromethyl)allyl Alcohols
459
dicated by the coupling constants between fluorine and SN1 character. In order to promote the formation of a cat-
the carbon at the -position,44 measured by 13C NMR ion, 1 was activated with BF3·OEt2 prior to adding a nu-
spectra. No product arising from a SN2 substitution was cleophile. Indeed, the hydroxyl group of 1, as well as that
detected (Scheme 5). In contrast, a complex mixture re- of 1-methyl-1-(trifluoromethyl)cinnamyl alcohol 5, was
sulted from the action of benzylamine.
quantitatively substituted by octanethiol in a stereoselec-
tive SN1 reaction to give 4a and 6 (Scheme 7). The fact
that 1 and 5 exhibited the same reactivity implies that the
phenyl at the -position to CF3 was able to stabilize the
cationic intermediate more efficiently than the phenyl at
the -position. Again, pure E-products were obtained in
3
both cases, as deduced from JCF coupling constants but
1
also from a NOE H-{1H} experiment on compound 6.
The same stereoselectivity was observed with sodium
azide but the yield of 7 was much lower, though the
chemoselectivity was excellent; probably, the azide inter-
acted competitively with boron trifluoride, as suggested
by the limited conversion of 1. Again, such a high stereo-
selectivity can be explained by the conformation of the in-
termediate carbocation which minimizes the repulsive
interactions between the fluorine atoms and the -elec-
trons or the incoming nucleophile (Scheme 8).
Scheme 5 Synthesis of 4a,b from 2.
To help elaborate further on the reactivity, 1 was then re-
acted with anhydrides in order to obtain allylic esters,
which were expected to be more stable than 2. Indeed, the
corresponding acetate was obtained in good yield but did
not undergo nucleophilic substitution with a range of nu-
cleophiles [i-PrNH2, LiN(TMS)2, NaN3, C8H17SH,
CH3SNa, KSCN, C4H9Cu·BF3], even at 80 °C. In contrast,
trifluoroacetic anhydride did not provide the expected tri-
fluoroacetate which was regio- and stereoselectively sub-
stituted, as soon as formed, by the trifluoroacetate anion to
deliver the isomeric -(trifluoromethyl)allyl trifluoroace-
tate 4c in pure E-configuration, as deduced from the 3JCF
coupling constant (Scheme 6).
Scheme 7 BF3-mediated substitution of 1 and 5 by nucleophiles.
Further nucleophiles were then tested; with n-octylamine,
potassium thiocyanate, or sodium diethyl malonate, no
substitution reactions occurred but 1-trifluoromethyl-3-
phenylindene 8a was formed in 20%, 85%, and 35%
yields, respectively. Such a cyclization confirmed the oc-
currence of a carbocation. In order to elucidate the mech-
anism for the formation of 8a, 1 was reacted with
BF3·OEt2 only. In this case, 3-trifluoromethyl-1-phenylin-
dene 8b was isolated in a good yield. Similarly, 8b was
also quantitatively formed from 1 and triflic anhydride
(Scheme 9). Under the action of n-octylamine or upon
Scheme 6 Formation of 4c from 1 and (CF3CO)2O.
Because of the poor nucleophilicity of the trifluoroacetate
anion, it could be suspected that this substitution proceed-
ed through a cationic intermediate and had a pronounced
Scheme 8 Stereoselectivity of the SN1 process.
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460
S. Radix-Large et al.
FEATURE ARTICLE
heating, this compound was isomerized into the more con-
jugated indene 8a (Scheme 9). As previously mentioned,
3-(trifluoromethyl)indene, a simpler analog of 8b, was
prepared formerly, but under more drastic conditions, by
cyclization of 1-phenyl-1-(trifluoromethyl)allyl alcohol
with Brönsted acids such as sulfuric acid in boiling aceto-
nitrile (yield: 7%)42 or warm methanesulfonic acid
(yield: 53%).43
Scheme 11 Aromatization of 9.
Compound 10 obviously resulted from an intramolecular
substitution of the hydroxyl moiety of 9, after its transfor-
mation into a leaving group. Due to the chemoselectivity
observed with mesyl chloride, a concerted intramolecular
SN2 process must be considered. As no chlorine was in-
corporated, this substitution probably occurred after chlo-
ride had diffused away from the molecule. In contrast, the
poorly nucleophilic tosylate anion was incorporated to de-
liver 11 when tosyl chloride was used; it could be suspect-
ed that, in this case, an intermediate carbocation was
generated by solvolysis, after diffusion of the chloride an-
ion. This hypothesis is consistent with the higher sensitiv-
ity of tosylates towards solvolysis, compared with that of
mesylates. The generated cation would then interact either
with TsO– in a solvent cage or with the methoxy substitu-
ent. As far as the Vilsmeier’s reagent was concerned, it
could be suggested that, after reaction of the hydroxyl
group, the generated chloride remained in a close vicinity
of the iminium moiety, because of a possible equilibrium
with a covalent species, and could thus compete with the
methoxy group. These different possibilities are summa-
rized in Scheme 12.
Scheme 9 Formation of 8a and 8b.
Next we turned our attention to cyclic -(trifluorometh-
yl)allyl alcohols since we previously described the tri-
fluoromethylation of 4-methyl-4-methoxycyclohexa-2,5-
dienone. This substrate, easily available from the oxida-
tion of p-cresol with iodine(III) in the presence of metha-
nol, was reacted with trifluoromethane under basic
conditions and afforded the bis-allylic alcohol 9 as a mix-
ture of stereoisomers in which the cis-isomer was prepon-
derant.37 Better yields were obtained with CF3TMS but
without stereoselectivity (Scheme 10).
When 9 was treated with triflic anhydride, 10 was also
formed, as expected, but along with 4-(trifluorometh-
yl)benzyl alcohol (16) and its methyl ether 17
(Scheme 13). As these side-products could be related to
the generation of triflic acid, 9 was also reacted with trif-
luoroacetic acid (used as solvent): again, 16 was isolated
along with its trifluoroacetate 18 (18 was almost the
unique product detected in the crude mixture but was ex-
tensively hydrolyzed during chromatography). In the
same way, stirring 9 in hydroiodic acid led to 4-(trifluo-
romethyl)benzyl iodide 19 (Scheme 13). 1-Trifluoro-
methyl-2-tert-butyl-4-methyl-4-methoxycyclohexa-2,5-
dienol (20), obtained in the same way as 9,37 was also
stirred in trifluoroacetic acid and delivered 3-tert-butyl-4-
Scheme 10 Preparation of alcohol 9.
As 1, cis/trans 9 was reacted with mesyl chloride, tosyl
chloride, and Vilsmeier’s reagent. 4-Methyl-3-meth-
oxy(trifluoromethyl)benzene 10 was selectively obtained
with mesyl chloride and no incorporation of chloride was
observed. In the other cases, 10 remained the major prod-
uct but the side-products depended on the reagent em-
ployed (Scheme 11). Globally, formation of 10 and 12
from p-cresol formally corresponds to a three-step substi-
tution of a phenolic group by trifluoromethyl, along with
additional methoxylation or chlorination.
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FEATURE ARTICLE Trifluoromethylated Vinylic/Aromatic Compounds from α-(Trifluoromethyl)allyl Alcohols
461
Scheme 12 Intra and intermolecular substitutions of 9.
Scheme 14 Mechanism of formation of 18, 19, 22.
Scheme 13 (Trifluoromethyl)benzyl derivatives from 9.
position allows the synthesis of (trifluoromethyl)indenes,
which can lead to interesting Cp-like ligands, as suggested
(trifluoromethyl)benzyl alcohol 21 along with its trifluo-
roacetate 22 (yield 21+22: 57%).
43,45
by Gassman et al.
4-Methyl-4-methoxy-1-(trifluo-
romethyl)cyclohexa-2,5-dienol, as well as its 2-tert-buty-
lated analog, also constitute attractive examples of
As the electron-withdrawing effect of CF3 decreased the
basicity of the hydroxyl function at the -position, the
methoxy group was the most basic site in compound 9 and
was probably protonated selectively; subsequently, meth-
anol was eliminated to provide the quinol methide 23.
Then, the less basic hydroxy group could be activated by
protonation and water substituted, through a SN2 substi-
tution, by the conjugated base of the acid or another nu-
cleophile such as methanol (Scheme 14).
-
(trifluoromethyl)allyl alcohols which allow the mild prep-
aration, in three steps from 4-methylphenol or 2-tert-bu-
tyl-4-methylphenol,
of
4-(trifluoromethyl)toluenes
bearing another substituent (MeO, Cl, I, OCOCF3) on the
ring or at the benzylic position. Formally, these transfor-
mations correspond to a three-step substitution of a phe-
nolic group by trifluoromethyl, along with an additional
‘electrophilic-like’ substitution by a nucleophilic species,
either on an aromatic or benzylic carbon. It would be in-
teresting to optimize this synthetic sequence since no ex-
change of OH for CF3 is known until now and, on the
other hand, few realistic accesses to aromatics bearing
both a methyl group and trifluoromethyl one are available.
Moreover, such a sequence can be probably subjected to a
large synthetic diversity since the methyl group could be
replaced by a longer alkyl chain and methanol could be re-
placed, in the oxidation step, by other nucleophiles such
In conclusion, this study shows that -(trifluoromethyl)al-
lyl alcohols, which are easily available by nucleophilic tri-
fluoromethylation
of
, -unsaturated
carbonyl
compounds, constitute fruitful synthetic tools, especially
for preparing (trifluoromethyl)vinyl moieties or -(tri-
fluoromethyl)allyl thiols, amines, alcohols, ethers, etc….
A phenyl ring at the -position to the hydroxyl function
greatly enhances their reactivity and therefore the ease of
SN2 or SN1 substitutions, whereas a phenyl ring at the -
Synthesis 2004, No. 3, 456–465 © Thieme Stuttgart · New York

462
S. Radix-Large et al.
FEATURE ARTICLE
above-described procedure. The reaction medium was stirred at r.t.
for 10 h then treated as described for 2. Column chromatography
over silica gel (PE) gave 4a (132 mg, 65%) as a colorless oil.
1H NMR (300 MHz): = 0.88 (t, 3 H, J = 6.8 Hz, CH3), 1.20–1.43
(m, 12 H, CH2), 2.32 (t, 2 H, J = 6.8 Hz, CH2S), 4.41 (d, 1 H,
J = 10.9 Hz, CHS), 6.66 (dq, 1 H, J = 10.9, 1.5 Hz, CH=), 7.25–7.44
(m, 10 H, ArH).
13C NMR (50 MHz): = 14.14, 22.70, 28.86, 29.16, 29.19, 29.45,
31.45, 31.86, 46.43 (C4), 123.37 (q, J = 273 Hz, CF3), 127.70,
127.85, 128.63, 129.02, 129.84, 130.96 (q, J = 30.0 Hz, C2),
131.44, 135.75 (q, J = 5.5 Hz, C3), 139.21.
as various alcohols, carboxylic acids, hydrogen bromide
or nitrogen-containing compounds. Finally, ipso-substitu-
tion of the tert-butyl of 22 by an electrophile could be en-
visaged.
Prior to use, THF was distilled over sodium-benzophenone then
stored over 3 Å molecular sieves under N2. Other reagents were
used as received. Starting compounds 1, 5, 9, 20 have been de-
scribed in our previous articles.37–41 TLC analyses were carried out
on Kieselgel 60F 254 deposited on aluminum plates, detection was
carried out by UV (254 nm), phosphomolybdic acid (10% in etha-
nol) or ninhydrine (1% in ethanol). Flash chromatography was per-
formed on silica gel Geduran SI 60. Uncorrected melting points
were determined in capillary tubes. Unless stated otherwise, NMR
spectra were recorded in CDCl3. 1H NMR spectra were recorded at
200MHz or 300 MHz and 13C NMR spectra at 50 or 75 MHz. The
substitution pattern of the different carbons were determined by a
‘DEPT 135’ sequence. 19F NMR spectra were recorded at 188 MHz.
Chemical shifts ( ) are given in ppm with TMS (1H, 13C) or CFCl3
(19F) used as internal references. Coupling constants are given in
Hz. Crude yields were determined by 19F NMR with PhOCF3
19F NMR (188 MHz): = –66.00 (br s).
MS: m/z (%) = 406 (M+·), 261 (M – RS), 221, 191, 183 (100), 133,
69 (CF3), 43, 41.
Anal. Calcd for C24H29F3S: C, 70.9; H, 7.2. Found: C, 70.6; H, 7.4.
(E)-4-Benzyloxy-2,4-diphenyl-1,1,1-trifluoro-2-butene (4b)
The same procedure used was repeated except that the solution of
thiolate was replaced by pure benzyl alcohol (57 L, 0.55 mmol).
Column chromatography with PE–Et2O (98:2) gave 4b (50 mg,
27%) as a colorless oil.
(
F = –58.3 ppm) used as standard. GC was carried out on an appa-
ratus fitted with a semi-capillary column [length: 15 m, : 0.53 mm,
film thickness (DB1): 1 m] and a catharometric detector. Mass
spectrometry, coupled with gas chromatography, was carried out
under electron impact at 70 eV.
1H NMR (300 MHz): = 4.34 (s, 2 H, CH2), 4.80 (d, 1 H, J = 9.2
Hz, CHO), 6.61 (d, 1 H, J = 9.2 Hz, CH=), 7.21–7.38 (m, 15 H,
ArH).
13C NMR (50 MHz): = 70.21 (CH2), 76.82 (C4), 123.10 (q,
J = 273 Hz, CF3), 126.78, 127.75, 127.86, 128.33, 128.37, 128.51,
128.81, 128.89, 129.64, 131.49, 132.50 (q, J = 30.3 Hz, C2), 135.86
(q, J = 5.3 Hz, C3), 137.70, 139.62.
4-Chloro-2,4-diphenyl-1,1,1-trifluoro-2-butene (2)
NaH (4 mmol) was added, as a 60% dispersion in oil (160 mg), to a
solution of 1 (556 mg, 2 mmol) in THF (5 mL), cooled to 0 °C. The
reaction mixture was stirred at 0 °C for 1 h, then p-TsCl (210 mg,
1.1 mmol) was added. Stirring was continued at 0 °C for 30 min
then at r.t. for 24 h. The reaction medium was hydrolyzed with H2O
(5 mL) then extracted with Et2O (3 × 5 mL). The combined organic
phases were washed with brine (5 mL), then H2O (5 mL), and dried
over Na2SO4. After filtration, the solvent was evaporated under vac-
uum at r.t. Column chromatography over silica gel (PE–Et2O,
90:10) gave a pale yellow oil (297 mg, 50%) the NMR analysis of
which indicated the presence of two isomers (E/Z 95:5).
19F NMR (188 MHz): = –66.95 (br s).
Anal. Calcd for C23H19F3O: C, 75.0; H, 5.2. Found: C, 75.2; H, 5.0.
(E)-2,4-Diphenyl-1,1,1-trifluoro-4-trifluoroacetoxy-2-butene
(4c)
NaH (160 mg of a 60% suspension in oil, 4 mmol) was added to a
solution of 1 (556 mg, 2 mmol) in THF (5 mL), cooled to 0 °C. The
resulting mixture was stirred at 0 °C for 1 h then cooled to –10 °C,
then a solution of Tf2O (390 L, 2 mmol) in THF (5 mL) was added
within 15 min. After stirring at r.t. for 3 h, usual work up and col-
umn chromatography with PE–Et2O (80:20) gave 4c (270 mg, 36%)
as an orange oil.
E-Isomer (E)-2
1H NMR (300 MHz): = 5.30 (d, 1 H, J = 10.6 Hz, CHCl), 6.78 (qd,
1 H, J = 10.6, 1.6 Hz, CH=), 7.20–7.35 (m, 7 H, ArH), 7.36–7.51
(m, 3 H, ArH).
1H NMR (300 MHz): d = 6.20 (d, 1 H, J = 9.2 Hz, CHO), 6.67 (qd,
1 H, J = 9.2, 1.6 Hz, CH=), 7.21–7.48 (m, 10 H, ArH).
13C NMR (75 MHz): = 70.31 (C4), 123.17 (q, J = 273 Hz, CF3),
126.21, 131.38, 131.98, (q, J = 30.1 Hz, C2), 136.63 (q, J = 5.3 Hz,
C3), 141.44 (q, J = 1.1 Hz, Carom), 128.60, 128.84, 129.04, 129.68.
19F NMR (188 MHz): = –66.52 (br s).
MS: m/z (%) = 296 (M+·), 262, 261 (M – Cl), 191, 183 (100), 133,
13C NMR (50 MHz):
= 76.35 (C4), 114.5 (q, J = 275 Hz,
CF3CO2), 124.5 (q, J = 286 Hz, CF3), 126.96, 128.80, 129.21,
129.37, 129.62, 130.32, 130.79 (q, J = 5.5 Hz, C3), 135.58 (q,
J = 30.9 Hz, C2), 135.71, 156.22 (q, J = 42.8 Hz, CF3CO).
19F NMR (188 MHz): = –67.65 (br s, CF3), –75.48 (s, CF3CO2).
MS: m/z = 374 (M+·), 305 (M – CF3), 261, 260 (100, M – CF3CO2),
191, 183, 133, 105, 77, 69 (CF3), 51.
115, 77.
Z-Isomer (Z)-2
1H NMR (300 MHz): = 6.05 (d, 1 H, J = 10.6 Hz, CHCl), 6.40 (qd,
1 H, J = 10.6, 1.0 Hz, CH=), 7.20–7.35 (m, 7 H, ArH), 7.36–7.51
(m, 3 H, ArH).
Anal. Calcd for C18H12F6O2: C, 57.8; H, 3.2. Found: C, 57.5; H, 3.4.
1-Phenyl-3-Trifluoromethylindene (8b)
19F NMR (188 MHz): = –57.10 (br s).
To a solution of 1 (139 mg, 0.5 mmol) in CH2Cl2 (1.5 mL), cooled
to 0 °C, was added NaH (42 mg of a 60% suspension in oil, 1
mmol). The resulting mixture was stirred at 0 °C for 1 h then cooled
to –60 °C, then a solution of Tf2O (100 L, 0.6 mmol) in CH2Cl2 (5
mL) was added within 15 minutes. After warming to r.t., the reac-
tion medium was stirred for 24 h, followed by the usual work-up.
Column chromatography with PE–Et2O (95:5) afforded 8b (130
mg, 100%) as a colorless oil.
Because of their limited shelf-life, (E)-2 and (Z)-2 have not been
submitted to elementary analysis.
(E)- 2,4-Diphenyl-4-octylthio-1,1,1-trifluoro-2-butene (4a)
A solution of sodium n-octanethiolate in THF (1 mL) was prepared
from n-octanethiol (95 L, 0.55 mmol) and NaH (44 mg of a 60%
suspension in oil, 1.1 mmol) at 0 °C for 1 h, then added at r.t. to a
solution of 2, prepared in situ from 1 (0.5 mmol) following the
Synthesis 2004, No. 3, 456–465 © Thieme Stuttgart · New York

FEATURE ARTICLE Trifluoromethylated Vinylic/Aromatic Compounds from α-(Trifluoromethyl)allyl Alcohols
463
1H NMR (300 MHz): d = 4.69 (dq, 1 H, J = 2.2, 2.2 Hz, CHPh), 6.99
(dq, 1 H, J = 2.2, 2.2 Hz, CH=), 7.06 (m, 2 H, ArH), 7.22–7.37 (m,
6 H, ArH), 7.54 (dq, 1 H, J = 7.7, 1.1 Hz, H4). 13C NMR (50 MHz):
d = 53.40 (C1), 120.80 (C4), 122.39 (q, J = 270 Hz, CF3), 124.43
(C7), 126.85 (C6), 127.37 (C5), 127.48, 127.88, 128.97, 134.50 (q,
J = 34 Hz, C3), 136.94, 138.06 (C3a), 140.80 (q, J = 5 Hz, C2),
147.89.
3-Phenyl-1-(trifluoromethyl)indene (8a)
From 1, BF3·Et2O, and KSCN (194 mg, 2.0 mmol). Reaction time:
3 h. Column chromatography with PE–Et2O (95:5) gave 8a (111
mg, 85%) as a white solid; mp 49–51 °C.
1H NMR (200 MHz): d = 4.27 (qd, 1 H, J = 9.3, 2.1 Hz, H1), 6.45
(d, 1 H, J = 2.2 Hz, H2), 7.30–7.72 (m, 9 H, ArH).
13C NMR (50 MHz): = 52.63 (q, J = 29 Hz, C1), 121.17 (C4),
124.69 (q, J = 2.9 Hz, C2), 124.82 (q, J = 1.5 Hz, C7), 126.12 (q,
J = 278 Hz, CF3), 126.32 (C6), 127.74, 128.42 (C5), 128.51,
128.89, 134.54, 138.68 (q, J = 2.0 Hz, C7a), 144.14 (C3a), 149.32
(C3).
19F NMR (188 MHz): = –64.54 (br s).
MS: m/z = 260 (100, M+·), 240, 192, 191 (100, M – CF3), 165, 94,
82.
Anal. Calcd for C16H11F3: C, 73.8; H, 4.3. Found: C, 73.6; H, 4.4.
19F NMR (188 MHz): = –67.80 (d, J = 9.3 Hz).
MS: m/z = 260 (M+·), 191, 165, 95, 83.
BF3-Mediated Substitution of 1 and 5 by Nucleophiles; General
Procedure
To a solution of 1 (139 mg, 0.5 mmol) or 5 (108 mg, 0.5 mmol) in
CH2Cl2 (2 mL, HPLC grade), cooled to –78 °C, was added
BF3·Et2O (65 L, 0.5 mmol). After stirring for 15 min at –78 °C, the
nucleophile was added and stirring was continued at the same tem-
perature for 15 min before warming to r.t. Unless stated otherwise,
the reaction mixture was stirred at r.t. for 24 h, followed by the usual
work-up. The organic residue was purified by column chromatogra-
phy.
Anal. Calcd for C16H11F3: C, 73.8; H, 4.3. Found: C, 74.0; H, 4.2.
1-Phenyl-3-(Trifluoromethyl)indene (8b)
From 1 and BF3·Et2O. Reaction time: 4 h. Column chromatography
with PE–Et2O (95:5) gave 8b (81 mg 62%) as a colorless oil.
Isomerization of 8b into 8a
Octylamine (260 mg, 1 mmol) was added at r.t. to a solution of 8b
(260 mg, 1 mmol) in CH2Cl2 (3 mL, HPLC grade). The mixture was
stirred for 1 h then underwent the usual work-up procedure. Column
chromatography with PE–Et2O (95:5) afforded 8a (104 mg, 40%).
(E)-2,4-Diphenyl-4-octylthio-1,1,1-trifluoro-2-butene (4a)
From 1, BF3·Et2O, and n-octanethiol (95 L, 0.55 mmol). Column
chromatography with PE gave 4a (203 mg, 100%) as a colorless oil.
3-Methoxy-4-methyl(trifluoromethyl)benzene (10)
Reaction of 9 and Methanesulfonyl Chloride
Compound 9 (208 mg, 1 mmol) was treated with MsCl for 6 h at r.t.,
following the procedure used for the synthesis of 2 from 1 and p-
TsCl. Column chromatography with PE–Et2O (80:20) gave 10 (95
mg, 50%) as a colorless oil.
1H NMR (300 MHz): = 2.25 (s, 3 H, CH3), 3.85 (s, 3 H, OCH3),
6.85 (d, 1 H, J = 8.5 Hz, H5), 7,37 (q, 1 H, J = 0.7 Hz, H2), 7.42 (dq,
1 H, J = 8.5, 0.7 Hz, H6).
13C NMR (75 MHz): = 16.21 (CH3), 55.47 (OCH3), 109.47 (C5),
122.34 (q, J = 32.3 Hz, C1), 124.33 (q, J = 4.0 Hz, C2), 124.60 (q,
J = 271 Hz, CF3), 127.33 (C4), 127.44 (q, J = 3.5 Hz, C6), 160.17
(C3).
(E)-4-Azido-2,4-diphenyl-1,1,1-trifluoro-2-butene (7)
From 1, BF3·Et2O, and sodium azide (130 mg, 2.0 mmol). Column
chromatography with PE–Et2O (90:10) gave 7 (33 mg, 22%) as a
yellow oil.
1H NMR (300 MHz): = 5.02 (d, 1 H, J = 9.9 Hz, CHN), 6.57 (dq,
1 H, J = 9.9, 1.5 Hz, CH=), 7.25–7.29 (m, 4 H, ArH), 7.39–7.50 (m,
6 H, ArH).
13C NMR (50 MHz): = 61.93 (C4), 122.84 (q, J = 274 Hz, CF3),
126.79, 128.73, 128.83, 129.10, 129.35, 129.75, 130.61, 132.68 (q,
J = 5.3 Hz, C3), 134.20 (q, J = 29.8 Hz, C2), 137.17.
19F NMR (188 MHz): = –67.01 (br s).
MS: m/z = 303 (M+·), 275 (M – N2), 274, 261 (M – N3), 206, 192,
19F NMR (188 MHz): = –61.46 (s).
MS: m/z = 190 (100%, M+·), 175 (M – CH3), 159 (M – OCH3), 145,
183 (100), 151, 133, 103, 77, 51.
Anal. Calcd for C16H12F3N3: C, 63.4; H, 4.0; N, 13.9 Found: C, 63.1;
H, 4.2; N, 14.1.
121 (M – CF3), 109, 91, 77.
Anal. Calcd for C9H9F3O: C, 56.8; H, 4.8. Found: C, 57.0; H, 4.5.
(E)-2-Methyl-4-octylthio-4-phenyl-1,1,1-trifluoro-2-butene (6)
From 5, BF3·Et2O, and n-octanethiol (95 L, 0.55 mmol). Column
chromatography with PE–Et2O, (80:20) gave 6 (172 mg, 100%) as
a colorless oil.
2-Methyl-5-(trifluoromethyl)phenyl para-Toluenesulfonate
(11)
Reaction of 9 with p-TsCl
1H NMR (300 MHz): = 0.88 (t, 3 H, J = 6.6 Hz, CH3CH2), 1.10–
1.45 (m, 12 H, CH2), 1.90 (s, 3 H, CH3C=), 2.38 (t, 2 H, J = 7.4 Hz,
CH2S), 4.70 (d, 1 H, J = 10.3 Hz, CHS), 6.34 (dq, 1 H, J = 10.3, 1.5
Hz, CH=), 7.21–7.37 (m, 5 H, ArH).
13C NMR (50 MHz): = 10.95 (q, J = 1.1 Hz, CH3C=), 14.12
(CH3CH2), 22.74, 24.69, 29.16, 29.23, 29.30, 31.92, 34.18, 45.96
(C4), 124.07 (q, J = 273 Hz, CF3), 125.63 (q, J = 30 Hz, C2),
127.76, 128.88, 133.25 (q, J = 6.0 Hz, C3), 139.53.
Compound 9 (208 mg, 1 mmol) was treated with p-TsCl for 3 h in
refluxing THF, following the procedure used for the synthesis of 2
from 1 and p-TsCl. Column chromatography with PE–Et2O (80:20)
allowed the separation of 10 from 11 and gave 11 (99 mg, 30%) as
a white solid.
1H NMR (300 MHz): = 2.17 (s, 3 H, CH3), 2.46 (s, 3 H, CH3), 7.17
(s, 1 H, H6), 7.26–7.41 (m, 4 H, H3,4,2 ,6 ), 7.65 (d, 2 H, J = 8.1 Hz,
H3 ,5 ).
13C NMR (50 MHz): = 16.50 (CH3), 21.72 (CH3), 119.71 (q,
J = 3.8 Hz, C6), 123.37 (q, J = 272 Hz, CF3), 123.66 (q, J = 3.8 Hz,
C4), 128.48 (C3 ), 128.97 (q, J = 33 Hz, C5), 130.01 (C2 ), 132.12
(C3), 132.60 (C2), 136.26 (C4 ), 145.98 (C1 ), 148.15 (C1).
19F NMR (188 MHz): = –69.78 (br s).
1
NOE H-{1H}: irradiation of methyl group ( =1.90) enhanced
(+3.5%) the signal corresponding to the proton on C-4 ( = 4.70).
Anal. Calcd for C19H27F3S: C, 66.2; H, 7.9 Found: C, 66.4; H, 7.8.
19F NMR (188 MHz): = –63.08 (s).
Anal. Calcd for C15H13F3O3S: C, 54.5; H, 4.0. Found: C, 54.1; H,
4.2.
Synthesis 2004, No. 3, 456–465 © Thieme Stuttgart · New York

464
S. Radix-Large et al.
FEATURE ARTICLE
Reaction of 9 with the Vilsmeier’s Reagent
19F NMR (188 MHz): = –62.90 (s).
Compound 9 (208 mg, 1 mmol) was treated with chloromethylene-
N,N-dimethyliminium chloride for 24 h at r.t., following the proce-
dure used for the synthesis of 2 from 1 and p-TsCl. Column chro-
matography with PE–Et2O (80:20) gave 10 along with an
inseparable mixture of 3 chlorinated products (12, 13, 14) which
were characterized by 19F NMR and gas chromatography coupled
with mass spectroscopy.
MS: m/z = 176 (M+·), 157 (M – F), 145 (M – CH2OH), 127, 107
(M – CF3), 79 (100), 77, 69 (CF3), 50.
These data were in complete accordance with those of a commercial
authentic sample (from Aldrich Co.) and elementary analysis has
not been carried out.
3-tert-Butyl-4-(trifluoromethyl)benzyl Alcohol (21)
Compound 20 was reacted with CF3CO2H as described above. Col-
umn chromatography with PE–Et2O (80:20) followed by Et2O
(100%) gave 21 (57 mg, 40%) as a yellowish oil.
1H NMR (300 MHz): = 1.46 [s, 9 H, C(CH3)3], 2.20 (br s, 1 H,
OH), 4.74 (s, 2 H, CH2), 7.29 (d, 1 H, J = 8.1 Hz, H6), 7.63 (s, 1 H,
H2), 7,71 (d, 1 H, J = 8.1 Hz, H5).
3-Chloro-4-methyl(trifluoromethyl)benzene (12)
19F NMR (188 MHz): = –63.12 (s).
MS: m/z =196 (M+·), 194 (M+·), 177 (M – F), 175 (M – F), 159 (100,
M – Cl), 127 (M – F3), 125 (M – CF3), 89.
2-Chloro-1-methoxy-1-methyl-4-trifluoromethyl-3,5-cyclo-
13C NMR (50 MHz): = 32.06 [q, J = 3.4 Hz, C(CH3)3], 36.64
(CMe3), 64.75 (CH2), 124.07 (C6), 125.16 (q, J = 274 Hz, CF3),
127.02 (C2), 127.38 (q, J = 30.5 Hz, C4), 128.74 (q, J = 7.4 Hz,
C5), 144.19, C3), 149.63 (q, J = 1.6 Hz, C1).
hexadiene (13)
2 diastereomers.
19F NMR (188 MHz): = –68.73 (s).
MS: m/z = 226 (M+·), 191 (M – Cl), 175, 159, 91, 77, 43 (100).
19F NMR (188 MHz): = –53.27 (s).
MS: m/z = 232 (M+·), 217 (M – CH3), 197, 147, 91, 77, 57, 41 (100),
29.
1,4-Dichloro-2-methyl-5-trifluoromethyl-2,5-cyclohexadiene
(14)
2 diastereomers.
19F NMR (188 MHz): = –76.73 (s), –77.34 (s).
Anal. Calcd for C12H15F3O: C, 62.1; H, 6.5. Found: C, 61.9; H, 6.8.
MS: m/z = 230 (M+·), 213 (M – F), 211 (M – F), 197 (M – Cl), 195
4-(Trifluoromethyl)benzyl Iodide (19)
Compound 9 was reacted with HI as described above. Column chro-
matography with PE–Et2O (80:20) gave 19 (100 mg, 35%) as a red-
dish oil.
1H NMR (200 MHz): = 4.47 (s, 2 H, CH2), 7.49 (d, 2 H, J = 8.4
Hz, H2,6), 7.57 (d, 2 H, J = 8.4 Hz, H3,5).
13C NMR (75 MHz): = 33.50 (CH2), 124.04 (q, J = 296 Hz, CF3),
125.79 (q, J = 3.8 Hz, C3,5), 129.03 (C2,6), 130.02 (q, J = 20.1 Hz,
C4), 143.27 (q, J = 1.3 Hz, C1).
(M – Cl), 159, 91 (100).
4-(Trifluoromethyl)benzyl Derivatives; General Procedure
Trifluoroacetic acid or 57% aqueous hydroiodic acid (0.5 mL) was
added to 9 or 20 (1 mmol) at r.t. The reaction medium was stirred at
this temperature until the substrate was completely consumed as in-
dicated by GPC. After addition of Et2O (10 mL), the crude medium
was neutralized with 8% aqueous NaHCO3. After decantation, the
aqueous phase was extracted again with Et2O (3 × 5 mL). The com-
bined organic phases were washed with brine (5 mL) then H2O (5
mL), and dried over Na2SO4. After evaporation of the solvent at
room temperature under reduced pressure, the residue was separat-
ed and purified over silica gel.
19F NMR (188 MHz): = –63.06 (s).
MS: m/z 286 (M+·), 159 (100, M – I), 140, 109, 89.
Anal. Calcd for C8H6F3I: C, 33.6; H, 2.1. Found: C, 33.3; H, 2.3.
Reaction of 9 with Trifluoroacetic Acid
Acknowledgment
Column chromatography with PE–Et2O (80:20) gave 18 (57 mg,
21%) as a colorless oil and further elution with Et2O (100%) gave
16 (130 mg, 75%) as a yellowish oil.
One of us (S.L.-R.) thanks the Rhodia Co. for financial support.
4-(Trifluoromethyl)benzyl Trifluoroacetate (18)
1H NMR (300 MHz): = 5.41 (s, 2 H, CH2), 7.51 (d, 2 H, J = 8.1
Hz, H2,6), 7.67 (d, 2 H, J = 8.1 Hz, H3,5).
References
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13C NMR (75 MHz): = 68.41 (CH2), 114.47 (q, J = 285 Hz,
CF3CO2), 123.82 (q, J = 272 Hz, CF3), 125.93 (q, J = 3.7 Hz, C3,5),
128.62 (C2,6), 131.46 (q, J = 32.7 Hz, C4), 137.13 (q, J = 0.9 Hz,
C1), 157.27 (q, J = 42.7 Hz, CF3CO2).
19F NMR (188 MHz): = –63.30 (s, CF3), –75.30 (s, CF3CO2).
MS: m/z = 272 (M+·), 253 (M – F), 203 (M – CF3), 175, 159 (100),
145, 109, 89, 69 (CF3), 63.
Anal. Calcd for C10H6F6O2: C, 44.1; H, 2.2. Found: C, 44.3; H, 2.4.
4-(Trifluoromethyl)benzyl Alcohol (16)
1H NMR (300 MHz): = 2.13 (br s, 1 H, OH), 4.75 (s, 2 H, CH2),
7.46 (d, 2 H, J = 7.9 Hz, H2,6), 7,61 (d, 2 H, J = 7.9 Hz, H3,5).
13C NMR (50 MHz): = 64.46 (CH2), 123.85 (q, J = 270 Hz, CF3),
125.48 (q, J = 3.8 Hz, C3,5), 126.86 (C2,6), 129.81 (q, J = 32.3 Hz,
C4), 144.78 (C1).
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FEATURE ARTICLE Trifluoromethylated Vinylic/Aromatic Compounds from α-(Trifluoromethyl)allyl Alcohols
465
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