An efficient access to (Z)-β-fluoroallyl alcohols based on the two carbon homologation of aromatic aldehydes by Horner-Wadsworth-Emmons reaction with 2-(diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S-ethyl ester followed by reduction with sodium borohy

Article abstract of DOI:10.1016/j.tet.2012.02.039

We describe a biomimetic approach to (Z)-β-fluoroallyl alcohols based on the two carbon homologation of aromatic aldehydes to α-fluorocinnamic thioesters by Horner-Wadsworth-Emmons reaction with 2-(diethoxyphosphinyl)-2- fluoro-ethanethioic acid, S-ethyl

Full text of DOI:10.1016/j.tet.2012.02.039

Tetrahedron 68 (2012) 3225e3230
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An efficient access to (Z)-b-fluoroallyl alcohols based on the two carbon
homologation of aromatic aldehydes by HornereWadswortheEmmons reaction
with 2-(diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S-ethyl ester followed by
reduction with sodium borohydride
,
,
Mohammed Kajjout a, Rajae Zemmouri a, Said Eddarir a b, Christian Rolando a
*
a
ꢀ
ꢁ
ꢀ
Universite de Lille 1, Sciences et Technologies, USR CNRS 3290 Miniaturisation pour la synthese, l’Analyse & la Proteomique, 59655 Villeneuve d’Ascq Cedex, France
b
ꢀ
ꢀ
ꢀ
Universite de Cadi Ayyad, Faculte des Sciences et Techniques Gueliz, BP 549 Marrakech, Morocco
a r t i c l e i n f o
a b s t r a c t
Article history:
We describe a biomimetic approach to (Z)-b-fluoroallyl alcohols based on the two carbon homologation
Received 20 November 2011
Received in revised form 12 February 2012
Accepted 14 February 2012
Available online 22 February 2012
of aromatic aldehydes to
(diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S-ethyl ester, followed by reduction with sodium bo-
rohydride in mild conditions. The -fluorothioesters were obtained in a good yield by condensing the
a-fluorocinnamic thioesters by HornereWadswortheEmmons reaction with 2-
a
aldehydes with the lithium anion of 2-(diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S-ethyl ester in
THF at ꢀ78 ꢁC. The (E,Z)-
a
-fluorocinnamic thioester mixtures were then cleanly reduced with double
Keywords:
bond isomerisation to the corresponding (Z)-
b
-fluoroallyl alcohols by NaBH4 at room temperature. This
(Z)-
HornereWadswortheEmmons
-Fluorothioesters
b-Fluoroallyl alcohols
methodology may be applied to highly functionalized aldehydes as exemplified by the straightforward
access to (Z)-
b
-fluoroconiferin, a strong inhibitor of lignin polymerization from O-glucosylated vanillin.
Ó 2012 Elsevier Ltd. All rights reserved.
a
NaBH4 reduction
Fluroconiferin
1. Introduction
coniferyl alcohol (4-(3-hydroxy-1-propenyl)-2-methoxyphenol),
nature uses as intermediate the coenzyme A thioester of the corre-
Fluorinated organic compounds are known to have interesting
biological activities.1 The chemistry of fluorinated organic molecules
is unique because of the properties of fluorine, such as strong elec-
tronegativity, small size and the low polarisability of the CeF bond.
These properties of the fluorine atom can havea considerable impact
on the behaviorof a molecule in a biological environment. Indeed, an
increasing number of drugs contain fluorine, the presence of which
often is of major importance to their activity.2 2-Fluoropropenol
derivatives are a family of fluorinated compounds that have re-
ceived a considerable attention.3 The 2-fluoropropenol motif is the
key structure of several biologically active compounds.4 2-
Fluoropropenols are generally obtained from 2-fluoropropenic
acid ester by WittigeHorner condensation with trialkythyl-
fluorophosponacetate followed by reduction with a strong reducing
reagent like DIBAL-H5 or LiAlH4.6 Sodium borohydride may also be
used but in harsh conditions, typically NaBH4 (7.4 equiv) in presence
of LiCl (10 equiv) in glyme (80 ꢁC, 18 h).7 When applied to complex
molecule containing other ester functions these conditions lead to
complex mixtures. During the biosynthesis of lignin monomers like
sponding cinnamic acid, which is first reduced into aldehyde by
cinnamoyl-CoA reductase (CCR) and then the aldehyde to the alco-
hol by cinnanyl alcohol dehydrogenase (CAD).8 Indeed, thioesters
are much more easily reduced than their ester homologues and are
reduced by sodium borohydride to the corresponding alcohol at
room temperature.9 In the 3-phenyl-propen-1-ol series, the re-
quiredcinnamic acid thioester may be obtained either bycouplingof
a thiol with an activated form of cinnamic acid, like, for example, in
the synthesis of caffeoyl coenzyme A thioester10 or from the corre-
sponding benzaldehyde using a two carbon homologation. The lat-
ter is based on the HornereWadswortheEmmons reaction, which
was described almost simultaneously by three groups, Coutrot
et al.,11a Liu et al.11b and Schaumann et al.11c We present a new bio-
mimetic synthesis of (Z)- -fluoroallyl alcohols based on the prepa-
b
ration of -fluoro-a,b-unsaturated thioesters using 2-
a
(diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S-ethyl ester as
a new HornereWadswortheEmmons reagent, followed by the re-
duction of these thioesters to the corresponding (Z)-
alcohols by NaBH4 in ethanol at room temperature. This method-
ology enabled us to synthesize the glucoside of -fluoroconiferyl
alcohol, (Z)- -fluoroconiferin, a strong inhibitor of lignin polymeri-
zation, in three steps.7
b-fluoroallyl
b
b
* Corresponding author. Tel.: þ33 (0) 320434977; fax: þ33 (0) 320336136;
e-mail address: christian.rolando@univ-lille1.fr (C. Rolando).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.02.039

3226
M. Kajjout et al. / Tetrahedron 68 (2012) 3225e3230
2. Results and discussion
well known for its sensitivity to reaction parameters. As reported
above, the benzaldehyde gives a nearly pure E product whereas
crotonaldehyde affords the reverse Z geometry.17 So it is not sur-
prising that the situation is more contrasted with benzaldehyde-
bearing substituents (Table 1, entries bef). A recent paper reports
Only a few reports described the preparation of
a-fluoro-a,b-
unsaturated thioesters contrary to their non-fluorinated homo-
logues.11,12 Ethyl (Z)-2-fluorocinnamothioates are obtained by
condensing 3,3-bis(methylthio)-2-fluoropropenal with phenyl-
magnesium bromide followed by the allylic rearrangement of the
1,1-bis(methylthio)-2-fluoro-3-phenylprop-1-en-3 thus obtained
using mercuric chloride in acetonitrile/water.13 In their approach,
Coutrot et al.11a prepared a family of 2-[bis(1-methylethoxy)phos-
phinyl]-ethanethioic acid, S-propyl ester substituted in the two
position by alkyl groups, aromatic groups and by halogens (chlo-
rine, fluorine). Surprisingly, this family of reagents with bulky
substituents on the phosphoryl group and on the thioester gave
poor yields in the HornereWadswortheEmmons condensation
step and no example was described with the 2-fluorinated Hor-
nereWadswortheEmmons reagent. In our approach, we developed
than the reaction Hammett constant
r for a non-fluorinated Hor-
nereWadswortheEmmons reagent is positive in the 2.7e3.6 range
showing that the benzaldehyde-bearing electrodonating sub-
stituents are reacting faster.18 Unfortunately, to the best of our
knowledge there is no equivalent report for the stereochemistry.19
No clear trend with the substitution parameters can be seen in our
data. As a result, no further attempt was made to control the ste-
reochemistry as the a,b-unsaturated a-fluorothioesters 6aef were
isomerized during the next reduction step to their Z isomer. The
HornereWadswortheEmmons step works both with non-
substituted (Table 1, entry a), slightly or strongly electroattractive
groups (Table 1, entry b and c, respectively), electrodonating group
(Table 1, entry e) or functionalized groups (Table 1, entry f).
a
novel HornereWadswortheEmmons reagent: 2-(diethox-
yphosphinyl)-2-fluoro-ethanethioic acid, S-ethyl ester with
smaller substituents both on the acid S-thioester and on the
phosphoryl group, for the preparation of -fluoro- -unsaturated
thioesters. Coupling of 4 with an aromatic aldehydes would pro-
vide an efficient method to access a variety of -fluoro- -un-
4
O
O
P
EtO
EtO
a
a,b
F
SEt
R"
R'''
R''
R'''
O
O
F
a
a,b
4
R'
R'
SEt
saturated thioesters. 2-(Diethoxyphosphinyl)-2-fluoro-ethanethioic
acid, S-ethyl ester 4 was obtained in three steps as described in
Scheme 1. Foremost 2-(diethoxyphosphinyl)-2-fluoro-acetic acid 2
was prepared by the saponification of 2-(diethoxyphosphinyl)-2-
fluoro-acetic acid, ethyl ester 1 with sodium hydroxide in etha-
nol/water.14 Direct conversion of carboxylic acid 2 into acid chlo-
ride 3 was achieved in quantitative yields by treatment of 2 with
thionyl chloride in dichloromethane.15 Finally, the reaction be-
tween the carboxylic acid chloride 3 and ethanethiol in the pres-
ence of triethylamine in dichloromethane gave the desired 2-
(diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S-ethyl ester 4.
Crude acid chloride 3 was used without further purification for this
step because this compound decomposed partially during distilla-
tion. 2-(Diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S-ethyl
ester 4 was obtained in a 43% yield from the commercially available
2-(diethoxyphosphinyl)-2-fluoro-acetic acid, ethyl ester 1.
BuLi/-78 °C, THF
R
R
6
5
Scheme 2. Synthesis of a,b-unsaturated a-fluorothioesters 6aef.
Table 1
Yields of
the corresponding aldehydes
a
-fluorothioesters 6aef from HornereWadswortheEmmons reaction of
Entry
R
R0
R00
R000
(E/Z)b
Yield (%)
a
b
c
d
e
f
H
H
H
H
H
MeO
H
F
NO2
H
H
H
H
Br
H
H
H
H
H
H
CH3
H
90/10
0/100
60/40
0/100
100/0
80/20
80
91
66
64
81
73
H
GluOa
a
GluO¼2,3,4,6-tetra-O-acetyl-
b-D-glucopyranosyl.
b
From 1H and 19F NMR.
O
O
O
O
P
O
P
EtO
EtO
EtO
EtO
NaOH, H2O
SOCl2
The second step of this work is the reduction of the (E/Z)-
fluorocinnamic acid thioesters 6aef mixture to the corresponding
(Z)- -fluoroallyl alcohols 7aef. Thioesters could be reduced by
a-
OH
OEt
EtOH
73%
F
1
F
2
CH2Cl2, reflux
95%
b
various reagents directly to the corresponding aldehydes. Thio-
esters are reduced in aldehydes in mild conditions with trie-
thylsilane in the presence of palladium on carbon catalyst (Pd/C
2.0e5.0 mol %),20aec and the reaction may be performed with
a lower catalytic amount of catalyst (0.5e1.0 mol %).20d Aldehydes
could also be obtained from the reduction of thioesters with dii-
sopropylaluminium hydride in dichloromethane at ꢀ55 ꢁC20e or in
toluene at ꢀ78 ꢁC.20f However, the reduction of thioesters to al-
cohols is less documented than their reduction to aldehydes. As in
the case of esters, LiAlH4 in excess affords the alcohol but this re-
agent is not compatible with our objective of a mild reduc-
tion.21a,21b Benzenecarbothioic acid and S-phenyl esters are
reduced to benzyl alcohol using nickel boride, generated in situ
from nickel chloride hexahydrate and sodium borohydride in
methanol/THF.21c Thioesters are also cleanly reduced to alcohol by
zinc borohydride.21d However, the best synthetic approach seemed
us the simplest, the reduction of the thiol ester by NaBH4 at room
temperature, which is compatible with ester, nitrile and epoxyde
O
O
P
O
P
EtO
EtO
EtO
EtO
NEt3, EtSH
Cl
SEt
CH2Cl2
62%
F
3
F
4
Scheme 1. Synthesis of 2-(diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S-ethyl
ester.
The HornereWadswortheEmmons condensation between
compound 4 and the aromatics aldehydes 5aef in presence of n-
butyllithium at ꢀ78 ꢁC gave the
a,b-unsaturated a-fluorothioesters
6aef in good yields (64e91%) as a mixture of E, Z isomers (Scheme
2). With benzaldehyde 5a, the HornereWadswortheEmmons re-
agent 4 gave a 90/10 mixture of E/Z isomers (Table 1, entry a) in
agreement with the reactivity previously described for 2-(dieth-
oxyphosphinyl)-2-fluoro-acetic acid, ethyl ester 1 in THF using n-
BuLi as a base at ꢀ78 ꢁC.16 The WadswortheEmmons reagent 1 is
functions.9 To the best of our knowledge, for the reduction of
fluoro- -unsaturated thioesters, only the reduction of methyl (Z)-
a-
a,b

M. Kajjout et al. / Tetrahedron 68 (2012) 3225e3230
3227
3-(40-imidazolyl)-2-fluorothioacrylate to (Z)-2-fluoro-3-(40-imida-
zolyl)-2-propenol with NaBH4 in a fair yield (51%) has been de-
scribed in literature.13 We chose to work under the same mild
conditions using NaBH4 in ethanol at room temperature for the
sodium methylate afforded (Z)-
b
-fluoroconiferin 8 in quantitative
yield.26 From O-glucosylated vanillin the (Z)-
b-fluoroconiferin 8 was
obtained in a 57% yield.
AcO
reduction of
The results of the NaBH4 reductions of
a
-fluoro-
a
,
b
-unsaturated thioesters 6aef (Scheme 3).
-fluoro- -unsaturated
a
a,b
AcO
O
thioesters 6aef to the corresponding fluoroallyl alcohols 7aef are
listed in Table 2.
O
AcO
O
R'''
R''
F
O
R''
R'''
OH
F
OAc
5f
MeO
NaBH4
O
O
P
R'
SEt
R'
EtO
EtO
BuLi, THF, -78 °C
RT, EtOH
SEt
O
6, E/Z
7, Z
73 %
AcO
R
R
4
F
Scheme 3. Reduction of a-fluorothioesters 6aef by sodium borohydride.
AcO
O
F
Table 2
Reduction of 6aef with NaBH4/EtOH
AcO
AcO
O
SEt
OAc
6f
MeO
7
R
R0
R00
R000
Yield (%)
a
b
c
d
e
f
H
H
H
H
H
MeO
H
F
NO2
H
H
H
H
H
Br
H
H
H
H
H
H
CH3
H
83
84
86
82
90
78
78% NaBH4
AcO
AcO
O
F
OH
O
GluO
OAc
7f
MeO
A careful inspection of 1H and 19F NMR spectra shows the
presence of one isomer with Z geometry. So, starting from an E/Z
mixture of -fluoro- -unsaturated thioesters 6aee, the reactions
proceeded successfully with complete isomerization of the double
bond to give the corresponding stereochemically pure (Z)- -fluo-
roallyl alcohols 7aef in good yields (78e90%) and in a convergent
way. (E)- -Fluorocinnamic esters may be isomerized to the more
stable (Z)-isomers using an electrophilic reagent like bromine or
iodine.7,22 (E)-
-Fluorocinnamic esters are not so easily isomerized
quant. yield NaOMe / MeOH
HO
a
a,b
HO
HO
b
O
F
OH
a
O
OH
8
MeO
a
by nucleophilic reagents since they may be reduced without loss of
stereochemistry by DIBAL-H to the corresponding alcohol. But
according to the DIBAL-H ester reduction mechanism, the free al-
dehyde is not present in the solution when an excess of DIBAL-H is
used, because the reduction of the aldehyde is faster than the re-
duction of the initial ester.23 So we may guess that the isomeriza-
tion is produced by the reversible Michael addition of the
ethylthiolate24 formed during the reduction of the thioester to the
(Z)-ß-fluoro-coniferin
Scheme 5. Synthesis of (Z)-b-fluoroconiferin 8.
3. Conclusion
We recently presented a biomimetic strategy for the synthesis of
(Z)- -fluoroallyl alcohols based on the palladium-catalyzed for-
mylation by carbon monoxide of -bromo- -fluoroolefins obtained
by WittigeBurton reaction, to obtain -fluoro conjugated alde-
hydes, which were then reduced to the corresponding alcohols.27
The new synthesis of (Z)- -fluoroallyl alcohols we present here
b
intermediate free (E)-
a
-fluorocinnamic aldehyde (Scheme 4).
a
a
a
SEt
H
O
O
b
F
F
based on the HornereWadswortheEmmons reaction of benzalde-
hyde with 2-(diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S-
ethyl ester 4, followed by reduction with NaBH4, is even simpler
since it involves only two steps, compared to three from the same
+
NaBH4
+
NaSEt
H
O
F
F
H
O
C
precursor using the formylation by carbon monoxide of
-fluoroolefins approach. All the steps are compatible with highly
functionalized molecules. This straightfoward synthesis allowed us
to access of pure (Z)- -fluoroconiferin 8, a strong inhibitor of lignin
polymerization.7 The (Z)-
-fluoroconiferin 8 we obtained will be
a-bromo-
a
SEt
Scheme 4. Proposed isomerization mechanism during the reduction of
unsaturated thioesters 6aee E/Z mixture to pure (Z)- -fluoroallyl alcohols 7aef.
a
-fluoro-
a
,
b-
b
b
b
used to further understand the inhibition of lignin biosynthesis in
plantlets growing in an artificial medium.28
This methodology gave a new and straightforward access to (Z)-
b-
fluoroconiferin (Scheme 5). The synthesis was performed in three
steps starting from O-glucosyl-vanillin 5f.25 The corresponding
a-
4. Experimental
4.1. General
fluoroester 6f was obtained using the HornereWadswortheEmmons
reagent, 2-(diethoxyphosphinyl)2-fluoro-ethanethioic acid, S-ethyl
ester 4, deprotonated by n-BuLi at ꢀ78 ꢁC in THF. The reduction of 6f
intoalcohol7fwasaccomplishedbysodiumborohydrideinethanol.A
final deprotection step involving the cleavage of the acetyl groups by
All commercially available products were purchased from
Aldrich (Saint-Quentin Fallavier, France) and used as received.

3228
M. Kajjout et al. / Tetrahedron 68 (2012) 3225e3230
Deuterated solvents (99.9% or better) were purchased from Euriso-
Top (Saint-Aubin, France). Tetrahydrofuran (THF) was distilled over
sodium benzophenone ketyl under argon before use. For flash
chromatography, Merck silica-gel 60 (230e400 mesh ASTM) was
used. The melting points were measured on an Electrothermal
(Dubuque, Iowa USA) 9100 apparatus and were not corrected. NMR
spectra were recorded on a Bruker (Wissembourg, France) AM 300
spectrometer (300, 282 and 75 MHz, for 1H, 19F and 13C, re-
spectively) using CDCl3 or CD3OD as solvents and TMS as internal
standard; chemical shifts and J values are given in parts per million
and hertz, respectively. Fast atom bombardment (FAB) mass spectra
were measured on a JEOL Mass Station 700 spectrometer at the
4.3.1. 2-Fluoro-3-phenyl-2-propenethioic
acid,
S-ethyl
ester
(6a). Mp 40e41 ꢁC. 19F NMR (CDCl3):
d
¼ꢀ125.1 (Z, d, 3JHF¼36.9 Hz,
3
1F), ꢀ116.7 (E, d, JHF¼24.3 Hz, 1F). 1H NMR (CDCl3):
d¼1.32 (t,
3JHH¼7.3 Hz, 3H), 2.85 (q, 3JHH¼7.3 Hz, 2H), 6.69 (d, E, 3JHF¼24.3 Hz,
0.9H), 6.87 (d, Z, 3JHF¼36.9 Hz, 0.1H), 7.38 (dd, 3JHH¼7.3 Hz, 1H), 7.42
(dd, 3JHH¼7.3 Hz, 7.4 Hz, 2H), 7.64 (d, 3JHH¼7.4 Hz, 2H). HRMS: calcd
for C11H12OFS [MþH]þ 211.0587; found 211.0592.
4.3.2. 2-Fluoro-3-(4-fluorophenyl)-2-propenethioic acid S-ethyl ester
(6b). Mp 43e45 ꢁC. 19F NMR (CDCl3):
d
¼ꢀ126.5 (dd, 3JHF¼36.4 Hz,
5JHF¼1.4 Hz, 1F), ꢀ109.4 (m, 1F). 1H NMR (CDCl3):
d¼1.33 (t,
3
3
3JHH¼7.4 Hz, 3H), 3.02 (q, JHH¼7.4 Hz, 2H), 6.77 (d, JHF¼36.4 Hz,
Ecole Normale Superieure (Paris, France).
1H), 7.09 (dd, 3JHH¼8.6 Hz, 3JHF¼8.6 Hz, 2H), 7.64 (dd, 3JHH¼8.2 Hz,
ꢀ
ꢀ
3JHF¼5.6 Hz, 2H). 13C NMR (CDCl3):
¼14.4, 22.9, 111.9, 116.1, 127.1,
d
132.7, 151.9, 163.3 (d, 1JCF¼269.3 Hz), 186.5 (d, 2JCF¼37.6 Hz). HRMS:
4.2. Synthesis of 2-(diethoxyphosphinyl)-2-fluoro-
ethanethioic acid, S-ethyl ester (4)
calcd for C11H11OF2S [MþH]þ 229.0493; found 229.0494.
4.3.3. 2-Fluoro-3-(4-nitrophenyl)-2-propenethioic acid, S-ethyl ester
4.2.1. 2-(Diethoxyphosphinyl)-2-fluoro-acetic acid (2). To a solution
of sodium hydroxide (4 mmol) in water (5 mL) and ethanol was
added a solution of 2-(diethoxyphosphinyl)-2-fluoro-acetic acid,
ethyl ester (4.4 mmol) in ethanol (10 mL). The reaction mixture was
stirred for 10 h at room temperature, and acidified to pH¼1 with 2%
HCl. The organic layer was extracted with ether, dried over MgSO4
(6c). Mp 45e46 ꢁC. 19F NMR (CDCl3):
d
¼ꢀ126.1 (d, Z, 3JHF¼35.3 Hz,
3
1F), ꢀ118.5 (d, E, JHF¼21.8 Hz, 1F). 1H NMR (CDCl3):
d¼1.27 (t, E,
3JHH¼7.3 Hz, 1.8H), 1.33 (t, Z, JHH¼7.3 Hz, 1.2H), 2.94 (q, E,
3
3JHH¼7.4 Hz, 1.2H), 3.04 (q, Z, JHH¼7.4 Hz, 0.8H), 6.66 (d, E,
3
3JHF¼21.8 Hz, 0.6H), 6.84 (d, Z, JHF¼35.3 Hz, 0.4H), 7.67 (d, E,
3
3JHH¼8.8 Hz, 1.2H), 7.78 (d, Z, JHH¼8.5 Hz, 0.8H), 7.96 (d, Z,
3
and the solvent was evaporated under reduced pressure to give the
3JHH¼8.4 Hz, 0.8H), 8.19 (d, E, JHH¼8.8 Hz, 1.2H). HRMS: calcd for
3
2
corresponding acid. 19F NMR (CDCl3):
d
¼ꢀ210.2 (dd, JHF¼46.9 Hz,
C11H11O3NFS [MþH]þ 256.0438; found 256.0441.
2JFP¼72.2 Hz, 1F). 1H NMR (CDCl3):
d
¼1.34 (t, 3JHH¼6.7 Hz, 6H), 4.27
(q, 3JHH¼7.1 Hz, 4H), 5.25 (dd, 2JHF¼46.9 Hz, 2JHP¼13.3 Hz, 1H), 10.15
4.3.4. 2-Fluoro-3-(3-bromophenyl)-2-propenethioic acid, S-ethyl es-
(OH, s, 1H). 13C NMR (CDCl3):
d
¼16.2 (2C), 64.9 (2C), 84.4 (d,
ter (6d). Mp 41e43 ꢁC. 19F NMR (CDCl3):
d
¼ꢀ123.1 (d, 3JHF¼36.2 Hz,
1JCF¼195.4 Hz), 165.7. HRMS: calcd for C6H13O5FP 215.0476; found
3
1F). 1H NMR (CDCl3):
d
¼1.34 (t, JHH¼7.6 Hz, 3H), 3.02 (q,
215.0479.
3
3
3JHH¼7.4 Hz, 2H), 6,74 (d, JHF¼36.2 Hz, 1H), 7.27 (dd, JHH¼7.9 Hz,
3JHH¼7.7 Hz, 1H), 7.51 (d, 3JHH¼7.9 Hz, 1H), 7.56 (d, 3JHH¼7.9 Hz, 1H),
4.2.2. 2-(Diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S-ethyl
ester (4). Thionyl chloride (4 mmol) was added to a solution of
compound 2 (2 mmol) in CH2Cl2 (5 mL) under argon in a flask fitted
with a reflux condenser. The solution was refluxed for 3 h, cooled to
room temperature and the solvent was evaporated. A solution of
ethanethiol (2 mmol) and triethylamine (2 mmol) in 20 mL of
CH2Cl2 was then added to the obtained acid chloride. The reaction
mixture was stirred for 4 h at room temperature. 20 mL of benzene
was added of the residue obtained after evaporation of the solvent
and the solution was filtered. The solvent was evaporated and the
product was isolated by flash column chromatography using
a mixture of ethyl acetate/petroleum ether 60/40 as eluent. 19F NMR
7.82 (s, 1H). 13C NMR (CDCl3):
d¼14.4, 23.1, 111.3, 123.0, 129.1, 130.3,
132.8, 132.8, 136.6, 151.3 (d, 1JCF¼273.6 Hz), 185.5 (d, 2JCF¼37.5 Hz).
HRMS: calcd for C11H11O79BrFS 288.9692 and for C11H11O81BrFS
290.9672; found 288.9694 and 290.9680.
4.3.5. 2-Fluoro-3-(2-methylphenyl)-2-propenethioic acid, S-ethyl
ester (6e). 19F NMR (CDCl3):
d
¼ꢀ117.8 (d, 3JHF¼21.2 Hz, 1F). 1H NMR
3
(CDCl3):
d
¼1.29 (t, JHH¼6.9 Hz, 3H), 2.32 (s, 3H), 2.94 (q,
3
3
3JHH¼6.7 Hz, 2H), 6,71 (d, JHF¼21.2 Hz, 1H), 7.24 (d, JHH¼7.1 Hz,
3
3
3
1H), 7.27 (dd, JHH¼7.4, JHH¼7.5 Hz, 1H), 7.35 (d, JHH¼7.4 Hz, 1H),
7.39 (dd, 3JHH¼7.1, 3JHH¼7.5 Hz, 1H). 13C NMR (CDCl3):
¼14.3, 20.1,
d
22.7, 116.5, 125.5, 128.9, 129.6, 129.8, 129.9, 136.6, 151.3 (d,
2
2
(CDCl3):
d
¼ꢀ207.3 (dd, JHF¼46.7 Hz, JFP¼71.5 Hz, 1F). 1H NMR
1JCF¼257.5 Hz), 185.5 (d, JCF¼41.1 Hz). HRMS: calcd for C12H14OFS
2
3
3
(CDCl3):
d
¼1.23 (t, JHH¼7.3 Hz, 3H), 1.30 (t, JHH¼6.5 Hz, 6H), 2.92
225.0749; found 225.0751.
3
3
(q, JHH¼7.2 Hz, 2H), 4.18 (q, JHH¼6.7 Hz, 4H), 5.16 (dd,
2JHF¼46.7 Hz, 2JHP¼11.9 Hz, 1H). 13C NMR (CDCl3):
d
¼14.2, 16.2 (2C),
4.3.6. 2,3,4,6-Tetra-O-acetyl-1-[4-((2Z)-2-fluoro-3-hydroxyprop-1-
enyl, 2-propenethioic acid, S-ethyl)-2-methoxyphenyl]-b-D-glucopyr-
1
2
22.8, 64.3 (2C), 91.0 (d, JCF¼158.0 Hz), 193.7 (d, JCF¼25.0 Hz).
HRMS: calcd for C8H17O4FPS [MþH]þ 259.0563; found 259.0569.
anoside (6f). Mp 126e128 ꢁC. 19F NMR (CDCl3):
d
¼ꢀ126.4 (Z, d,
3JHF¼36.6 Hz, 1F), ꢀ116.95 (E, d, 3JHF¼25.1 Hz, 1F). 1H NMR (CDCl3):
4.3. General procedure for the preparation of
a
-
d
¼1.25 (t, E, 3JHH¼7.3 Hz, 2.4H), 1.29 (t, Z, 3JHH¼7.3 Hz, 0.6H), 2.04 (s,
fluorocinnamic thioesters
3H), 2.08 (s, 6H), 2.10 (s, 3H), 2.96 (q, E, 3JHH¼7.3 Hz,1.6H), 3.01 (q, Z,
3JHH¼7.3 Hz, 0.4H), 3.78e3.83 (m, 1H), 3.85 (s, 3H), 4.12 (dd,
2JHH¼14.3 Hz, 3JHH¼7.1 Hz, 1H), 4.29 (dd, 2JHH¼12.3 Hz, 3JHH¼4.9 Hz,
To a stirred solution of 2-(diethoxyphosphinyl)-2-fluoro-etha-
nethioic acid, S-ethyl ester (1.50 mmol) in anhydrous THF (10 mL),
n-butyllithium (1.70 mmol) were added slowly at ꢀ70 ꢁC. The so-
lution was stirred at ꢀ70 ꢁC for 1 h. A solution of corresponding
aldehydes (1.20 mmol) in anhydrous THF (5 mL) was added drop-
wise, and the reaction mixture was stirred at ꢀ70 ꢁC for 4 h and at
room temperature for 18 h. The reaction was quenched with water
(50 mL), and the mixture was extracted with CH2Cl2 (3ꢂ50 mL). The
combined organic extracts were dried over MgSO4 and concen-
trated under reduced pressure. The residue was purified by flash
column chromatography using a mixture of ethyl acetate/petro-
leum ether to give the product.
3
1H), 5.01e5.2 (m, 1H), 5.25e5.32 (m, 3H), 6,61 (d, E, JHF¼25.1 Hz,
0.8H), 6.77 (d, Z, 3JHF¼36.6 Hz, 0.2H), 7.09 (d, 3JHH¼8.4 Hz, 1H), 7.14
3
(d, JHH¼8.4 Hz, 1H), 7.44 (s, 1H). HRMS: calcd for C26H35O12NFS
[MþNH4]þ 604.1859; found 604.1862.
4.4. General procedures for the reduction of a-
fluorocinnamic acid thioesters
NaBH4 (2.5 mmol) was added to a solution of thioesters
(0.5 mmol) in EtOH (10 mL). The solution was stirred at room
temperature for 24 h, after solvent evaporation, the residue was

M. Kajjout et al. / Tetrahedron 68 (2012) 3225e3230
3229
extracted with CH2Cl2 (2ꢂ50 mL). The organic layer was dried over
MgSO4 and the solvent was evaporated. The product was isolated
by flash column chromatography using dichloromethane as eluent.
sodium methoxide, prepared from 10 mg of sodium metal in
methanol (10 mL) was added. When the deprotection was com-
pleted, the solution was neutralized by adding 2.0 g of an ion-ex-
change resin (Hþ form). The agitation was maintained for 30 min,
and then the resin was filtered. The methanol was eliminated by
vacuum evaporation, at room temperature. The product was iso-
lated by chromatography on a C18 cartridge (LC-SPE) using a mix-
ture of MeOH/H2O 30/70 as eluent. Mp 141e142 ꢁC. 19F NMR
4.4.1. (2Z)-2-Fluoro-3-phenyl-2-propen-1-ol (7a). 19F NMR (CDCl3):
d
¼ꢀ110.9 (dt, 3JHF¼38.9 Hz, 3JHF¼14.8 Hz). 1H NMR (CDCl3):
d
¼4.56 (d,
3
3JHF¼14.8 Hz, 2H), 5.55 (d, JHF¼38.9 Hz, 1H), 7.25 (m, 1H), 7.31 (d,
3JHH¼8.4Hz,2H), 7.50(d, 3JHH¼8.4 Hz, 2H).13CNMR(CDCl3):
¼61.2 (d,
d
2JCF¼28.8 Hz),102.3,128.2,128.9,130.2,132.0,157.9 (d, 1JCF¼265.9 Hz).
HRMS: calcd for C9H10OF [MþH]þ 153.0710; found 153.0707.
(CD3OD):
(CD3OD):
d
¼ꢀ113.1 (dt, JHF¼38.9 Hz, JHF¼15.4 Hz, 1F). 1H NMR
3
3
d¼3.25e3.45 (m, 4H), 3.62 (m, 1H), 3.71 (m, 1H), 3.83 (s,
3
3
3H), 4.20 (d, JHF¼15.4 Hz, 2H), 4.82 (d, JHH¼7.0 Hz, 1H), 5.80 (d,
3
3
4.4.2. (2Z)-2-Fluoro-3-(4-fluororophenyl)-2-propen-1-ol
(7b). 19F
¼ꢀ114.8 (dt, JHF¼37.9 Hz, JHF¼14.3 Hz, 1F), 113.9
3JHF¼38.9 Hz, 1H), 7.04 (d, JHH¼8.3 Hz, 1H), 7.13 (d, JHH¼8.1 Hz,
3
3
2
NMR (CDCl3):
d
1H), 7.18 (s, 1H). 13C NMR (CD3OD):
d¼56.7, 61.8 (d, JCF¼32.2 Hz),
3
(m, 1F). 1H NMR (CDCl3):
d
¼4.26 (d, JHF¼14.5 Hz, 2H), 5.76 (d,
62.5, 71.3, 75.0, 77.8, 78.1, 102.6, 107.7, 114.0, 117.7, 123.2, 129.6,
147.3, 150.5, 159.9 (d, 1JCF¼265.9 Hz). HRMS: calcd for C16H25O8NF
[MþNH4]þ 378.1559; found 378.1555.
3JHF¼37.9 Hz, 1H), 7.01 (dd, 3JHF¼8.7 Hz, 3JHH¼8.7 Hz, 2H), 7.47 (dd,
4
3JHH¼8.7 Hz, JHF¼5.4 Hz, 2H). 13C NMR (CDCl3):
d¼61.9 (d,
2JCF¼32.6 Hz), 106.5 (d, JCF¼6.8 Hz), 115.6 (d, JCF¼21.5 Hz), 128.8,
2
2
130.3 (dd, JCF¼8.4 Hz, JCF¼8.4 Hz), 157.5 (d, 1JCF¼263.8 Hz), 162.4
3
4
Acknowledgements
(d, JCF¼247.5 Hz). HRMS: calcd for C9H9OF2 [MþH]þ 171.0616;
1
found 171.0614.
The NMR and Mass Spectrometry facilities used in this study
ꢀ
were funded by the European Community (FEDER), the Region
4.4.3. (2Z)-2-Fluoro-3-(4-nitrophenyl)-2-propen-1-ol (7c). 19F NMR
ꢀ
Nord-Pas de Calais (France), the CNRS, and the Universite de Lille 1,
Sciences et Technologies. SE thanks the Universite Cadi Ayyad,
Faculte des Sciences et Techniques Gueliz, Marrakech, Morocco for
a sabbatical leave and the Region Nord-Pas de Calais (France) for
a position as an invited professor. The authors thank Dr. Maria van
Agthoven for her help with editing this manuscript.
(CDCl3):
d
¼ꢀ107.5 (dt, 3JHF¼37.9 Hz, 3JHF¼11.2 Hz). 1H NMR (CDCl3):
ꢀ
3
3
ꢀ
ꢀ
d
¼4.35 (d, JHF¼11.2 Hz, 2H), 5.86 (d, JHF¼37.9 Hz, 1H), 7.62 (d,
3JHH¼8.8 Hz, 2H), 8.19 (d, 3JHH¼8.8 Hz). 13C NMR (CDCl3):
¼61.3 (d,
d
ꢀ
2JCF¼33.9 Hz), 105.1, 123.8, 129.1, 139.4, 146.5, 161.2 (d,
1JCF¼272.7 Hz). HRMS: calcd for C9H9O3NF [MþH]þ 198.0561;
found 198.0560.
Supplementary data
4.4.4. (2Z)-2-Fluoro-3-(3-bromophenyl)-2-propen-1-ol
(7d). 19F
NMR (CDCl3):
(CDCl3):
d
¼ꢀ111.2 (dt, 3JHF¼38.2 Hz, 3JHF¼14.0 Hz,1F). 1H NMR
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2012.02.039. These data in-
clude MOL files and InChIKeys of the most important compounds
described in this article.
3
3
d
¼4.30 (d, JHF¼14.0 Hz, 2H), 5.73 (d, JHF¼38.2 Hz, 1H),
7.20 (dd, 3JHH¼7.9 Hz; 7.43 Hz, 1H), 7.38 (d, 3JHH¼7.5 Hz, 1H), 7.42 (d,
3JHH¼7.9 Hz, 1H), 7.68 (s, 1H). 13C NMR (CDCl3):
d
¼61.6 (d,
2JCF¼33.0 Hz), 106.1, 122.5, 127.2, 129.9, 130.5, 131.5, 134.6, 159.1 (d,
1JCF¼268.7 Hz). HRMS: calcd for C9H9O79BrF 230.9815 and for
C9H9O81BrF [MþH]þ 232.9795; found 230.9820 and 232.9802.
References and notes
1. (a) Boehm, H.-J.; Banner, D.; Bendels, S.; Kansy, M.; Kuhn, B.; Mueller, K.; Obst-
Sander, U.; Stahl, M. ChemBioChem 2004, 5, 637e643; (b) Jeschke, P. Chem-
BioChem 2004, 5, 570e589; (c) Ojima, I. ChemBioChem 2004, 5, 628e635.
2. Kirk, K. L. J. Fluorine Chem. 2006, 127, 1013e1029.
3. (a) Yanai, H.; Taguchi, T. Eur. J. Org. Chem. 2011, 2011, 5939e5954; (b) Landelle,
G.; Bergeron, M.; Turcotte-Savard, M.-O.; Paquin, J.-F. Chem. Soc. Rev. 2011, 40,
2867e2908.
4. (a) Burkhart, J. P.; Weintraub, P. M.; Gates, C. A.; Resvick, R. J.; Vaz, R. J.; Frie-
drich, D.; Angelastro, M. R.; Bey, P.; Peet, N. P. Bioorg. Med. Chem. 2002, 10,
929e934; (b) Michel, D.; Schlosser, M. Tetrahedron 2000, 56, 4253e4260; (c)
Poulter, C. D.; King, C. H. R. J. Am. Chem. Soc. 1982, 104, 1422e1424; (d) Wei, H.-
X.; Schlosser, M. Eur. J. Org. Chem. 1998, 2603e2607.
5. (a) Luo, F.; Wang, P.; Gong, Y. Tetrahedron Lett. 2010, 51, 1693e1695; (b) Pierry,
C.; Zoute, L.; Jubault, P.; Pfund, E.; Lequeux, T.; Cahard, D.; Couve-Bonnaire, S.;
Pannecoucke, X. Tetrahedron Lett. 2009, 50, 264e266; (c) Engman, M.; Diesen, J.
S.; Paptchikhine, A.; Andersson, P. G. J. Am. Chem. Soc. 2007, 129, 4536e4537.
6. Pierry, C.; Cahard, D.; Couve-Bonnaire, S.; Pannecoucke, X. Org. Biomol. Chem.
2011, 9, 2378e2386.
4.4.5. (2Z)-2-Fluoro-3-(2-methylphenyl)-2-propen-1-ol
(7e). 19F
3
3
NMR (CDCl3):
NMR (CDCl3):
d
¼ꢀ115.6 (dt, JHF¼37.9 Hz, JHF¼20.3 Hz, 1F). 1H
3
d
¼2.31 (s, 3H), 4.91 (d, JHF¼20.3 Hz, 2H), 5.92 (d,
3JHF¼37.9 Hz, 1H), 7.14 (d, JHH¼7.1 Hz, 1H), 7.17 (dd, JHH¼7.4 Hz;
3
3
7.5 Hz, 1H), 7.24 (d, 3JHH¼7.4 Hz, 1H), 7.39 (dd, 3JHH¼7.1 Hz; 7.5 Hz,
1H). 13C NMR (CDCl3):
d
¼18.1, 61.3 (d, JCF¼31.8 Hz), 105.2, 111.7,
2
114.6, 125.7, 128.2, 132.0, 135.1, 157.7 (d, 1JCF¼265.6 Hz) ppm. HRMS:
calcd for C10H12OF [MþH]þ 167.0872; found 167.0875.
4.4.6. 2,3,4,6-Tetra-O-acetyl-1-[4-((2Z)-2-fluoro-3-hydroxyprop-1-
enyl)-2-methoxyphenyl]-b-D
-glucopyranoside (7f). Mp 133e134 ꢁC.
19F NMR (CDCl3):
NMR (CDCl3):
d
¼ꢀ114.67 (dt, 3JHF¼38.5 Hz, 3JHF¼14.3 Hz, 1F). 1H
d
¼2.00 (s, 6H), 2.04 (s, 6H), 3.63e3.70 (m, 1H), 3.80
7. Daubresse, N.; Chupeau, Y.; Francesch, C.; Lapierre, C.; Pollet, B.; Rolando, C.
Chem. Commun. 1997, 1489e1490.
2 3
(s, 3H), 4.15 (dd, JHH¼14.3 Hz, JHH¼7.1 Hz, 1H), 4.20 (dd,
2JHH¼12.3 Hz, JHH¼4.9 Hz, 1H), 4.22 (d, JHF¼14.3 Hz, 2H),
3
3
8. (a) Wengenmayer, H.; Ebel, J.; Grisebach, H. Eur. J. Biochem. 1976, 65, 529e536;
(b) Humphreys, J. M.; Chapple, C. Curr. Opin. Plant Biol. 2002, 5, 224e229.
9. (a) Barron, E. J.; Mooney, L. A. Anal. Chem. 1968, 40, 1742e1744; (b) Nagao, Y.;
Kawabata, K.; Fujita, E. J. Chem. Soc., Chem. Commun. 1978, 330; (c) Liu, H. J.;
Bukownik, R. R.; Pednekar, P. R. Synth. Commun. 1981, 11, 599e603; (d) Liu, H. J.;
Luo, W. Can. J. Chem. 1992, 70, 128e134.
10. Day, A.; Neutelings, G.; Nolin, F.; Grec, S.; Habrant, A.; Cronier, D.; Maher, B.;
Rolando, C.; David, H.; Chabbert, B.; Hawkins, S. Plant Physiol. Biochem. 2009, 47,
9e19.
11. (a) Coutrot, P.; Charbonnier, C.; Grison, C. Synthesis 1991, 23e26; (b) Liu, H. J.;
Rose, P. A.; Sasaki, D. J. Can. J. Chem. 1991, 69, 934e936; (c) Schaumann, E.;
Mergardt, B.; Fittkau, S. Synthesis 1990, 47e51.
12. (a) Keck, G. E.; Boden, E. P.; Mabury, S. A. J. Org. Chem. 1985, 50, 709e710; (b)
Lucast, D. H.; Wemple, J. Tetrahedron Lett. 1977, 1103e1106; (c) van Zijl, A. W.;
Minnaard, A. J.; Feringa, B. L. J. Org. Chem. 2008, 73, 5651e5653; (d) den Hartog,
T.; van Dijken, D. J.; Minnaard, A. J.; Feringa, B. L. Tetrahedron: Asymmetry 2010,
21, 1574e1584.
3
5.07e5.17 (m, 2H), 5.24e5.29 (m, 2H), 5.65 (d, JHF¼38.5 Hz, 1H),
6.92 (d, 3JHH¼7.8 Hz, 1H), 7.02 (d, 3JHH¼8.0 Hz, 1H), 7.08 (s, 1H). 13
C
2
NMR (CDCl3):
d
¼20.6, 56.0, 61.6 (d, JCF¼32.7 Hz), 61.9, 68.4, 71.2,
72.0, 72.7, 100.6, 106.6, 112.9, 119.7, 121.5, 128.6, 145.3, 150.3, 158.1
(d, 1JCF¼266.2 Hz), 169.4, 170.3, 170.7. HRMS: calcd for C24H33O12NF
[MþNH4]þ 546.1981; found 546.1990.
4.5. 1-[4-((2Z)-2-fluoro-3-hydroxyprop-1-enyl)-2-
methoxyphenyl]-b-D-glucopyranoside, (Z)-befluoroconiferin (8)
2,3,4,6-tetra-O-acetyl-1-[4-((2Z)-2-fluoro-3-hydroxyprop-1-
enyl)-2-methoxyphenyl]- -glucopyranoside (0.5 mmol) 7f was
dissolved in 40 mL of a mixture of MeOH/THF (50:50). A solution of
b-D
13. Pirrung, M. C.; Rowley, E. G.; Holmes, C. P. J. Org. Chem. 1993, 58, 5683e5689.

3230
M. Kajjout et al. / Tetrahedron 68 (2012) 3225e3230
14. (a) Inagaki, H.; Takeda, T.; Miyauchi, R. N.; Kawakami, K.; Takahashi, H.; Take-
mura, M. Heterocycles 2004, 63, 699e706; (b) Zhao, S.; He, Y.-h.; Wu, D.; Guan,
Z. J. Fluorine Chem. 2010, 131, 597e605.
15. (a) Coutrot, P.; Ghribi, A. Synthesis 1986, 661e664; (b) Teichert, A.; Jantos, K.;
Harms, K.; Studer, A. Org. Lett. 2004, 6, 3477e3480.
21. (a) Beak, P.; Becker, P. D. J. Org. Chem. 1982, 47, 3855e3861; (b) Tsunoda, T.;
Nagaku, M.; Nagino, C.; Kawamura, Y.; Ozaki, F.; Hioki, H.; Ito, S. Tetrahedron
Lett. 1995, 36, 2531e2534; (c) Back, T. G.; Baron, D. L.; Yang, K. J. Org. Chem.
1993, 58, 2407e2413; (d) Kotsuki, H.; Yoshimura, N.; Ushio, Y.; Ohtsuka, T.;
Ochi, M. Chem. Lett. 1986, 1003e1004.
16. (a) Etemad-Moghadam, G.; Seyden-Penne, J. Bull. Soc. Chim. Fr. 1985, 448e454;
(b) Sano, S.; Teranishi, R.; Nagao, Y. Tetrahedron Lett. 2002, 43, 9183e9186.
17. Thenappan, A.; Burton, D. J. J. Org. Chem. 1990, 55, 4639e4642.
18. Appel, R.; Loos, R.; Mayr, H. J. Am. Chem. Soc. 2009, 131, 704e714.
19. Romanenko, V. D.; Kukhar, V. P. Chem. Rev. 2006, 106, 3868e3935.
20. (a) Fukuyama, T.; Lin, S. C.; Li, L. J. Am. Chem. Soc. 1990, 112, 7050e7051; (b)
Fukuyama, T.; Tokuyama, H. Aldrichimica Acta 2004, 37, 87e96; (c) Tokuyama,
H.; Yokoshima, S.; Lin, S.-C.; Li, L.; Fukuyama, T. Synthesis 2002, 1121e1123; (d)
Kimura, M.; Seki, M. Tetrahedron Lett. 2004, 45, 3219e3223; (e) van Zijl, A. W.;
Szymanski, W.; Lopez, F.; Minnaard, A. J.; Feringa, B. L. J. Org. Chem. 2008, 73,
6994e7002; (f) Evans, D. A.; Connell, B. T. J. Am. Chem. Soc. 2003, 125,
10899e10905.
22. (a) Pawson, B. A.; Chan, K. K.; DeNoble, J.; Han, R. J.; Piermattie, V.; Specian, A.
C.; Srisethnil, S.; Trown, P. W.; Bohoslawec, O.; Machlin, L. J.; Gabriel, E. J. Med.
Chem. 1979, 22, 1059e1067; (b) Jin, Y.; Williams, D. C.; Croteau, R.; Coates, R. M.
J. Am. Chem. Soc. 2005, 127, 7834e7842.
23. Ducry, L.; Roberge, D. M. Org. Process Res. Dev. 2008, 12, 163e167.
24. Ranu, B. C.; Mandal, T. Aust. J. Chem. 2007, 60, 223e227.
25. Daubresse, N.; Francesch, C.; Rolando, C. Tetrahedron 1998, 54, 10761e10770.
26. Daubresse, N.; Francesch, C.; Mhamdi, F.; Rolando, C. Synthesis 1998, 157e161.
27. Zemmouri, R.; Kajjout, M.; Castanet, Y.; Eddarir, S.; Rolando, C. J. Org. Chem.
2011, 76, 7691e7698.
28. Rolando, C.; Daubresse, N.; Pollet, B.; Jouanin, L.; Lapierre, C. C. R. Biol. 2004,
327, 799e807.