Efficient access to fluorinated homoallylic alcohols through an indium promoted fluoroallylation reaction

Article abstract of DOI:10.1016/j.tet.2014.03.067

Herein, an efficient access to fluorinated homoallylic alcohol is reported. The fluorinated alcohols were obtained in good to excellent yield using indium and halo-fluorinated allylic derivatives. The developed methodology using γ-substituted halo-fluorin

Full text of DOI:10.1016/j.tet.2014.03.067

Tetrahedron 70 (2014) 3123e3133
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient access to fluorinated homoallylic alcohols through an
indium promoted fluoroallylation reaction
*
ꢀ
Gerald Lemonnier, Nathalie Van Hijfte, Muriel Sebban, Thomas Poisson ,
*
Samuel Couve-Bonnaire, Xavier Pannecoucke
ꢁ
Normandie Univ, COBRA, UMR 6014 et FR 3038, Univ. Rouen, INSA Rouen, CNRS, 1 rue Tesniere, 76821 Mont Saint-Aignan Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Herein, an efficient access to fluorinated homoallylic alcohol is reported. The fluorinated alcohols were
obtained in good to excellent yield using indium and halo-fluorinated allylic derivatives. The developed
Received 11 February 2014
Received in revised form 15 March 2014
Accepted 19 March 2014
methodology using
substituted fluorinated homoallylic alcohol in good yields and good diastereoselectivities up to 86:14.
Ó 2014 Elsevier Ltd. All rights reserved.
g-substituted halo-fluorinated allylic derivatives gave the corresponding a-
Available online 25 March 2014
Keywords:
Fluorine
Fluoroolefins
Allylation reaction
Indium
1. Introduction
Fluorine atom has the impressive ability to affect the physical
and chemical properties of organic molecules.1 As a result, this
intriguing atom is present in around 20% of pharmaceuticals and
40% of agrochemicals.2 Therefore, it is not surprising that a lot of
attention has been recently devoted to the synthesis of fluorinated
molecules.3 Among all the fluorinated molecules, fluoroolefins are
of great interest4 and can be used for instance as peptidomimetics5
or in material science6 in order to modify the physical properties.
Moreover, fluoroolefins are present in several bioactive com-
pounds, such as anti-diabetics7 or anti-HIV8 agents (Fig. 1).
Besides homoallylic alcohols are considered as a key building
block in organic synthesis allowing a huge number of post-
functionalizations.9 Thus, as part of our research program devoted
to the synthesis of relevant fluorinated building blocks10 we sought
to design a new and straightforward access to secondary and ter-
tiary fluorinated homoallylic alcohols. Although, pioneering work
from Allmendinger11 showed the versatility of such compounds,
quite surprisingly the reports dealing with the direct access to these
scaffolds are quite scarce in the literature. So far, the synthesis of
such compounds remains challenging and to our knowledge, either
Fig. 1. Examples of relevant fluoroolefins.
an Ir-catalyzed dehydrogenative CeC forming bond12 or a syn-se-
lective HosomieSakurai13 reaction have been successfully reported
to access to these compounds (Fig. 2a).
Noteworthy, both methodologies required either the use of an
expensive noble metal (Ir) or a painstaking synthesis of the fluo-
rinated starting materials. To tackle these major drawbacks, we
focused our approach on the use of readily available fluorinated
starting material and indium metal as promoter of the allylation
* Corresponding authors. Tel.: þ33 2 35 52 24 11; fax: þ33 2 35 52 29 59 (T.P.);
tel.: þ33 2 35 52 24 20; fax: þ33 2 35 52 29 59 (X.P.); e-mail addresses: thomas.
poisson@insa-rouen.fr (T. Poisson), xavier.pannecoucke@insa-rouen.fr (X.
Pannecoucke).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.03.067

3124
G. Lemonnier et al. / Tetrahedron 70 (2014) 3123e3133
(entry 5). Finally, the change of water to brine16 afforded a complete
conversion of the starting material and the product was isolated in
nearly quantitative yield (entry 6).
With these established conditions in hand, we moved on the
extension of the scope of the reaction (Table 2). First, aromatic al-
dehydes were engaged under our reaction conditions. Pleasingly,
the reaction proceeded smoothly in the presence of electron-
withdrawing or electron-donating groups onto aromatic back-
bones (entries 1e4). Ester derivative 1b as well as unprotected
phenol 1e are suitable and the desired products 2b and 2e were
obtained in 88% and 73% yield, respectively (entries 2 and 5).
a-
Substituted- -unsaturated aldehydes are compatibles and the
a,b
addition product 2f was isolated in 87% yield. Next, heteroaromatic
compounds were screened and gratefully thiophene adduct 2g and
pyridine derivative 2h were isolated in good yields (entries 7 and
8). The valuable pyrimidine derivative 1i bearing a free amine
group reacted smoothly, thus affording the product 2i in 99% yield
(entry 9). Ferrocene derivative 1j gave the addition product 2j in
excellent yield (entry 10). Then, we turn our attention to aliphatic
aldehydes, hydrocinnamaldehyde 1k afforded the corresponding
adduct 2k in 99% yield (entry 11), while nonanal 1l and citronellal
1m gave lower yield, 60 and 57% yield, respectively, probably due to
their high volatility (entries 12e13). When reactions were carried
out with citronellal 1m and aldehyde 1n no significant diaster-
eoselectivities were measured (entries 13 and 14). Similarly,
(ꢀ)-Menthyl glyoxalate hydrate 1o gave the addition product 2o in
92% yield as a 1:1 mixture of diastereomers (entry 15). To our de-
light, this methodology was applied to complexes fluorinated cy-
clopropanes 1p and 1q and the corresponding addition products 2p
and 2q were obtained in pretty good yield and good to excellent
diastereoisomeric ratio (entry 16 and 17).17 Then, ketones were
investigated. Unfortunately, using our standard conditions ketones
1r reacted poorly and 2r was obtained in 13% yield along with the
recovery of the unreacted starting material (entry 18). Using acti-
vated ketone 1s as starting material, a solvent survey shown that an
increase of the temperature to 60 ꢁC using THF as a solvent allowed
the formation of the addition product 2s in 99% yield (entry 19).
With these new conditions, ketones 1t gave the desired adduct in
57% yield (entries 20). Unfortunately, despite several attempts we
have not been able to improve the reaction using 1r as a substrate.
Having established a practical and efficient access to fluorinated
homoallylic alcohol, we decided to go further and to design an
access to more complex fluorinated structures using elaborated
Fig. 2. Access to fluorinated homoallylic alcohols.
reaction (Fig. 2b).14 Indium metal gives numerous advantages
compared to other metal, (1) its use does not require any prior-to-
use activation of the metal, (2) indium mediated addition can be
used under Barbier conditions, thus avoiding any initial formation
of the organometallic species, (3) indium metal and organo-indium
derivatives have a broad functional group tolerance and (4) finally
indium and associated reagents present a very low toxicity. Thus,
we report herein a full account15 of our investigations to develop an
easy access to homoallylic alcohols by means of an indium pro-
moted allylation reaction on carbonyl compounds.
2. Results and discussion
Initially, we focused our attention to the allylation reaction of
aldehydes using indium metal and 3-chloro-2-fluoroprop-1-ene as
a commercially available fluorinated building block. Our initial at-
tempt using 1.2 equiv of indium metal and 1.1 equiv of 3-chloro-2-
fluoroprop-1-ene afforded the desired homoallylic alcohol in 72%
yield using water as a solvent (Table 1, entry 1). The use of 2 equiv of
indium afforded a slight improve of the reaction yield to 76% (entry
2), while the use of 1.5 equiv of indium and 1.5 equiv of 3-chloro-2-
fluoroprop-1-ene gave a significant enhancement of the reaction
yield to 90% yield. The use of 2 equiv of indium instead of 1.5 equiv
of fluorinated substrate did not provide further improvements
(entry 4). Finally, the use of 2 equiv of indium and 3-chloro-2-
fluoroprop-1-ene gave the desired product in 91% isolated yield
halo-fluorinated allylic compounds. The
fluorinated allylic derivatives 5 were readily synthesized starting
from the corresponding
-fluoroacrylates 3.18 Reduction of the es-
g-substituted bromo-
a
ter function mediated by LiBH4 gave the allylic alcohols 4 in
pretty decent yields. Then, a bromination reaction of the allylic
alcohol 4 using PBr3 afforded the corresponding
g-substituted
bromofluorinated allylic derivatives 5 in pretty good overall yield
(Table 3).
Table 1
Optimization of the reaction conditions
With these substrates in hand and in order to settle the opti-
mized reaction conditions we carried out the addition reaction
using the bromo derivatives 5a with 4-chlorobenzaldehyde 1a
under various conditions (Table 4).
First, we checked the influence of the metal on the stereo-
chemical outcome of the reaction and we observed that indium was
the best metal to promote the reaction. Indeed, Mn gave no reaction
(Table 4, entry 1) while inactivated zinc and tin led to low yield and
low diastereoselectivity (entries 2 and 3). We were pleased to ob-
Entry
Solvent
x equiv
y equiv
Yield %a
1
2
3
4
5
6
H2O
H2O
H2O
H2O
H2O
Brine
1.2
2
1.5
2
2
2
1.1
1.1
1.5
1.5
2
72
76
90
89
served that indium afforded exclusively the g-adduct in quantita-
tive yield with a 80:20 anti:syn diastereoisomeric ratio (entry 4).19
Next, a solvent survey was performed: THF and DMF gave lower
yield and lower diastereoselectivity (entries 5 and 6) while brine
affords similar results (entry 7). Interestingly, the reaction pro-
ceeded smoothly in EtOH as a solvent. Moreover, we observed
98 (91)b
100 (99)b
2
a
Determined by 19F NMR and 1H NMR of the crude product using an internal
standard.
b
Isolated yield.

G. Lemonnier et al. / Tetrahedron 70 (2014) 3123e3133
Table 2 (continued )
3125
Table 2
Scope of the reactiona
Entry
Starting material
Product
Yield %b
57
20f
1t
a
Conditions: 1 (1 equiv), 3-chloro-2-fluoropropene (2 equiv), In(0) (2 equiv),
Entry
1
Starting material
Product
Yield %b
99
brine (0.3 M), rt, 16 h.
b
Isolated yield.
c
72 h reaction time.
d
Reaction performed at 40 ꢁC for 72 h.
1a
1b
e
Reaction performed at 60 ꢁC for 24 h.
f
Reaction performed at 60 ꢁC in THF for 24 h.
g
Diastereoisomeric ratio determined by 19F NMR on the crude reaction mixture.
2
88
Table 3
Preparation of g-substituted a-bromo fluorinated allylic derivatives 5
3
1c
66
99
4d
1d
5
1e
1f
73
87
Entry
R
4, %a
5, %a
Overall yield %
1
2
3
4
Ph
4a, 94
4b, 32
4c, 69
4d, 92
5a, 88
5b, 50
5c, 91
5d, 84
82
16
62
77
C6H5e(CH2)2
4-BreC6H4
4-OCH3eC6H4
6c
a
Isolated yield.
7
1g
1h
83
77
Table 4
Optimization of the reaction conditions
8c
9
1i
79
10
1j
99
99
Entry
Solvent
Metal
x equiv
y equiv
Yield %a ()b
1
2
3
4
5
6
7
8
H2O
H2O
H2O
H2O
Mn
Zn
Sn
In
In
In
In
In
In
In
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1
NR
33 (64:36)
48 (ND)
11d
1k
95 (80:20)
37 (58:42)
30 (ND)
THF
DMF
Brine
EtOH
EtOH
EtOH
12e
13e
14e
1l
60
95c (79:21)
95c (82:18)
90c (85:15)
100 (83:17)
57 (53:47)g
97 (50:50)g
9
1m
1n
10d
1.5
1.5
a
Determined by 19F NMR and 1H NMR of the crude product using an internal
standard.
b
c
anti:syn ratio determined by 19F NMR on the crude reaction mixture.
Isolated yield.
Reaction performed at rt for 24 h.
d
15
1o
92 (50:50)g
a cleaner crude reaction mixture than in aqueous media along with
a higher anti:syn ratio. The desired product 6a was obtained in al-
most quantitative yield with a 82:18 diastereoisomeric ratio (entry
8). A decrease of the amount of indium metal and 5a from 1.5 to
1 equiv gave a better diastereoisomeric ratio, 85:15 despite a slight
decrease of the reaction yield (entry 9). Finally, we conducted the
reaction at room temperature and after 24 h reaction time we have
16d
17d
18d
1p
1q
1r
63 (80:20)g
83 (100:0)g
13
been able to isolate the
a pleasant 83:17 diastereoisomeric ratio (entry 10).
Noteworthy, only the -adduct was observed in the crude re-
action mixture and a X-ray analysis of the major product revealed
that the process delivered the anti adduct as major di-
astereoisomer (Fig. 3).20 Noteworthy, this process represents the
g-adducts in nearly quantitative yield with
g
19f
1s
99
a

3126
G. Lemonnier et al. / Tetrahedron 70 (2014) 3123e3133
Table 5
first access to the anti-addition product, whereas Usuki and co-
workers12 approach provides predominantly the syn-adduct. Hav-
ing these conditions in hand we extended the scope of the reaction
to various aldehydes (Table 5).
Scope of the reactiona
These optimized conditions have been applied to a broad range
Entry
1
Starting material
5
Major product
Yield %b ()c
90 (85:15)
1a
1u
1v
1g
1w
1k
1x
1l
5a
2
3
4
5
6
7
8
5a
5a
5a
5a
5a
5a
5a
87 (81:19)
82 (80:20)
57 (86:14)
78 (60:40)
83 (64:36)
70 (63:37)
39 (64:36)
Fig. 3. Relative configuration of anti-6a by X-ray analysis.
of aldehydes. Reaction was first performed with the bromoallyl
derivative 5a. Electron rich aldehyde 1u afforded the corresponding
additions product 6b in 87% yield with a pleasant 81:19 di-
astereoisomeric ratio (entry 2). Piperonal gave the desired product
6c in 82% yield with a pretty similar diastereoisomeric ratio (80:20,
entry 3). Heteroaromatic aldehydes were compatible under our
reaction conditions and thiophene adduct 6d was isolated in 57%
yield and a 86:14 anti:syn ratio (entry 4). To our delight, (E)-cro-
tonaldehyde 1w reacted with 5a to give the addition product 6e in
good yield with a lower diastereoisomeric ratio (60:40, entry 5).
Then reaction was carried out with aliphatic aldehydes, hydro-
cinnamaldehyde 1k and pentanal 1x reacted with 5a to give the
addition product in pretty good yield and a decent anti:syn ratio,
64:36 and 63:37, respectively (entries 6 and 7). Surprisingly,
nonanal gave the corresponding addition product 6h in a modest
yield with 64:36 diastereoisomeric ratio (entry 8). Then, the ali-
phatic substituted bromo allylic derivative 5b was tested under our
reaction condition. para-Chlorobenzaldehyde reacted nicely with
5b to give the addition product 6i in 62% yield as an equal mixture
of anti and syn diastereoisomers (entry 9). (E)-Crotonaldehyde 1w
was engaged and afforded 6j in 70% yield with a reverse diaster-
eoselectivity (entry 10), while the aliphatic pentanal gave an equal
mixture of syn and anti diastereoisomers in 50% yield (entry 11).
Reaction was then carried out with 5c and aldehyde 1a giving the
addition product 6l in 62% yield with a 82:18 diastereoisomeric
ratio (entry 12). (E)-Crotonaldehyde 1x and pentanal gave the ad-
dition products in good yield with lower selectivities (entries 13
and 14). Finally reaction was carried out with 5d and 1a giving 6o in
37% with a 76:24 diastereoisomeric ratio (entry 15). This modest
yield might be easily explained by the low stability of 5d, due to the
presence of the para-methoxy substituent.
9
1a
1w
1x
1a
5b
5b
5b
5c
40 (50:50)
70 (42:58)
50 (50:50)
62 (82:18)
10
11
12
Finally, in order to define a plausible reaction pathway and
transition state the reaction with (E)-5a was carried out.
Under standard condition, the addition product was isolated in
75% as a 78:22 diastereoisomeric mixture. Interestingly, 1H NMR
has revealed that the major diastereoisomer was the anti isomer
(Fig. 4). Taking this result into account, we proposed a plausible
equilibration of the organo-indium species in favor of the ther-
modynamically stable Z isomer.21 This most stable species would
react through a six-membered ring transition state. The indium
metal center coordinates to the aldehyde and according to a chair
13
14
1w
1x
5c
5c
78 (61:39)
64 (66:34)
like intermediate the addition occurs at the g-position delivering
the anti-product as a major isomer, whatever the geometry of the
starting bromofluorinated allylic species (Fig. 5). Noteworthy, the
equatorial-equatorial gauche interaction in the favored transition
state might explain the observed selectivity. Indeed, better selec-
tivities were obtained in the case of aryl or vinyl substituted

G. Lemonnier et al. / Tetrahedron 70 (2014) 3123e3133
3127
Table 5 (continued )
agreement with the obtained crystal structure we proposed a six-
membered ring transition state.
Entry
Starting material
5
Major product
Yield %b ()c
37 (76:24)
4. Experimental section
15
1a
5d
4.1. Materials and instrumentation
a
Conditions: 1 (1 equiv), 5 (1 equiv), In(0) (1 equiv), EtOH (0.3 M), 50 ꢁC, 16 h.
Isolated yield of the diastereoisomeric mixture.
All reactions were carried out using an oven-dried glassware
using standard Schlenk technique unless otherwise stated. Flash
chromatography was performed with silica gel (0.040e0.060 nm).
Analytical thin layer chromatography was performed on silica gel
aluminum plates with F-254 indicator and visualized by UV light
(254 nm) and/or chemical staining with KMnO4 solution or PMA
b
c
anti:syn ratio determined by 19F NMR on the crude reaction mixture.
substrates, while the use of aliphatic one gave lower selectivities.
This difference might be explained thanks to this gauche in-
teraction in the course of the addition through a six members
transition state.
solution. 1H NMR spectra were recorded on a Bruker DXP 300, 13
NMR spectra at 75 MHz and 19F NMR spectra at 282 MHz. Chemical
C
shifts (d) are quoted in parts per million (ppm) relative to residual
solvent (CHCl3:
external CFCl3:
d
¼7.27 ppm for 1H,
d
¼77.0 ppm for 13C or relative to
d
¼0 ppm for 19F). The following abbreviations have
been used:
d (chemical shift), J (coupling constant), s (singlet), br s
(broad singlet), d (doublet), dd (doublet of doublets), ddd (doublet
of doublet of doublets), t (triplet), q (quartet), dq (doublet of
quartets), m (multiplet). High-resolution mass spectra (HRMS)
were recorded on Waters LCT Premier, IR spectra were recorded on
a PerkinElmer Spectrum 100. Melting points are uncorrected.
Fluoroacrylates 3aed were synthesized according to the litera-
ture procedure18 and 3-chloro-2-fluoroprop-1-ene was purchased
from Apollo Chemical. All aldehydes and ketones were recrystal-
lized, distilled or filtered through basic alumina prior-to-use.
Fig. 4. Reaction with (E)-fluorinated olefins.
4.2. Procedure
4.2.1. General procedure A for the allylation of aldehydes and ketones
with 3-chloro-2-fluoroprop-1-ene. In a 1.5 mL vial, indium (23 mg,
0.2 mmol), 1 (0.1 mmol) and solvent (1 mL) were added. Then, 3-
chloro-2-fluoroprop-1-ene (18 mL, 0.2 mmol) was added and the
vial was sealed (screwed cap). The resulting mixture was stirred at
the given temperature for 16 h, DCM was added and the aqueous
phase was extracted two times. Organic layer was dried over MgSO4
and the residue was purified by flash chromatography (SiO2, pe-
troleum ether/ethyl acetate mixture) to afford the corresponding
fluorinated alcohol 2 (see Table 2).
4.2.2. General procedure B for the reduction of fluoroacrylates 3 into
homoallylic alcohols 4. To a solution of fluoroacrylate 3 (11 mmol)
in THF (40 mL) at 0 ꢁC was added LiBH4 (44 mmol) and reaction was
stirred at rt for 6 h. The solution was carefully quenched with NH4Cl
(saturated aqueous solution) and extracted with EtOAc (three
times). The combined organic layer was washed with brine, dried
over MgSO4 and concentrated. The residue was purified by flash
chromatography (SiO2, petroleum ether/EtOAc mixture) to afford
the corresponding fluorinated allylic alcohol 4 (see Table 3).
Fig. 5. Proposed transition state.
4.2.3. General procedure C for the bromination of homoallylic alco-
hols 4. To a solution of alcohol 4 (6.6 mmol) in Et2O (20 mL) at 0 ꢁC
was added PBr3 (3.3 mmol). The resulting mixture was allowed to
reach to rt and stirred for 2 h. The reaction mixture was quenched
with NaHCO3 (saturated aqueous solution) and extracted with Et2O
(three times). The combined organic layer was washed with brine,
dried over MgSO4 and concentrated. The residue was purified by
flash chromatography (SiO2, petroleum ether/EtOAc mixture) to
afford the corresponding fluorinated bromo allylic derivative 5 (see
Table 3).
3. Conclusion
As summary, we developed herein a straightforward access to
fluorinated homoallylic alcohol by means of an indium promoted
allylation reaction. The synthesis and the use of
fluorinated allylic derivatives afforded the -addition products,
which have been isolated in good yields and moderate to good
diastereoselectivities. An X-ray analysis of the major product
revealed that the process furnished predominantly the anti-addi-
tion product. This methodology represents the first selective access
to the anti adducts in good to excellent yields. The reaction scope is
quite broad and the process is functional group tolerant. Finally, to
explain the stereochemical outcome of the reaction and in
g-substituted halo-
g
4.2.4. General procedure D for the allylation of aldehydes with 5. In
a vial, 5 (0.3 mmol), indium (0.3 mmol), 1 (0.3 mmol) and EtOH
(1 mL) were introduced, the vial was sealed (screwed caps) and

3128
G. Lemonnier et al. / Tetrahedron 70 (2014) 3123e3133
heated at 50 ꢁC under vigorous stirring for 16 h. The solution was
quenched with five drops NH4Cl (saturated aqueous solution) and
stirred for 10 min. The mixture was filtered throw a pad of Celite
(washed with DCM) and concentrated. The residue was purified by
flash chromatography (SiO2, cyclohexane/EtOAc mixture) to afford
the corresponding fluorinated alcohol 6 (see Table 5).
17 Hz). IR (cmꢀ1): 2918, 1673, 748, 697. Anal. Calcd for C13H15FO: C,
75.70; H, 7.33. Found: C, 75.79; H, 7.13.
4.3.7. 3-Fluoro-1-(thiophen-2-yl)but-3-en-1-ol 2g (Table 2, entry
7). Procedure A. 1H NMR (300 MHz, CDCl3)
d
7.19 (d, J¼5.1 Hz, 1H),
6.98e6.85 (m, 2H), 5.15 (t, J¼6.6 Hz, 1H), 4.60 (dd, J¼17.3, 2.9 Hz,
1H), 4.31 (dd, J¼49.9, 2.7 Hz, 1H), 2.79e2.56 (m, 2H), 2.25 (br s, 1H).
4.3. Physical and spectral datas
13C NMR (75 MHz, CDCl3)
d
162.6 (d, J¼257 Hz), 146.7, 126.7, 124.9,
124.0, 93.2 (d, J¼19 Hz), 67.0, 42.4 (d, J¼26 Hz). 19F NMR (282 MHz,
4.3.1. 1-(4-Chlorophenyl)-3-fluorobut-3-en-1-ol 2a (Table 2, entry
CDCl3)
d
ꢀ96.2 (ddt, J¼50, 20, 17 Hz). IR (cmꢀ1): 3297, 2921, 1678,
1). Procedure A. 1H NMR (300 MHz, CDCl3)
d
7.36e7.27 (m, 4H),
1057. Anal. Calcd for C8H9FOS: C, 55.79; H, 5.27; S, 18.62. Found: C,
55.56; H, 4.95; S, 18.43.
4.98e4.87 (m, 1H), 4.65 (dd, J¼17.3, 2.9 Hz, 1H), 4.33 (dd, J¼49.9,
2.9 Hz, 1H), 2.69e2.48 (m, 2H), 2.26 (d, J¼2.5 Hz, 1H). 13C NMR
(75 MHz, CDCl3)
d
162.9 (d, J¼257 Hz), 141.6, 133.7, 128.8 (2C), 127.2
4.3.8. 3-Fluoro-1-(pyridin-3-yl)but-3-en-1-ol 2h (Table 2, entry
(2C), 93.2 (d, J¼19 Hz), 70.4, 42.4 (d, J¼26 Hz). 19F NMR (282 MHz,
8). Procedure A. 1H NMR (300 MHz, CDCl3)
d 8.61 (s, 1H), 8.55 (d,
CDCl3)
d
ꢀ95.9 (ddt, J¼50, 21, 17 Hz). IR (cmꢀ1): 3375,1674,1046, 802.
J¼3.7 Hz, 1H), 7.74 (dt, J¼7.8, 1.8 Hz, 1H), 7.30 (dd, J¼7.8, 4.8 Hz, 1H),
5.02 (dd, J¼7.7, 5.6 Hz, 1H), 4.69 (dd, J¼17.2, 3.0 Hz, 1H), 4.36 (dd,
J¼49.8, 2.9 Hz, 1H), 2.81e2.55 (m, 2H), 2.44 (s, 1H). 13C NMR
Anal. Calcd for C10H10ClFO: C, 59.86; H, 5.02. Found: C, 59.80; H, 5.00.
4.3.2. Methyl 4-(3-fluoro-1-hydroxybut-3-enyl)benzoate 2b (Table 2,
(75 MHz, CDCl3)
d
162.6 (d, J¼257 Hz), 149.1, 147.6, 138.8, 133.8,
entry 2). Procedure A. 1H NMR (300 MHz, CDCl3)
d
8.01 (d, J¼8.1 Hz,
123.7, 93.5 (d, J¼19 Hz), 68.7, 42.4 (d, J¼26 Hz). 19F NMR (282 MHz,
2H), 7.43 (d, J¼8.3 Hz, 2H), 5.01 (t, J¼6.6 Hz, 1H), 4.65 (dd, J¼17.2,
2.9 Hz, 1H), 4.33 (dd, J¼49.8, 2.8 Hz, 1H), 3.90 (s, 3H), 2.67e2.52 (m,
CDCl3)
d
ꢀ96.0 (ddt, J¼50, 22, 17 Hz). IR (cmꢀ1): 2918, 1677, 1428,
855, 712. Anal. Calcd for C9H10FNO: C, 64.66; H, 6.03; N, 8.38.
Found: C, 65.01; H, 6.01; N, 8.35.
2H), 2.40 (s, 1H). 13C NMR (75 MHz, CDCl3)
d 166.9, 162.7 (d,
J¼257 Hz), 148.1, 129.9 (2C), 129.6, 125.6 (2C), 93.2 (d, J¼19 Hz),
70.4, 52.2 (d, J¼3 Hz), 42.3 (d, J¼26 Hz). 19F NMR (282 MHz, CDCl3)
4.3.9. 1-(2-Amino-4,6-dichloropyrimidin-5-yl)-3-fluorobut-3-en-1-ol
d
ꢀ96.0 (dq, J¼50, 18 Hz). IR (cmꢀ1): 3473, 1696, 1671, 1286, 765,
2i (Table 2, entry 9). Procedure A. 1H NMR (300 MHz, CDCl3)
d 5.56 (s,
704, 537. Anal. Calcd for C12H13FO3: C, 64.28; H, 5.84. Found: C,
64.64; H, 5.82.
2H), 5.53e5.42 (m, 1H), 4.65 (d, J¼16.9 Hz, 1H), 4.39 (d, J¼49.2 Hz,
1H), 2.96 (ddd, J¼22.6,14.5, 8.2 Hz,1H), 2.85e2.68 (m,1H), 2.67 (br s,
1H). 13C NMR (75 MHz, CDCl3)
d
162.2 (d, J¼258 Hz),161.5 (2C),160.4,
4.3.3. 3-Fluoro-1-phenylbut-3-en-1-ol
2c
(Table
7.42e7.27 (m, 5H),
2,
entry
119.8, 93.5 (d, J¼17 Hz), 67.1 (d, J¼2 Hz), 38.3 (d, J¼27 Hz). 19F NMR
3). Procedure A. 1H NMR (300 MHz, CDCl3)
d
(282 MHz, CDCl3)
d
ꢀ96.0 (dq, J¼50, 17 Hz). IR (cmꢀ1): 3320, 1637,
5.03e4.90 (m, 1H), 4.66 (dd, J¼17.3, 2.7 Hz, 1H), 4.35 (dd, J¼50.0,
1567, 1505, 806, 444. Anal. Calcd for C8H8Cl2FN3O: C, 38.12; H, 3.20;
N, 16.67. Found: C, 37.78; H, 3.34; N, 16.97.
2.5 Hz, 1H), 2.75e2.53 (m, 2H), 2.17 (br s, 1H). 13C NMR (75 MHz,
CDCl3)
d
163.3 (d, J¼257 Hz), 143.2, 128.7 (2C),128.1, 125.8 (2C), 93.0
(d, J¼19 Hz), 71.0, 42.4 (d, J¼26 Hz). 19F NMR (282 MHz, CDCl3)
4.3.10. 3-Fluoro-1-ferrocenylbut-3-en-1-ol 2j (Table 2, entry
d
ꢀ95.9 (ddt, J¼50, 21, 17 Hz). IR (cmꢀ1): 3375, 1674, 852, 756, 698.
10). Procedure A. 1H NMR (300 MHz, CDCl3)
d
4.63e4.49 (m, 2H),
4.39e4.17 (m, 1H), 4.20 (s, 1H), 4.16e4.04 (m, 8H), 2.58e2.37 (m,
2H), 2.08 (br s, 1H). 13C NMR (75 MHz, CDCl3)
163.7 (d, J¼257 Hz),
Anal. Calcd for C10H11FO: C, 72.27; H, 6.67. Found: C, 72.25; H, 6.68.
d
4.3.4. 3-Fluoro-1-(4-methoxyphenyl)but-3-en-1-ol 2d (Table 2, entry
92.6, 92.3 (d, J¼20 Hz), 68.6 (5C), 68.3, 68.2, 67.1, 66.6, 65.6, 41.2 (d,
4). Procedure A. 1H NMR (300 MHz, CDCl3)
d
7.29 (d, J¼8.5 Hz, 2H),
J¼26 Hz). 19F NMR (282 MHz, CDCl3)
d
ꢀ95.4 (m). IR (cmꢀ1): 3099,
6.89 (d, J¼8.5 Hz, 2H), 4.90 (dd, J¼8.3, 5.1 Hz, 1H), 4.63 (dd, J¼17.4,
2922, 1673, 849, 816, 477. Anal. Calcd for C14H15FFeO: C, 61.34; H,
5.52. Found: C, 61.12; H, 5.72.
2.7 Hz, 1H), 4.33 (dd, J¼50.1, 2.5 Hz, 1H), 3.80 (s, 3H), 2.75e2.45 (m,
2H), 2.20 (br s, 1H). 13C NMR (75 MHz, CDCl3)
d
163.3 (d, J¼257 Hz),
159.3, 135.3, 127.0 (2C), 113.9 (2C), 92.7 (d, J¼19 Hz), 70.5, 55.3 (d,
4.3.11. 5-Fluoro-1-phenylhex-5-en-3-ol (Table
2k
2,
entry
J¼3 Hz), 42.2 (d, J¼26 Hz). 19F NMR (282 MHz, CDCl3)
d
ꢀ95.7 (dddd,
11). Procedure A. 1H NMR (300 MHz, CDCl3)
d 7.31e7.17 (m, 2H),
J¼50, 22,17,15 Hz). IR (cmꢀ1): 2909,1675,1511,1241, 828. Anal. Calcd
7.17e7.03 (m, 3H), 4.58 (dd, J¼17.4, 2.8 Hz, 1H), 4.27 (dd, J¼50.1,
2.7 Hz, 1H), 3.92e3.69 (m, 1H), 2.83e2.69 (m, 1H), 2.69e2.54 (m,
1H), 2.46e2.13 (m, 2H),1.82e1.66 (m, 2H). 13C NMR (75 MHz, CDCl3)
for C11H13FO2: C, 67.33; H, 6.68. Found: C, C, 67.62; H, 6.69.
4.3.5. 3-(3-Fluoro-1-hydroxybut-3-enyl)phenol 2e (Table 2, entry
d
163.7 (d, J¼257 Hz), 141.8, 128.60 (2C), 128.56 (2C), 126.1, 92.8 (d,
5). Procedure A. 1H NMR (300 MHz, CDCl3)
d
7.29e7.18 (m, 1H),
J¼20 Hz), 68.0, 40.5 (d, J¼26 Hz), 38.5, 32.1. 19F NMR (282 MHz,
6.98e6.85 (m, 2H), 6.76 (dd, J¼8.0, 2.5 Hz, 1H), 4.96 (br s, 1H),
4.96e4.86 (m, 1H), 4.66 (dd, J¼17.4, 2.8 Hz, 1H), 4.35 (dd, J¼50.0,
2.8 Hz, 1H), 2.72e2.49 (m, 2H), 2.02 (br s, 1H). 13C NMR (75 MHz,
CDCl3)
d
ꢀ94.5 (dddd, J¼50, 24, 17, 16 Hz). IR (cmꢀ1): 3376, 2922,
1673, 848, 698. Anal. Calcd for C12H15FO: C, 74.20; H, 7.78. Found: C,
74.41; H, 7.75.
CDCl3)
d
163.1 (d, J¼257 Hz), 155.8, 145.0, 129.9, 118.1, 114.8, 112.5,
92.9 (d, J¼19 Hz), 70.6, 42.2 (d, J¼26 Hz). 19F NMR (282 MHz, CDCl3)
4.3.12. 2-Fluorododec-1-en-4-ol 2l (Table 2, entry 12). Procedure A.
d
ꢀ96.0 (dddd, J¼34, 21, 20, 17 Hz). IR (cmꢀ1): 3327, 3077, 2921,
1H NMR (300 MHz, CDCl3)
d
4.64 (dd, J¼17.4, 2.7 Hz, 1H), 4.35 (dd,
1464, 1030, 854. Anal. Calcd for C10H11FO2: C, 65.92; H, 6.09. Found:
C, 65.59; H, 6.00.
J¼50.1, 2.7 Hz, 1H), 3.93e3.77 (m, 1H), 2.47e2.15 (m, 2H), 1.55-1.40
(m, 2H), 1.38e1.17 (m, 12H), 0.88 (t, J¼6.6 Hz, 3H). 13C NMR
(75 MHz, CDCl3)
d
164.0 (d, J¼258 Hz), 92.5 (d, J¼22 Hz), 68.5, 40.3
4.3.6. (E)-5-Fluoro-2-methyl-1-phenylhexa-1,5-dien-3-ol 2f (Table 2,
(d, J¼27 Hz), 36.8, 31.9, 29.7, 29.5, 29.2, 25.5, 22.7, 14.1. 19F NMR
entry 6). Procedure A. 1H NMR (300 MHz, CDCl3)
d
1H NMR
(282 MHz, CDCl3)
3346, 2943, 1215, 1018, 838, 702. Anal. Calcd for C12H23FO: C, 71.24;
H, 11.46. Found: C, 70.92; H, 11.54.
d
ꢀ94.6 (dddd, J¼50, 24, 17, 15 Hz). IR (cmꢀ1):
(300 MHz, CDCl3)
2.4 Hz, 1H), 4.46e4.21 (m, 2H), 2.56e2.34 (m, 2H), 2.01 (s, 1H), 1.82
(s, 3H). 13C NMR (75 MHz, CDCl3)
163.4 (d, J¼257 Hz), 138.7, 137.2,
d
7.32e7.08 (m, 5H), 6.50 (s, 1H), 4.60 (dd, J¼17.3,
d
129.0 (2C), 128.2 (2C), 126.6, 126.4, 92.6 (d, J¼19 Hz), 74.3, 38.7 (d,
4.3.13. (6S)-2-Fluoro-6,10-dimethylundeca-1,9-dien-4-ol 2m (Table
2, entry 13). Procedure A. Mixture 50:50 of diastereoisomers. 1H
J¼26 Hz), 13.4. 19F NMR (282 MHz, CDCl3)
d
ꢀ95.4 (ddt, J¼50, 21,

G. Lemonnier et al. / Tetrahedron 70 (2014) 3123e3133
3129
NMR (300 MHz, CDCl3)
d
5.03 (t, J¼6.9 Hz, 1H), 4.58 (dd, J¼17.4,
Anal. Calcd for C19H29F2NO7: C, 54.15; H, 6.94; N, 3.32. Found: C,
53.75; H, 6.89; N, 3.61.
1.5 Hz, 1H), 4.28 (d, J¼50.3 Hz, 1H), 3.92 (br s, 1H), 2.44e2.04 (m,
2H), 2.05e1.81 (m, 2H), 1.78e1.57 (m, 1H), 1.61 (s, 3H), 1.53 (s, 3H),
1.46e1.21 (m, 3H), 1.23e1.01 (m, 2H), 0.92e0.71 (m, 3H). 13C NMR
4.3.18. 4-Fluoro-2-phenylpent-4-en-2-ol 2r (Table 2, entry
(75 MHz, CDCl3)
d
164.0 (d, J¼257 Hz), 131.52 (0.5C), 131.46 (0.5C),
18). Procedure A. 1H NMR (300 MHz, CDCl3)
d
7.39 (d, J¼7.9 Hz,
124.8, 92.9e92.3 (m), 66.7 (0.5C), 66.3 (0.5C), 44.4 (0.5C), 44.3
(0.5C), 41.2 (d, J¼26 Hz, 0.5C), 40.7 (d, J¼26 Hz, 0.5C), 37.9 (0.5C),
36.7 (0.5C), 29.4 (0.5C), 29.0 (0.5C), 25.9, 25.6 (0.5C), 25.4 (0.5C),
2H), 7.28 (t, J¼7.5 Hz, 2H), 7.19 (t, J¼7.2 Hz, 1H), 4.56 (dd, J¼17.5,
2.2 Hz, 1H), 4.17 (dd, J¼50.1, 2.3 Hz, 1H), 2.75e2.50 (m, 2H), 2.20
(d, J¼2.1 Hz, 1H), 1.55 (s, 3H). 13C NMR (75 MHz, CDCl3)
d 163.3 (d,
20.3 (0.5C), 19.2 (0.5C), 17.8. 19F NMR (282 MHz, CDCl3)
d
ꢀ94.5 (m,
J¼258 Hz), 146.8, 128.2 (2C), 127.0, 124.6 (2C), 94.2 (d, J¼20 Hz),
0.5F), ꢀ94.6 (m, 0.5F). IR (cmꢀ1): 3353, 2917, 1673, 845. Anal. Calcd
73.3 (d, J¼3 Hz), 46.6 (d, J¼24 Hz), 29.6. 19F NMR (282 MHz,
for C13H23FO: C, 72.85; H, 10.82. Found: C, 73.23; H, 11.13.
CDCl3)
d
ꢀ89.6 (dq, J¼50, 20 Hz). IR (cmꢀ1): 3392, 2928, 1674,
1167, 854. Anal. Calcd for C11H13FO: C, 73.31; H, 7.27. Found: C,
73.34 H, 7.53.
4.3.14. 2-Fluoro-10-methoxy-6,10-dimethylundec-1-en-4-ol
(Table 2, entry 14). Procedure A. Mixture 50:50 of di-
astereoisomers. 1H NMR (300 MHz, CDCl3)
4.70e4.57 (m, 1H),
2n
d
4.3.19. 1,1,1,4-Tetrafluoro-2-phenylpent-4-en-2-ol 2s (Table 2, entry
4.41e4.26 (m, 1H), 4.01e3.87 (m, 1H), 3.17 (s, 3H), 2.47e2.14 (m,
2H), 1.78e1.57 (m, 1H), 1.55e1.17 (m, 9H), 1.13 (s, 6H), 1.00e0.88
19). Procedure A. 1H NMR (300 MHz, CDCl3)
d
7.58 (d, J¼7.0 Hz, 2H),
7.47e7.33 (m, 3H), 4.66 (dd, J¼17.4, 2.7 Hz, 1H), 4.31 (dd, J¼49.8,
(m, 3H). 13C NMR (75 MHz, CDCl3)
d
163.8 (d, J¼257 Hz), 92.4 (d,
2.8 Hz, 1H), 3.24 (br s, 1H), 3.19e2.93 (m, 2H). 13C NMR (75 MHz,
J¼19 Hz), 74.7, 66.6 (0.5C), 66.2 (0.5C), 49.1, 44.4 (0.5C), 44.2
(0.5C), 41.1 (d, J¼26 Hz, 0.5C), 40.6 (d, J¼26 Hz, 0.5C), 40.0, 38.3
(0.5C), 36.9 (0.5C), 29.5 (0.5C), 29.2 (0.5C), 25.0, 24.9, 21.2 (0.5C),
21.0 (0.5C), 20.2 (0.5C), 19.1 (0.5C). 19F NMR (282 MHz, CDCl3)
CDCl3)
d
160.3 (d, J¼257 Hz), 135.9, 128.8, 128.3 (2C), 126.3 (2C),
125.0 (q, J¼286 Hz), 95.9 (d, J¼19 Hz), 76.0 (qd, J¼28, 2 Hz), 38.6 (d,
J¼25 Hz). 19F NMR (282 MHz, CDCl3)
ꢀ79.6 (m, 3F), ꢀ90.7 (m). IR
d
(cmꢀ1): 3346, 2945, 1674, 1167, 1018, 851, 701. Anal. Calcd for
d
ꢀ94.47 (m, 0.5F), ꢀ94.52 (m, 0.5F). IR (cmꢀ1): 2938, 1676, 1080,
C11H10F4O: C, 56.41; H, 4.30. Found: C, 56.65; H, 4.45.
847, 737. Anal. Calcd for C14H27FO2: C, 68.25; H, 11.05. Found: C,
68.37; H, 10.98.
4.3.20. 1,1,1,5-Tetrafluoro-3-phenylhex-5-en-3-ol 2t (Table 2, entry
20). Procedure A. 1H NMR (300 MHz, CDCl3)
7.33e7.10 (m, 5H),
d
4.3.15. (S)-Menthyl 4-fluoro-2-hydroxypent-4-enoate 2o (Table 2,
4.68 (dd, J¼17.3, 2.6 Hz, 1H), 4.34 (dd, J¼49.6, 2.5 Hz, 1H), 3.09 (d,
entry 17). Procedure A. 1H NMR (300 MHz, CDCl3)
d 4.90e4.51 (m,
J¼14.2 Hz, 1H), 2.89 (d, J¼14.2 Hz, 1H), 2.69e2.26 (m, 3H). 13C NMR
1.5H), 4.42 (br s, 0.5H), 4.26 (br s, 0.5H), 4.03 (br s, 0.5H),
3.05e2.89 (m, 1H), 2.78e2.35 (m, 2H), 2.06e1.86 (m, 1H),
1.85e1.69 (m, 1H), 1.69e1.54 (m, 2H), 1.52e1.25 (m, 2H), 1.25e1.08
(s, 1H), 1.13e0.90 (m, 2H), 0.90e0.76 (m, 7H), 0.76e0.61 (m, 3H).
(75 MHz, CDCl3)
d
161.1 (d, J¼257 Hz), 133.9, 131.1 (2C), 128.6 (2C),
127.5, 125.7 (q, J¼287 Hz), 95.5 (d, J¼20 Hz), 74.9 (qd, J¼27, 3 Hz),
39.8, 36.9 (d, J¼25 Hz). 19F NMR (282 MHz, CDCl3)
d
ꢀ78.9 (m, 3F),
ꢀ91.5 (m). IR (cmꢀ1): 3360, 2942, 1674, 1164, 853, 701. Anal. Calcd
13C NMR (75 MHz, CDCl3)
d
173.5 (0.5C), 173.5 (0.5C), 161.84 (d,
for C12H12F4O: C, 58.07; H, 4.87. Found: C, 57.84; H, 5.07.
J¼257 Hz, 0.5C), 161.79 (d, J¼257 Hz, 0.5C), 93.6e92.9 (m), 76.4
(0.5C), 75.9 (0.5C), 67.5 (0.5C), 67.2 (0.5C), 46.9, 40.8 (0.5C), 40.6
(0.5C), 37.3 (d, J¼27 Hz, 0.5C), 37.0 (d, J¼27 Hz, 0.5C), 34.1, 31.4,
4.3.21. (Z)-(3-Bromo-2-fluoroprop-1-enyl)benzene 5a (Table 3, entry
1). Following procedure C, 5a was obtained as a yellow oil in 88%
yield, after flash chromatography (SiO2, cyclohexane/EtOAc, 90:10,
Rf¼0.70 cyclohexane/EtOAc 8:2). 1H NMR (300 MHz, CDCl3)
26.2, 23.3, 22.0, 20.7, 16.3. 19F NMR (282 MHz, CDCl3)
d
ꢀ95.7 (m,
0.5F), ꢀ96.1 (m, 0.5F). IR (cmꢀ1): 2955, 2926, 2872, 1731, 1214,
1094. Anal. Calcd for C15H25FO3: C, 66.15; H, 9.25. Found: C, 68.01;
H, 11.01.
d
7.58e7.31 (m, 5H), 5.90 (d, J¼36.0 Hz, 1H), 4.14 (d, J¼20.1 Hz, 2H).
13C NMR (75 MHz, CDCl3)
d
154.5 (d, J¼263 Hz), 132.3 (d, J¼3 Hz),
129.1, 128.9, 128.7, 128.3, 128.2, 110.5 (d, J¼8 Hz), 29.7 (d, J¼31 Hz).
4.3.16. (ꢂ)-(trans)-Methyl 1-(bis(tert-butoxycarbonyl)amino)-2-
fluoro-2-(3-fluoro-1-hydroxybut-3-enyl)cyclopropanecarboxylate 2p
19F NMR (282 MHz, CDCl3)
d
ꢀ108.3 (dt, J¼36, 20 Hz). IR (cmꢀ1):
3027, 1681, 1422, 1351, 1205, 904, 690. Anal. Calcd for C9H8BrF: C,
50.26; H, 3.75. Found: C, 50.45; H, 3.59.
(Table 2, entry 15). Procedure A. 1H NMR (300 MHz, CDCl3)
d 4.64
(dd, J¼17.2, 2.8 Hz, 1H), 4.42 (dd, J¼49.7, 2.8 Hz, 1H), 4.35 (dtd,
J¼28.0, 7.1, 2.1 Hz,1H), 3.94 (d, J¼2.6 Hz, 1H), 3.77 (s, 3H), 2.79e2.57
(m, 2H), 2.23 (dd, J¼18.1, 8.8 Hz, 1H), 1.81 (dd, J¼22.6, 8.8 Hz, 1H),
4.3.22. (Z)-(5-Bromo-4-fluoropent-3-enyl)benzene 5b (Table 3, entry
2). Following procedure C, 5b was obtained as a yellow oil in 50%
yield, after flash chromatography (SiO2, cyclohexane/EtOAc, 90:10,
Rf¼0.78 cyclohexane/EtOAc 8:2). 1H NMR (300 MHz, CDCl3)
1.53 (s, 9H), 1.49 (s, 9H). 13C NMR (75 MHz, CDCl3)
d 169.1, 162.9 (d,
J¼256 Hz), 153.9, 151.5, 92.5 (d, J¼23 Hz), 86.3 (d, J¼237 Hz), 84.4,
83.4, 66.5 (d, J¼20 Hz), 53.2 (d, J¼4 Hz), 44.3 (d, J¼9 Hz), 35.8 (d,
J¼26 Hz), 27.9 (6C), 27.1 (d, J¼9.1 Hz). 19F NMR (282 MHz, CDCl3)
d
7.40e7.13 (m, 5H), 5.01 (dt, J¼34.3, 7.5 Hz, 1H), 3.94 (d, J¼19.6 Hz,
2H), 2.72 (t, J¼7.6 Hz, 2H), 2.47 (m, 2H). 13C NMR (75 MHz, CDCl3)
d
ꢀ95.6 (m), ꢀ190.1 (dddd, J¼28, 22, 18, 2 Hz). IR (cmꢀ1): 3480,
d
154.6 (d, J¼251 Hz), 141.2, 128.64 (2C), 128.61 (2C), 126.3, 110.3 (d,
2980, 1735, 1678, 1120. Anal. Calcd for C19H29F2NO7: C, 54.15; H,
6.94; N, 3.32. Found: C, 54.38; H, 7.02; N, 3.62.
J¼15 Hz), 35.1 (d, J¼1 Hz), 28.8 (d, J¼32 Hz), 25.9 (d, J¼3 Hz). 19
F
NMR (282 MHz, CDCl3)
3027, 1691, 1454, 1233, 697. Anal. Calcd for C11H12BrF: C, 54.34; H,
4.98. Found: C, 53.25; H, 5.07.
d
ꢀ114.5 (dtt, J¼34, 19, 1 Hz). IR (cmꢀ1):
4.3.17. (ꢂ)-(trans)-Methyl 1-(bis(tert-butoxycarbonyl)amino)-2-
fluoro-2-(3-fluoro-1-hydroxybut-3-enyl)cyclopropanecarboxylate 2q
(Table 2, entry 16). Procedure A. 1H NMR (300 MHz, CDCl3)
4.3.23. (Z)-1-Bromo-4-(3-bromo-2-fluoroprop-1-enyl)benzene
5c
d
5.18e4.96 (m, 2H), 4.74 (dd, J¼17.0, 3.0 Hz, 1H), 4.45 (dd, J¼49.6,
(Table 3, entry 3). Following procedure C, 5c was obtained as
a colorless oil in 91% yield, after flash chromatography (SiO2, cy-
clohexane/EtOAc, 90:10, Rf¼0.73 cyclohexane/EtOAc 8:2). 1H NMR
3.0 Hz, 1H), 3.75 (s, 3H), 3.00e2.67 (m, 2H), 2.46 (dd, J¼20.8, 8.2 Hz,
1H), 1.71 (dd, J¼13.2, 8.3 Hz, 1H), 1.49 (s, 9H), 1.44 (s, 9H). 13C NMR
(75 MHz, CDCl3)
d
168.0, 161.3 (d, J¼254 Hz), 155.5, 152.9, 94.1 (d,
(300 MHz, CDCl3)
d
7.49 (d, J¼8.3 Hz, 2H), 7.38 (d, J¼8.2 Hz, 2H),
J¼17 Hz), 83.9 (d, J¼240 Hz), 83.3, 81.0, 73.3 (d, J¼21 Hz), 52.9 (d,
J¼4 Hz), 43.5 (d, J¼10 Hz), 33.4 (dd, J¼28, 6 Hz), 29.7, 28.2 (3C), 27.7
5.82 (d, J¼35.6 Hz, 1H), 4.12 (d, J¼20.2 Hz, 2H). 13C NMR (75 MHz,
CDCl3)
d
155.0 (d, J¼264 Hz), 131.8 (2C), 131.2 (d, J¼4 Hz), 130.5,
(3C). 19F NMR (282 MHz, CDCl3)
d
ꢀ95.8 (ddddd, J¼50, 26, 17, 11,
130.4, 122.1, 109.4 (d, J¼8 Hz), 29.4 (d, J¼31 Hz). 19F NMR (282 MHz,
1 Hz), ꢀ190.5 (dt, J¼22, 12 Hz). IR (cmꢀ1): 2921, 1739, 1249, 1157.
CDCl3)
d
ꢀ106.9 (dt, J¼35, 20 Hz). IR (cmꢀ1): 1676, 1486, 1235, 1159,

3130
G. Lemonnier et al. / Tetrahedron 70 (2014) 3123e3133
1008, 857, 808, 661. Anal. Calcd for C9H7Br2F: C, 36.77; H, 2.40.
Found: C, 36.55; H, 2.50.
d
165.1 (d, J¼262 Hz),147.5,147.0,137.4 (d, J¼2 Hz),135.3,128.5,128.4,
128.4 (2C), 127.3, 120.6, 107.8, 106.9, 100.9, 93.0 (d, J¼20 Hz), 74.8 (d,
J¼3 Hz), 57.7 (d, J¼24 Hz). 19F NMR (282 MHz, CDCl3)
ꢀ101.6 (ddd,
d
4.3.24. (Z)-1-(3-Bromo-2-fluoroprop-1-enyl)-4-methoxybenzene 5d
(Table 3, entry 4). Following procedure C, 5d was obtained as
a crude colorless oil in 84% yield (Rf¼0.68 cyclohexane/EtOAc 8:2).
The compound was unstable on SiO2. 1H NMR (300 MHz, CDCl3)
J¼50, 25, 18 Hz). IR (cmꢀ1): 3028, 2897, 1670, 1487, 1442, 1240, 1034.
Anal. Calcd for C17H15FO3: C, 71.32; H, 5.28. Found: C, 71.13; H, 5.39.
Compound 6c syn: Rf¼0.32 cyclohexane/EtOAc 8:2. 1H NMR
(300 MHz, CDCl3)
d 7.36e7.20 (m, 5H), 6.83e6.66 (m, 3H), 5.86 (s,
d
7.49 (d, J¼8.4 Hz, 2H), 6.90 (d, J¼8.5 Hz, 2H), 5.84 (d, J¼36.4 Hz,
2H), 5.03 (d, J¼8.6 Hz, 1H), 4.37 (dd, J¼17.9, 3.0 Hz, 1H), 4.15 (dd,
1H), 4.15 (d, J¼20.4 Hz, 2H), 3.84 (s, 3H). 13C NMR (75 MHz, CDCl3)
J¼50.2, 3.1 Hz, 1H), 3.54 (dd, J¼24.3, 8.8 Hz, 2H). 13C NMR (75 MHz,
d
159.4, 153.1 (d, J¼260 Hz), 130.5, 130.4, 125.0 (d, J¼4 Hz), 114.0
CDCl3)
d
164.7 (d, J¼260 Hz),147.7,147.2,137.3 (d, J¼2 Hz),135.6,128.9
(2C), 110.2 (d, J¼8 Hz), 55.3, 30.3 (d, J¼31 Hz). 19F NMR (282 MHz,
(2C), 128.8, 128.8, 127.8, 120.3, 108.0, 106.9, 101.1, 92.7 (d, J¼19 Hz),
CDCl3)
d
ꢀ111.3 (dt, J¼36, 20 Hz). IR (cmꢀ1): 1679, 1606, 1510, 1463,
74.3, 58.0 (d, J¼24 Hz). 19F NMR (282 MHz, CDCl3)
d
ꢀ101.1 (ddd,
1237, 1176, 1154, 1029.
J¼50, 24, 18 Hz). IR (cmꢀ1): 3027, 2893, 1669, 1487, 1442, 1241, 1034.
Anal. Calcd for C17H15FO3: C, 71.32; H, 5.28. Found: C, 71.61; H, 5.41.
4.3.25. 1-(4-Chlorophenyl)-3-fluoro-2-phenylbut-3-en-1-ol 6a (Table
5, entry 1). Following procedure D, 6a was obtained as the pure
anti (white solid) and the pure syn (colorless oil) diastereomers, after
flash chromatography (SiO2, cyclohexane/EtOAc, 95:5 to 65:35).
Compound 6a anti: Rf¼0.42 cyclohexane/EtOAc 8:2. 1H NMR
4.3.28. 3-Fluoro-2-phenyl-1-(thiophen-2-yl)but-3-en-1-ol 6d (Table
5,entry 4). Following procedure D, 6d was obtained as the pure
anti diastereomer (yellow oil) and the mixture of anti/syn di-
astereomers (yellow oil), after flash chromatography (SiO2, cyclo-
hexane/EtOAc, 95:5 to 70:30). Compound 6d anti: Rf¼0.41
(300 MHz, CDCl3)
d
7.16e6.91 (m, 9H), 4.99 (d, J¼9.4 Hz, 1H), 4.73
(dd, J¼17.8, 3.1 Hz, 1H), 4.55 (dd, J¼50.1, 3.1 Hz, 1H), 3.58 (dd, J¼24.8,
cyclohexane/EtOAc 8:2. 1H NMR (300 MHz, CDCl3)
d 7.31e7.13 (m,
9.4 Hz, 1H). 13C NMR (75 MHz, CDCl3):
d
164.7 (d, J¼258 Hz), 139.7,
6H), 6.85e6.74 (m, 1H), 6.66 (d, J¼3.4 Hz, 1H), 5.42 (dd, J¼9.4,
136.9, 133.5, 128.5, 128.4, 128.4, 128.3, 128.1, 127.4, 93.4 (d, J¼20 Hz),
3.2 Hz,1H), 4.82 (dd, J¼17.7, 3.1 Hz,1H), 4.67 (dd, J¼50.0, 3.1 Hz,1H),
74.4 (d, J¼3 Hz), 57.8 (d, J¼24 Hz). 19F NMR (282 MHz, CDCl3)
3.80 (dd, J¼24.9, 9.4 Hz, 1H). 13C NMR (75 MHz, CDCl3)
d 164.5 (d,
d
ꢀ101.6 (ddd, J¼50, 25, 18 Hz). IR (cmꢀ1): 3385, 2932, 1675, 1492,
J¼262 Hz), 144.9, 137.2 (d, J¼2 Hz), 128.5 (2C), 128.4, 128.4, 127.5,
1451, 1236, 1030, 1010. Anal. Calcd for C16H14ClFO: C, 69.44; H, 5.10.
126.4, 125.3, 124.9, 93.3 (d, J¼19 Hz), 70.9, 58.1 (d, J¼24 Hz). 19F
Found: C, 69.63; H, 5.25. Compound 6a syn: Rf¼0.51 cyclohexane/
NMR (282 MHz, CDCl3)
d
ꢀ102.4 (ddd, J¼50, 25, 18 Hz). IR (cmꢀ1):
EtOAc 8:2. 1H NMR (300 MHz, CDCl3)
d
7.35e7.22 (m, 9H), 5.12 (dd,
3411, 2922, 1670, 1248, 1034. Anal. Calcd for C14H13FOS: C, 67.72; H,
5.28; S, 12.91. Found: C, 667.75; H, 5.53; S, 13.00. Compound 6d syn:
Rf¼0.51 cyclohexane/EtOAc 8:2. 1H NMR (300 MHz, CDCl3)
J¼8.5, 2.6 Hz, 1H), 4.40 (dd, J¼17.9, 3.1 Hz, 1H), 4.16 (dd, J¼50.2,
3.1 Hz, 1H), 3.54 (dd, J¼23.9, 8.5 Hz, 1H).∙13C NMR (75 MHz, CDCl3)
d
164.4 (d, J¼260 Hz), 140.0, 136.8, 133.7, 128.9, 128.9, 128.8, 128.5,
d
7.40e7.22 (m, 6H), 6.96 (d, J¼3.3 Hz, 1H), 6.92e6.84 (m, 1H), 5.42
128.4, 128.2, 128.0, 127.9, 93.0 (d, J¼19 Hz), 73.8 (d, J¼1 Hz), 58.0 (d,
(dd, J¼8.5, 3.2 Hz, 1H), 4.45 (dd, J¼17.9, 3.1 Hz, 1H), 4.25 (dd, J¼50.2,
J¼23 Hz). 19F NMR (282 MHz, CDCl3)
ꢀ101.2 (ddd, J¼50, 24, 18 Hz).
d
3.1 Hz, 1H), 3.68 (dd, J¼22.9, 8.5 Hz, 1H). 13C NMR (75 MHz, CDCl3)
IR (cmꢀ1): 3270, 2973, 1670, 1492, 1243, 1047, 1012. Anal. Calcd for
d
164.5 (d, J¼261 Hz), 145.1, 136.9, 128.9 (4C), 127.9, 126.5, 125.3,
C16H14ClFO: C, 69.44; H, 5.10. Found: C, 69.79; H, 4.99.
125.1, 92.9 (d, J¼19 Hz), 70.6, 58.31 (d, J¼22 Hz). 19F NMR (282 MHz,
CDCl3)
d
ꢀ101.5 (ddd, J¼50, 23, 18 Hz). IR (cmꢀ1): 2921, 1670, 1494,
4.3.26. 3-Fluoro-2-phenyl-1-(3,4,5-trimethoxyphenyl)but-3-en-1-ol
6b (Table 5, entry 2). Following procedure D, 6b was obtained as
a mixture of anti/syn diastereomers (colorless oil), after flash
chromatography (SiO2, cyclohexane/EtOAc, 95:5 to 70:30, Rf¼0.14
cyclohexane/EtOAc 8:2). Compound 6b anti: 1H NMR (300 MHz,
1248, 1033. Anal. Calcd for C14H13FOS: C, 67.72; H, 5.28; S, 12.91.
Found: C, 68.00; H, 5.36; S, 13.13.
4.3.29. (E)-2-Fluoro-3-phenylhepta-1,5-dien-4-ol 6e (Table 5,entry
5). Following procedure D, 6e was obtained as the pure anti di-
astereomer (colorless oil) and the mixture of anti/syn di-
astereomers (colorless oil), after flash chromatography (SiO2,
cyclohexane/EtOAc, 95:5 to 70:30). Compound 6e anti: Rf¼0.44
CDCl3)
(dd, J¼17.8, 3.1 Hz, 1H), 4.54 (dd, J¼50.2, 3.1 Hz, 1H), 3.66 (s, 3H),
3.56 (s, 6H), 3.48 (m, 1H). 13C NMR (75 MHz, CDCl3)
165.1 (d,
d
7.33e6.91 (m, 5H), 6.17 (s, 2H), 4.89 (d, J¼9.5 Hz, 1H), 4.71
d
J¼262 Hz), 152.6, 137.5, 137.5, 137.0 (2C), 128.6, 128.5, 128.3 (2C),
cyclohexane/EtOAc 8:2. 1H NMR (300 MHz, CDCl3)
d 7.46e7.18 (m,
127.2, 103.5 (2C), 93.0 (d, J¼20 Hz), 75.0 (d, J¼3 Hz), 60.8, 58.0 (d,
5H), 5.72e5.53 (m, 1H), 5.50e5.31 (m, 1H), 4.76 (dd, J¼17.9, 2.9 Hz,
1H), 4.58 (dd, J¼50.3, 3.0 Hz, 1H), 4.55 (t, J¼7.5 Hz, 1H), 3.51 (dd,
J¼23.4, 8.5 Hz, 1H), 1.60 (d, J¼6.5 Hz, 3H). 13C NMR (75 MHz, CDCl3)
J¼24 Hz), 55.9, 55.9. 19F NMR (282 MHz, CDCl3)
ꢀ101.4 (ddd, J¼50,
d
25, 18 Hz). Compound 6b syn: 1H NMR (300 MHz, CDCl3)
d
7.32e6.91 (m, 5H), 6.44 (s, 2H), 5.06 (d, J¼7.9 Hz, 1H), 4.42 (dd,
J¼18.5, 3.2 Hz, 1H), 4.22 (dd, J¼50.5, 3.1 Hz, 1H), 3.74 (s, 3H), 3.71 (s,
6H), 3.56 (m, 1H). 13C NMR (75 MHz, CDCl3)
d
165.1 (d, J¼261 Hz), 137.6, 130.8, 129.0, 128.7 (2C), 128.5 (2C),
127.4, 92.9 (d, J¼20 Hz), 72.9, 56.0 (d, J¼24 Hz), 17.7. 19F NMR
d
164.8 (d, J¼260 Hz),
(282 MHz, CDCl3)
3030, 2918, 1668, 1452, 1254, 1035. Anal. Calcd for C13H15FO: C,
d
ꢀ100.6 (ddd, J¼50, 23, 18 Hz). IR (cmꢀ1): 3395,
152.9, 137.4, 137.3, 137.1 (2C), 129.1 (2C), 128.7 (2C), 127.7, 103.5 (2C),
92.8 (d, J¼19 Hz), 74.4, 60.8, 57.7 (d, J¼22 Hz), 56.1, 56.0. 19F NMR
75.70; H, 7.33. Found: C, 75.23; H, 77.44. Compound 6e syn: Rf¼0.51
(282 MHz, CDCl3)
d
ꢀ100.8 (ddd, J¼50, 22, 18 Hz). IR (cmꢀ1): 3446,
cyclohexane/EtOAc 8:2. 1H NMR (300 MHz, CDCl3)
d 7.46e7.24 (m,
2943, 1669, 1590, 1454, 1420, 1328, 1233, 1127, 1003. Anal. Calcd for
5H), 5.91e5.75 (m, 1H), 5.63e5.51 (m, 1H), 4.66 (dd, J¼18.1, 3.0 Hz,
1H), 4.58 (t, J¼7.7 Hz, 1H), 4.46 (dd, J¼50.4, 3.0 Hz, 1H), 3.50 (dd,
J¼21.7, 7.8 Hz, 1H), 1.75 (d, J¼6.4 Hz, 3H). 13C NMR (75 MHz, CDCl3)
C
19H21FO4: C, 68.66; H, 6.37. Found: C, 68.77; H, 6.51.
4.3.27. 1-(Benzo[d][1,3]dioxol-5-yl)-3-fluoro-2-phenylbut-3-en-1-ol 6c
(Table 5,entry 3). Following procedure D, 6c was obtained as the pure
anti diastereomer (yellow oil) and the mixture of anti/syn di-
astereomers (yellow oil), after flash chromatography (SiO2, cyclo-
hexane/EtOAc, 95:5 to 70:30). Compound 6c anti: Rf¼0.28
d
165.2 (d, J¼260 Hz), 137.2, 130.9, 129.2, 128.9 (2C), 128.8 (2C),
127.7, 92.6 (d, J¼20 Hz), 72.9, 55.9 (d, J¼23 Hz), 17.8. 19F NMR
(282 MHz, CDCl3)
3033, 1669, 1452, 1251, 1032. Anal. Calcd for C13H15FO: C, 75.70; H,
7.33. Found: C, 75.82; H, 7.44.
d
ꢀ99.7 (ddd, J¼50, 22, 18 Hz). IR (cmꢀ1): 3390,
cyclohexane/EtOAc 8:2. 1H NMR (300 MHz, CDCl3)
d 7.13e6.95 (m,
5H), 6.63 (s, 1H), 6.54e6.37 (m, 2H), 5.78 (d, J¼2.9 Hz, 2H), 4.91 (dd,
J¼9.5, 2.3 Hz, 1H), 4.70 (dd, J¼17.8, 3.0 Hz, 1H), 4.53 (dd, J¼50.1,
3.0 Hz, 1H), 3.58 (dd, J¼25.0, 9.5 Hz, 1H).∙13C NMR (75 MHz, CDCl3)
4.3.30. 5-Fluoro-1,4-diphenylhex-5-en-3-ol
6). Following procedure D, 6f was obtained as the pure anti di-
astereomer (white solid) and the pure syn diastereomer (colorless
6f
(Table
5,entry

G. Lemonnier et al. / Tetrahedron 70 (2014) 3123e3133
3131
oil), after flash chromatography (SiO2, cyclohexane/EtOAc, 95:5 to
70:30). Compound 6f anti: Rf¼0.44 cyclohexane/EtOAc 8:2. 1H NMR
pure anti diastereomer (colorless oil) and the mixture of anti/syn
diastereomers (colorless oil), after flash chromatography (SiO2,
cyclohexane/EtOAc, 95:5 to 70:30). Compound 6i anti: Rf¼0.40
(300 MHz, CDCl3)
d
7.28e6.96 (m, 10H), 4.64 (dd, J¼17.7, 3.0 Hz, 1H),
4.45 (dd, J¼50.2, 3.0 Hz, 1H), 4.09e3.94 (m, 1H), 3.35 (dd, J¼25.4,
cyclohexane/EtOAc 8:2. 1H NMR (300 MHz, CDCl3)
d 7.41e6.96 (m,
8.8 Hz, 1H), 2.84e2.69 (m, 1H), 2.60e2.50 (m, 1H), 1.72e1.46 (m,
9H), 4.87 (ddd, J¼17.7, 2.8, 0.7 Hz, 1H), 4.65 (d, J¼8.7 Hz, 1H), 4.47
(dd, J¼50.5, 2.9 Hz, 1H), 2.85e2.65 (m, 1H), 2.60e2.36 (m, 2H),
1.87e1.64 (m, 1H), 1.50e1.32 (m, 1H).∙13C NMR (75 MHz, CDCl3)
2H). 13C NMR (75 MHz, CDCl3)
d
165.3 (d, J¼262 Hz), 141.7, 137.9 (d,
J¼2 Hz), 128.8, 128.5, 128.4, 128.3, 128.3, 127.5, 125.9, 92.9 (d,
J¼20 Hz), 71.1, 56.4 (d, J¼23 Hz), 36.1, 31.8. 19F NMR (282 MHz,
d
164.3 (d, J¼261 Hz), 141.2, 140.1, 133.8, 128.7 (2C), 128.4 (2C), 128.3
CDCl3)
d
ꢀ101.0 (ddd, J¼50, 25, 18 Hz). IR (cmꢀ1): 3413, 3033, 2910,
(2C), 128.2 (2C), 126.0, 94.7 (d, J¼20 Hz), 73.9, 50.6 (d, J¼24 Hz),
1673, 1493, 1451, 1252, 1080. Anal. Calcd for C18H19FO: C, 79.97; H,
33.0, 28.9. 19F NMR (282 MHz, CDCl3)
d
ꢀ107.6 (ddd, J¼50, 28,
7.08. Found: C, 79.91; H, 7.22. Compound 6f syn: Rf¼0.53 cyclo-
18 Hz). IR (cmꢀ1): 3418, 2954, 1670, 1491, 1253, 1087, 1013. Anal.
Calcd for C18H18ClFO: C, 70.93; H, 5.95. Found: C, 71.15; H, 6.17.
Compound 6i syn: Rf¼0.51 cyclohexane/EtOAc 8:2). 1H NMR
hexane/EtOAc 8:2. 1H NMR (300 MHz, CDCl3)
d 7.30e7.08 (m, 10H),
4.57 (dd, J¼18.2, 3.0 Hz, 1H), 4.33 (dd, J¼50.5, 3.0 Hz, 1H), 4.06 (t,
J¼8.3 Hz, 1H), 3.36 (dd, J¼21.8, 7.6 Hz, 1H), 2.89e2.76 (m, 1H),
2.69e2.59 (m, 1H), 2.02e1.87 (m, 1H), 1.77e1.59 (m, 1H). 13C NMR
(300 MHz, CDCl3)
d
7.43e6.97 (m, 9H), 4.79 (d, J¼6.9 Hz, 1H), 4.62
(dd, J¼18.1, 3.0 Hz, 1H), 4.18 (dd, J¼50.9, 3.0 Hz, 1H), 2.86e2.66 (m,
1H), 2.61e2.38 (m, 2H), 2.16e1.99 (m, 1H), 1.97e1.79 (m, 1H).∙13
NMR (75 MHz, CDCl3)
164.8 (d, J¼259 Hz),141.6,140.7,133.4,128.4
(75 MHz, CDCl3)
d
165.6 (d, J¼260 Hz), 141.9, 137.3, 128.9, 128.9,
C
128.5, 128.4, 127.7, 125.9, 92.5 (d, J¼19 Hz), 70.9, 55.8 (d, J¼23 Hz),
d
36.7, 32.1. 19F NMR (282 MHz, CDCl3)
d
ꢀ100.1 (ddd, J¼50, 22,
(4C), 128.3 (2C), 127.6 (2C), 125.9, 93.5 (d, J¼20 Hz), 74.4, 50.5 (d,
18 Hz). IR (cmꢀ1): 3027, 2926, 1667, 1495, 1453, 1244, 1072. Anal.
Calcd for C18H19FO: C, 79.97; H, 7.08. Found: C, 79.73; H, 7.38.
J¼23 Hz), 33.3, 28.3. 19F NMR (282 MHz, CDCl3)
ꢀ103.5 (ddd, J¼51,
d
26, 18 Hz). IR (cmꢀ1): 3420, 2920, 1671, 1452, 1244, 1125. Anal. Calcd
for C18H18ClFO: C, 70.93; H, 5.95. Found: C, 71.12; H, 6.20.
4.3.31. 2-Fluoro-3-Phenyloct-1-en-4-ol 6g (Table 5,entry 7). Following
procedure D, 6g was obtained as the mixture anti/syn diastereomers
(yellow oil), after flash chromatography (SiO2, cyclohexane/EtOAc,
95:5 to 70:30). Compound 6g anti: Rf¼0.55 cyclohexane/EtOAc 8:2. 1H
4.3.34. (E)-2-Fluoro-3-phenethylhepta-1,5-dien-4-ol 6j (Table 5,en-
try 10). Following procedure D, 6j was obtained as the mixture of
anti/syn diastereomer (colorless oil), after flash chromatography
(SiO2, cyclohexane/EtOAc, 95:5 to 70:30, Rf¼0.43 and 0.47 cyclo-
NMR (300 MHz, CDCl3)
d
7.34e7.13 (m, 5H), 4.64 (dd, J¼17.9, 3.0 Hz,
1H), 4.46 (dd, J¼50.3, 3.0 Hz, 1H), 4.12e3.91 (m, 1H), 3.32 (dd, J¼25.5,
hexane/EtOAc 8:2). 1H NMR (300 MHz, CDCl3)
d 7.27e7.05 (m, 10H),
8.5 Hz, 1H), 1.47e1.06 (m, 6H), 0.75 (t, J¼7.2 Hz, 3H). 13C NMR
5.73e5.54 (m, 2H), 5.49e5.25 (m, 2H), 4.71 (dd, J¼20.8, 2.8 Hz, 1H),
4.65 (dd, J¼21.1, 2.8 Hz, 1H), 4.34 (dd, J¼50.6, 2.8 Hz, 1H), 4.28 (dd,
J¼50.7, 2.8 Hz, 1H), 4.08e3.93 (m, 2H), 2.79e2.59 (m, 2H),
2.58e2.37 (m, 2H), 2.36e2.02 (m, 2H), 1.89e1.60 (m, 10H). 13C NMR
(75 MHz, CDCl3)
d
165.4 (d, J¼262 Hz), 138.2 (d, J¼2 Hz), 129.0, 128.7
(2C), 128.3, 127.4, 92.7 (d, J¼20 Hz), 71.8, 56.3 (d, J¼23 Hz), 34.1, 27.7,
22.5, 14.0. 19F NMR (282 MHz, CDCl3)
d
ꢀ100.7 (ddd, J¼50, 25, 18 Hz).
Compound 6g syn: Rf¼0.60 cyclohexane/EtOAc 8:2. 1H NMR
(75 MHz, CDCl3)
d
165.2 (d, J¼261 Hz), 164.9 (d, J¼261 Hz), 141.8,
(300 MHz, CDCl3)
d
7.34e7.13 (m, 5H), 4.58 (dd, J¼17.9, 2.4 Hz, 1H),
141.7, 131.3, 131.2, 129.8, 128.5 (2C), 128.4 (2C), 128.4 (5C), 126.0,
125.9, 93.8 (d, J¼21 Hz), 93.3 (d, J¼20 Hz), 73.8, 73.3, 49.2 (d,
J¼24 Hz), 48.8 (d, J¼23 Hz), 33.3, 33.3, 29.4, 29.0, 17.8 (2C). 19F NMR
4.38 (dd, J¼50.6, 3.0 Hz, 1H), 4.12e3.91 (m, 1H), 3.34 (dd, J¼21.3,
7.1 Hz, 1H), 1.47e1.06 (m, 6H), 0.81 (t, 7.1 Hz, 3H). 13C NMR (75 MHz,
CDCl3)
d
165.9 (d, J¼260 Hz), 137.5, 129.0, 128.8 (2C), 128.3, 127.6, 92.3
(282 MHz, CDCl3)
d
ꢀ102.2 (ddd, J¼51, 27, 18 Hz), ꢀ105.9 (ddd, J¼51,
(d, J¼20 Hz), 71.5, 55.7 (d, J¼24 Hz), 34.6, 27.9, 22.6, 14.1. 19F NMR
28,18 Hz). IR (cmꢀ1): 3420, 3021, 2932,1668,1452,1250,1001. Anal.
Calcd for C15H19FO: C, 76.89; H, 8.17. Found: C, 76.66; H, 8.13.
(282 MHz, CDCl3)
1494, 1454, 1254. Anal. Calcd for C14H19FO: C, 75.64; H, 8.61. Found: C,
75.42; H, 8.48.
d
ꢀ99.7, ꢀ100.1 (m). IR (cmꢀ1): 2956, 2936, 1668,
4.3.35. 2-Fluoro-3-phenethyloct-1-en-4-ol
6k
(Table
5,entry
11). Following procedure D, 6k was obtained as the mixture of anti/
syn diastereomers (colorless oil), after flash chromatography (SiO2,
cyclohexane/EtOAc, 95:5 to 70:30, Rf¼0.55 cyclohexane/EtOAc 8:2).
4.3.32. 2-Fluoro-3-phenyldodec-1-en-4-ol
6h
(Table
5,entry
8). Following procedure D, 6h was obtained as the pure anti di-
astereomer (colorless oil) and the pure syn diastereomer (colorless
oil), after flash chromatography (SiO2, cyclohexane/EtOAc, 95:5 to
70:30). Compound 6h anti: Rf¼0.58 cyclohexane/EtOAc 8:2. 1H
1H NMR (300 MHz, CDCl3)
d
7.40e7.13 (m, 10H), 4.81 (dd, J¼17.9,
2.4 Hz,1H), 4.76 (dd, J¼18.3, 2.5 Hz,1H), 4.41 (dd, J¼51.1, 2.8 Hz,1H),
4.39 (dd, J¼50.9, 2.8 Hz, 1H), 3.65 (br s, 2H), 2.90e2.72 (m, 2H),
2.70e2.50 (m, 2H), 2.39e2.17 (m, 2H), 2.02e1.76 (m, 4H), 1.72e1.25
NMR (300 MHz, CDCl3)
d
7.37e7.08 (m, 5H), 4.65 (d, J¼17.8 Hz, 1H),
4.47 (d, J¼50.3 Hz, 1H), 4.09e3.90 (m, 1H), 3.32 (dd, J¼25.3, 8.7 Hz,
(m, 12H), 0.93 (t, J¼6.8 Hz, 6H). 13C NMR (75 MHz, CDCl3)
d 165.9 (d,
1H), 1.42e1.06 (m, 14H), 0.79 (t, J¼6.5 Hz, 3H). 13C NMR (75 MHz,
J¼261 Hz), 165.5 (d, J¼261 Hz), 141.9, 141.7, 128.5 (2C), 128.4 (2C),
128.4 (2C), 128.4 (2C), 126.0, 125.9, 93.6 (d, J¼20 Hz), 92.9 (d,
J¼20 Hz), 72.6, 72.0, 48.9 (d, J¼23 Hz), 48.6 (d, J¼23 Hz), 34.4, 34.2,
33.4 (2C), 29.8, 28.7, 28.1, 27.8, 22.7, 22.6, 14.1 (2C). 19F NMR
CDCl3)
d
165.4 (d, J¼261 Hz),138.2,128.7 (2C),128.3 (2C),127.4, 92.7
(d, J¼20 Hz), 71.7, 56.3 (d, J¼23 Hz), 34.4, 31.8, 29.5, 29.4, 29.2, 25.5,
22.6, 14.1. 19F NMR (282 MHz, CDCl3)
d
ꢀ100.8 (ddd, J¼50, 25,
17 Hz). IR (cmꢀ1): 3435, 2917, 2851, 1669, 1466, 1454, 1250, 1081.
Anal. Calcd for C18H27FO: C, 77.65; H, 9.78. Found: C, 77.96; H, 9.88.
Compound 6h syn: Rf¼0.69 cyclohexane/EtOAc 8:2. 1H NMR
(282 MHz, CDCl3)
d
ꢀ101.9 (ddd, J¼51, 28, 18 Hz), ꢀ102.7 (ddd, J¼51,
27, 18 Hz). IR (cmꢀ1): 3450, 2955, 2931, 1667, 1454, 1251, 1001. Anal.
Calcd for C16H23FO: C, 76.76; H, 9.26. Found: C, 76.33; H, 9.19.
(300 MHz, CDCl3)
d
7.37e7.11 (m, 5H), 4.59 (d, J¼18.2 Hz, 1H), 4.39
(d, J¼50.6 Hz, 1H), 4.15e3.93 (m, 1H), 3.34 (dd, J¼21.4, 7.4 Hz, 1H),
4.3.36. 2-(4-Bromophenyl)-1-(4-chlorophenyl)-3-fluorobut-3-en-1-
ol 6l (Table 5, entry 12). Following procedure D, 6l was obtained as
the pure anti diastereomer (colorless oil) and the pure syn di-
astereomer (colorless oil), after flash chromatography (SiO2, cy-
clohexane/EtOAc, 95:5 to 70:30). Compound 6l anti: Rf¼0.43
1.62e1.08 (m, 14H), 0.81 (t, J¼6.0 Hz, 3H). 13C NMR (75 MHz, CDCl3)
d
165.8 (d, J¼260 Hz), 137.4, 129.0 (2C), 128.8 (2C), 127.6, 92.32 (d,
J¼20 Hz), 71.5, 55.7 (d, J¼23 Hz), 34.9, 31.9, 29.6 (2C), 29.3, 25.7,
22.7, 14.1. 19F NMR (282 MHz, CDCl3)
ꢀ100.0 (ddd, J¼50, 21, 18 Hz).
IR (cmꢀ1): 3430, 2923, 2853, 1667, 1463, 1189. Anal. Calcd for
18H27FO: C, 77.65; H, 9.78. Found: C, 77.99; H, 9.66.
d
cyclohexane/EtOAc 8:2. 1H NMR (300 MHz, CDCl3)
d 7.29e7.19 (m,
C
2H), 7.14e7.03 (m, 2H), 7.02e6.90 (m, 2H), 6.90e6.79 (m, 2H), 4.92
(d, J¼9.4 Hz, 1H), 4.73 (dd, J¼17.7, 3.2 Hz, 1H), 4.54 (dd, J¼50.0,
3.2 Hz, 1H), 3.53 (dd, J¼24.7, 9.4 Hz, 1H).∙13C NMR (75 MHz, CDCl3)
4.3.33. 1-(4-Chlorophenyl)-3-fluoro-2-phenethylbut-3-en-1-ol
(Table 5, entry 9). Following procedure D, 6i was obtained as the
6i
d
164.1 (d, J¼262 Hz), 139.4, 136.0 (d, J¼2 Hz), 133.7, 131.6 (2C),

3132
G. Lemonnier et al. / Tetrahedron 70 (2014) 3123e3133
130.2, 130.1, 128.4 (2C), 128.1 (2C), 121.5, 93.7 (d, J¼20 Hz), 74.1 (d,
chromatography (SiO2, cyclohexane/EtOAc, 95:5 to 70:30, Rf¼0.42
cyclohexane/EtOAc 8:2). Compound 6o anti: 1H NMR (300 MHz,
J¼3 Hz), 57.2 (d, J¼24 Hz). 19F NMR (282 MHz, CDCl3)
ꢀ102.3 (ddd,
d
J¼50, 25, 18 Hz). IR (cmꢀ1): 3401, 1670, 1487, 1255, 1088, 1010. Anal.
Calcd for C16H13BrClFO: C, 54.04; H, 3.68. Found: C, 54.32; H, 3.78.
Compound 6l syn: Rf¼0.57 cyclohexane/EtOAc 8:2. 1H NMR
CDCl3)
d
7.40e6.70 (m, 8H), 5.04 (d, J¼9.4 Hz, 1H), 4.80 (dd, J¼17.6,
3.2 Hz, 1H), 4.62 (dd, J¼50.2, 3.1 Hz, 1H), 3.76 (s, 3H), 3.62 (dd,
J¼24.9, 9.5 Hz, 1H).∙13C NMR (75 MHz, CDCl3)
165.0 (d, J¼262 Hz),
d
(300 MHz, CDCl3)
d
7.48e7.36 (m, 2H), 7.28e7.13 (m, 6H), 5.12 (d,
158.8, 139.9, 133.4, 129.5, 129.5, 128.9 (d, J¼2 Hz), 128.2 (2C), 128.1
(2C),113.9 (2C), 93.0 (d, J¼20 Hz), 74.4 (d, J¼3 Hz), 56.8 (d, J¼24 Hz),
J¼7.9 Hz, 1H), 4.44 (dd, J¼18.0, 3.3 Hz, 1H), 4.17 (dd, J¼50.3, 3.2 Hz,
1H), 3.52 (dd, J¼22.5, 7.9 Hz, 1H).∙13C NMR (75 MHz, CDCl3)
d
164.1
55.1. 19F NMR (282 MHz, CDCl3)
d
ꢀ101.9 (ddd, J¼50, 25, 18 Hz).
(d, J¼260 Hz), 139.9, 135.8, 133.8, 131.8 (2C), 130.7, 130.7, 128.5 (2C),
Compound 6o syn: 1H NMR (300 MHz, CDCl3)
d 7.39e6.68 (m, 8H),
127.8 (2C), 121.9, 93.4 (d, J¼19 Hz), 73.6, 57.1 (d, J¼24 Hz). 19F NMR
5.16 (d, J¼8.1 Hz, 1H), 4.48 (dd, J¼18.0, 3.1 Hz, 1H), 4.23 (dd, J¼50.4,
(282 MHz, CDCl3)
1671, 1487, 1249, 1089, 1073, 1011. Anal. Calcd for C16H13BrClFO: C,
54.04; H, 3.68. Found: C, 54.99; H, 4.08.
d
ꢀ101.3 (ddd, J¼50, 22, 18 Hz). IR (cmꢀ1): 3400,
3.1 Hz, 1H), 3.83 (s, 3H), 3.59 (dd, J¼22.7, 9.1 Hz, 1H). 13C NMR
(75 MHz, CDCl3)
d
164.7 (d, J¼260 Hz), 159.3, 140.1, 133.6, 130.0,
129.9, 128.5, 128.4 (2C), 127.9 (2C), 114.3 (2C), 92.8 (d, J¼21 Hz),
73.8, 56.9 (d, J¼24 Hz), 55.2. 19F NMR (282 MHz, CDCl3)
d
ꢀ101.3
4.3.37. (E)-3-(4-Bromophenyl)-2-fluorohepta-1,5-dien-4-ol
6m
(ddd, J¼50, 23, 18 Hz). IR (cmꢀ1): 3463, 2837, 1669, 1610, 1510, 1245,
1177, 1031, 1012. Anal. Calcd for C17H16ClFO2: C, 66.65; H, 5.26.
Found: C, 66.25; H, 5.48.
(Table 5,entry 13). Following procedure D, 6m was obtained as the
pure anti diastereomer (colorless oil) and the pure syn di-
astereomer (colorless oil), after flash chromatography (SiO2, cy-
clohexane/EtOAc, 95:5 to 70:30). Compound 6m anti: Rf¼0.37
Acknowledgements
cyclohexane/EtOAc 8:2. 1H NMR (300 MHz, CDCl3)
d 7.36 (d,
J¼8.5 Hz, 2H), 7.07 (d, J¼8.3 Hz, 2H), 5.65e5.43 (m, 1H), 5.36e5.16
(m, 1H), 4.67 (dd, J¼17.8, 3.1 Hz, 1H), 4.47 (dd, J¼50.2, 3.1 Hz, 1H),
4.40 (t, J¼7.7 Hz, 1H), 3.37 (dd, J¼23.4, 8.5 Hz, 1H), 1.51 (dd, J¼6.5,
This work has been partially supported by INSA Rouen, Rouen
University, CNRS, EFRD, Labex SynOrg (ANR-11-LABX-0029) and
ꢀ
Region Haute-Normandie (CRUNCh network). G.L. and N.V.H. thank
0.9 Hz, 3H). 13C NMR (75 MHz, CDCl3)
d
164.5 (d, J¼261 Hz), 136.7,
the EFRD for a postdoctoral fellowship (EFRD 32819 & EFRD 43209).
131.6 (2C),130.6,130.4 (2C),129.5,121.3, 93.1 (d, J¼20 Hz), 72.7, 55.4
(d, J¼24 Hz), 17.7. 19F NMR (282 MHz, CDCl3)
d
ꢀ101.3 (ddd, J¼50,
References and notes
23, 18 Hz). IR (cmꢀ1): 3396, 2915, 1669, 1487, 1254, 1073, 1010. Anal.
Calcd for C13H14BrFO: C, 54.76; H, 4.95. Found: C, 55.08; H, 5.03.
Compound 6m syn: Rf¼0.52 cyclohexane/EtOAc 8:2. 1H NMR
ꢀ
ꢀ
1. (a) O’Hagan, D. Chem. Soc. Rev. 2008, 37, 308e319; (b) Begue, J.-P.; Bonnet-
Delpon, D. Bioorganic and Medicinal Chemistry of Fluorine; John Wiley & Sons:
Hoboken, NJ, 2008; (c) Kirsch, P. Modern Fluoorganic Chemistry; Wiley-VCH:
Weinheim, Germany, 2004; (d) Mikami, K.; Itoh, Y.; Yamanaka, M. Chem. Rev.
2004, 104, 1e16.
(300 MHz, CDCl3)
d
7.40 (d, J¼8.5 Hz, 2H), 7.18 (d, J¼8.4 Hz, 2H), 5.71
(dq, J¼13.1, 6.4 Hz, 1H), 5.48e5.34 (m, 1H), 4.58 (dd, J¼18.1, 3.1 Hz,
1H), 4.50e4.40 (m, 1H), 4.36 (dd, J¼54.8, 4.5 Hz, 1H), 3.36 (dd,
J¼20.8, 7.5 Hz, 1H), 1.63 (dd, J¼6.5, 1.2 Hz, 3H). 13C NMR (75 MHz,
€
2. (a) Muller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881e1886; (b) Purser, S.;
Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320e330.
3. For review on fluorine introduction see: (a) Furuya, T.; Kuttruff, C. A.; Ritter, T.
Curr. Opin. Drug. Discovery Dev. 2008, 11, 803e819; (b) Furuya, T.; Kamlet, A. S.;
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Angew. Chem., Int. Ed. 2013, 52, 8214e8264; (d) Hollingworth, C.; Gouverneur,
V. Chem. Commun. 2012, 2929e2942.
4. (a) Landelle, G.; Bergeron, M.; Turcotte-Savard, M.-O.; Paquin, J.-F. Chem. Soc.
Rev. 2011, 40, 2867e2908; (b) Yanai, H.; Taguchi, T. Eur. J. Org. Chem. 2011,
5939e5954; (c) Hara, S. Top. Curr. Chem. 2012, 327, 59e86 For selected exam-
ples regarding the fluoroalkenes synthesis, see: (d) Yang, M.-H.; Matikonda, S.
S.; Altman, R. A. Org. Lett. 2013, 15, 3894e3897; (e) Cao, C.-R.; Ou, S.; Jiang, M.;
Liu, J.-T. Org. Biomol. Chem. 2014, 12, 467e473.
CDCl3)
d
164.8 (d, J¼260 Hz), 136.3, 131.7 (2C), 130.8, 130.7 (2C),
129.4, 121.6, 92.9 (d, J¼20 Hz), 72.7, 55.1 (d, J¼24 Hz), 17.7. 19F NMR
(282 MHz, CDCl3)
d
ꢀ100.1 (ddd, J¼50, 21, 18 Hz). IR (cmꢀ1): 3390,
2915, 1669, 1487, 1250, 1074, 1010. Anal. Calcd for C13H14BrFO: C,
54.76; H, 4.95. Found: C, 55.40; H, 3.75.
4.3.38. 3-(4-Bromophenyl)-2-fluorooct-1-en-4-ol 6n (Table 5,entry
14). Following procedure D, 6n was obtained as the pure anti di-
astereomer (colorless oil) and the pure syn diastereomer (colorless
oil), after flash chromatography (SiO2, cyclohexane/EtOAc, 95:5 to
70:30). Compound 6n anti: Rf¼0.42 cyclohexane/EtOAc 8:2. 1H
5. Selected examples: (a) Dutheuil, G.; Couve-Bonnaire, S.; Pannecoucke, X. An-
gew. Chem., Int. Ed. 2007, 46, 1290e1292; (b) Pierry, C.; Couve-Bonnaire, S.;
ꢀ
Guilhaudis, L.; Neveu, C.; Marotte, A.; Lefranc, B.; Cahard, D.; Segalas-Milazzo,
I.; Leprince, J.; Pannecoucke, X. ChemBioChem 2013, 14, 1620e1633; (c) Van der
ꢁ
Veken, P.; Senten, K.; Kertesz, I.; De Meester, I.; Lambeir, A.-M.; Maes, M.-B.;
NMR (300 MHz, CDCl3)
d
7.38 (d, J¼8.5 Hz, 2H), 7.09 (d, J¼8.2 Hz,
ꢀ
Scharpe, S.; Haemers, A.; Augustyns, K. J. Med. Chem. 2005, 48, 1768e1780; (d)
2H), 4.66 (dd, J¼17.7, 3.1 Hz, 1H), 4.46 (dd, J¼50.2, 3.1 Hz, 1H), 3.94
(td, J¼8.2, 3.4 Hz, 1H), 3.29 (dd, J¼25.2, 8.6 Hz, 1H), 1.50e1.02 (m,
Zhao, K.; Lim, D. S.; Funaki, T.; Welch, J. T. Bioorg. Med. Chem. 2003, 11, 207e215
For reviews see: (e) Couve-Bonnaire, S.; Cahard, D.; Pannecoucke, X. Org. Bio-
mol. Chem. 2007, 5, 1151e1157; (f) Taguchi, T.; Yanai, H. In Fluor. Med. Chem.
Chem. Biology; Ojima, I., Ed.; Blackwell: 2009; p 257.
6. (a) Babudri, F.; Farinola, G. M.; Naso, F.; Ragni, R. Chem. Commun. 2007,
1003e1022; (b) Babudri, F.; Cardone, A.; Farinola, G. M.; Martinelli, C.; Men-
dichi, R.; Naso, F.; Striccoli, M. Eur. J. Org. Chem. 2008, 1977e1982.
7. Deng, T.; Shan, S.; Li, Z.-B.; Wu, Z.-W.; Liao, C.-Z.; Ko, B.; Lu, X.-P.; Cheng, J.; Ning,
Z.-Q. Biol. Pharm. Bull. 2005, 28, 1192e1196.
6H), 0.76 (t, J¼7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3)
d 164.8 (d,
J¼262 Hz), 137.3 (d, J¼2 Hz), 131.8 (2C), 130.0, 130.0, 121.4, 93.1 (d,
J¼20 Hz), 71.6, 55.7 (d, J¼24 Hz), 34.2, 27.7, 22.5, 14.0. 19F NMR
(282 MHz, CDCl3)
2937, 1674, 1488, 1244, 1079, 1010. Anal. Calcd for C14H18BrFO: C,
d
ꢀ101.4 (ddd, J¼50, 25, 18 Hz). IR (cmꢀ1): 3346,
55.83; H, 6.02. Found: C, 56.13; H, 6.13. Compound 6n syn: Rf¼0.58
8. Oishi, S.; Kamitani, H.; Kodera, Y.; Watanabe, K.; Kobayashi, K.; Narumi, T.;
Tomita, K.; Ohno, H.; Naito, T.; Kodama, E.; Matsuoka, M.; Fujii, N. Org. Biomol.
Chem. 2009, 7, 2872e2877.
9. Selected examples: (a) Makita, N.; Hoshino, Y.; Yamamoto, H. Angew. Chem., Int.
Ed. 2003, 42, 941e9434; (b) Blanc, A.; Toste, F. D. Angew. Chem., Int. Ed. 2006, 45,
cyclohexane/EtOAc 8:2. 1H NMR (300 MHz, CDCl3)
d 7.41 (d,
J¼8.5 Hz, 2H), 7.18 (d, J¼8.4 Hz, 2H), 4.60 (dd, J¼18.2, 3.1 Hz, 1H),
4.36 (dd, J¼50.5, 3.1 Hz, 1H), 4.02 (td, J¼7.8, 3.2 Hz, 1H), 3.31 (dd,
J¼20.4, 7.0 Hz, 1H), 1.67e1.09 (m, 6H), 0.83 (t, J¼7.1 Hz, 3H). 13C
ꢀ
ꢁ
2096e2099; (c) Malkov, A. V.; Barlog, M.; Miller-Potucka; Kabeshov, L. M. A.;
Farrugia, L. J.; Kocovsky, P. Chem.dEur. J. 2012, 18, 6873e6884.
NMR (75 MHz, CDCl3)
d
165.4 (d, J¼260 Hz), 136.5, 131.8 (2C), 130.8
10. (a) Poisson, T.; Belhomme, M.-C.; Pannecoucke, X. J. Org. Chem. 2012, 77,
9277e9285; (b) Ivashkin, P.; Couve-Bonnaire, S.; Jubault, P.; Pannecoucke, X.
Org. Lett. 2012, 14, 5130e5133; (c) Milanole, G.; Couve-Bonnaire, S.; Bonfanti, J.-
F.; Jubault, P.; Pannecoucke, X. J. Org. Chem. 2013, 78, 212e223; (d) Lemonnier,
G.; Zoute, L.; Quirion, J.-C.; Jubault, P. Org. Lett. 2010, 12, 844e846; (e) Bel-
homme, M.-C.; Poisson, T.; Pannecoucke, X. Org. Lett. 2013, 15, 3428e3431; (f)
David, E.; Milanole, G.; Ivashkin, P.; Couve-Bonnaire, S.; Jubault, P.; Pan-
necoucke, X. Chem.dEur. J. 2012, 18, 14904e14917; (g) Colombel, S.; Van Hijfte,
N.; Poisson, T.; Leclerc, E.; Pannecoucke, X. Chem.dEur. J. 2013, 19,
12778e12787.
(2C), 121.6, 92.7 (d, J¼20 Hz), 71.3, 54.9 (d, J¼24 Hz), 34.7, 27.9, 22.6,
14.0. 19F NMR (282 MHz, CDCl3)
ꢀ100.4 (ddd, J¼50, 20, 18 Hz). IR
(cmꢀ1): 2933, 1669, 1487, 1243, 1073, 1010. Anal. Calcd for
14H18BrFO: C, 55.83; H, 6.02. Found: C, 56.09; H, 5.97.
d
C
4.3.39. 1-(4-Chlorophenyl)-3-fluoro-2-(4-methoxyphenyl)but-3-en-
1-ol 6o (Table 5, entry 15). Following procedure D, 6o was obtained
as the mixture of anti/syn diastereomers (colorless oil), after flash
11. Allmendinger, T.; Angst, C.; Karfunkel, H. J. Fluorine Chem. 1995, 72, 247e253.

G. Lemonnier et al. / Tetrahedron 70 (2014) 3123e3133
3133
12. Hassan, A.; Montgomery, T. P.; Krische, M. J. Chem. Commun. 2012, 4692e4694.
13. Hayashi, T.; Usuki, Y.; Iio, H. J. Fluorine Chem. 2010, 131, 709e713.
14. For reviews dealing with the use of indium (0) in allylation reaction see: (a)
19. For examples of
g
-selectivity with In see: (a) Ranu, B. C.; Samanta, S.; Hajra, A. J.
Org. Chem. 2001, 66, 7519e7521; (b) Cha, J. H.; Pae, A. N.; Choi, K. I. I.; Cho, Y. S.;
Koh, H. Y.; Lee, E. J. Chem. Soc., Perkin Trans. 1 2001, 2079e2081; (c) Cho, Y. S.;
Kang, K. H.; Cha, J. H.; Choi, K. I.; Pae, A. N.; Koh, H. Y.; Chang, M. H. Bull. Korean
Chem. Soc. 2002, 23, 1285e1290; (d) Hirashita, T.; Inoue, S.; Yamamura, H.;
Kawai, M.; Araki, S. J. Organomet. Chem. 1997, 549, 305e309; (e) Woo, S.;
Squires, N.; Fallis, A. G. Org. Lett. 1999, 1, 573e575.
Bowyer, W. J.; Singaram, B.; Sessler, A. M. Tetrahedron 2011, 67, 7449e7460; (b)
ꢀ
Auge, J.; Lubin-Germain, N.; Uziel, J. Synthesis 2007, 1739e1764; (c) Shen, Z.-L.;
Wang, S.-Y.; Chok, Y.-K.; Xu, Y.-H.; Loh, T.-P. Chem. Rev. 2013, 113, 271e401.
15. For a preliminary communication from our group, see: Lemonnier, G.; Poisson,
T.; Couve-Bonnaire, S.; Pannecoucke, X. Tetrahedron Lett. 2013, 54, 2821e2824.
16. For a beneficial effect of brine or saturated aqueous solution in indium pro-
moted allylation reaction see: Sun, X.-W.; Liu, M.; Xu, M.-H.; Lin, G.-Q. Org. Lett.
2008, 10, 1259e1262.
17. So far, we have not been able to determine the stereochemistry of the product.
18. Lemonnier, G.; Zoute, L.; Dupas, G.; Quirion, J.-C.; Jubault, P. J. Org. Chem. 2009,
74, 4124e4131.
20. The X-ray structure has been deposited (anti-6a CCDC 951873) at the Cam-
bridge Crystallographic Data Center.
21. Similar isomerisation have been previously proposed: (a) Paquette, L. A.; Mitzel,
T. M. J. Org. Chem. 1996, 61, 8799e8804; (b) Isaac, M. B.; Chan, T.-H. Tetrahedron
Lett. 1995, 36, 8957e8960; (c) Ho, D. S.-C.; Sim, K.-Y.; Loh, T.-P. Synlett 1996,
263e264.