Microwave assisted fluorofunctionalization of phenyl substituted alkenes using selectfluor

Article abstract of DOI:10.1016/j.jfluchem.2013.02.014

A rapid fluorofunctionalization of alkenes and diene using selectfluor has been uncovered. The olefins such as 1-phenyl ethene; 1,1-diphenylethene; (E)-1,2-diphenylethene; (E)-1,2-dinaphthylethene; 1,1,2-triphenylethene; 1,1,2,2-tetraphenylethene and 1,1,

Full text of DOI:10.1016/j.jfluchem.2013.02.014

Journal of Fluorine Chemistry 150 (2013) 72–77
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Microwave assisted fluorofunctionalization of phenyl substituted alkenes
using selectfluorTM
*
Anil Kumar, Tej Vir Singh , Paloth Venugopalan
Department of Chemistry and Centre of Advanced Studies in Chemistry, Panjab University, Chandigarh 160 014, India
A R T I C L E I N F O
A B S T R A C T
A rapid fluorofunctionalization of alkenes and diene using selectfluorTM has been uncovered. The olefins
such as 1-phenyl ethene; 1,1-diphenylethene; (E)-1,2-diphenylethene; (E)-1,2-dinaphthylethene; 1,1,2-
triphenylethene; 1,1,2,2-tetraphenylethene and 1,1,4-triphenyl-1,3-butadiene react with selectfluorTM
Article history:
Received 4 December 2012
Received in revised form 11 February 2013
Accepted 18 February 2013
Available online 4 March 2013
(F-TEDA-BF4) in water and methanol to give
a-fluorohydrins and a-fluoromethoxy compounds
respectively under microwave radiations. The electrophilic addition of ‘FOH’ and ‘FOMe’ on the double
bond occurs regioselectively with excellent yield.
Keywords:
ß 2013 Elsevier B.V. All rights reserved.
Fluorofunctionalization
Alkenes
Microwave
SelectfluorTM (F-TEDA-BF4)
Fluorohydrins
1. Introduction
selectfluorTM (F-TEDA-BF4) and accufluorTM (NFTh) with phenyl
substituted olefins [12,14,15]. The methodology involves long
The importance of organofluorine compounds is well docu-
mented [1]. There are fast growing demands of fluorinated
building blocks in diverse fields such as medicinal chemistry,
biochemistry and material science [2–4]. Approximately 20% of
drugs in the market contain fluorine and this number is expected to
grow [5]. The presence of fluorine in organic drugs can have a
profound influence on their biological activity by altering the
metabolic stability, hydrogen bonding capability, lipophilicity,
solubility, conformation and overall structure [6]. The ability of
fluorine to have a higher bonding affinity to drug receptors than
non-fluorine containing molecules has made organofluorine
chemistry very important to the pharmaceutical industry [7].
The use of fluorohydrins, in particular vicinal fluorohydrins, is the
subject of recent interest in medicinal chemistry [7c,d]. A precise
methodology is therefore required for their synthesis [8].
reaction time using conventional heating to reflux conditions.
Moreover, in the case of insoluble alkenes, surfactant such as
sodium lauryl ether sulfate has been added to yield good results
[12]. Considering the slow rate of fluorofunctionalization and to
improve the usefulness of this methodology, we resorted to the
use of microwave radiations for the synthesis of
and -fluoromethoxy compounds.
a-fluorohydrins
a
The use of microwaves has played an important role in
organofluorine chemistry [21–29]. As the selectfluorTM (F-TEDA-
BF4) is an electrophilic fluorinating reagent, it would give
electrophilic substitution/addition reactions. The substrates hav-
ing high electron density are suitable for such reactions. The
fluorination of 1-arylethanones [21], 1,3-dicarbonyl compounds
[22], 1-aryl-1-nitromethanes [23] and aromatic compounds [24]
are few examples of electrophilic substitution reactions using
selectfluorTM (F-TEDA-BF4). However, the electrophilic addition
reactions of fluorine are still awaited using selectfluorTM under
microwave radiations. Olefins are considered to be cost effective
and versatile electron rich substrates for such reactions. In this
backdrop, the fluorofunctionalization of olefins using non-con-
ventional microwaves and selectfluor is unprecedent for the
a
-Fluorohydrins have been prepared by reducing a-fluor-
oketones [9], ring opening of epoxide [10] and by fluorofunc-
tionalization of olefins [11–20]. In first two cases, the substrates
are not easily accessible due to the use of some hazardous and
toxic chemicals for their syntheses. The syntheses of
a-
fluorohydrins and derivatives are generally carried out by
the reaction of electrophilic fluorinating reagents such as
synthesis of
Thus, herein we report a rapid synthesis of
a
-fluorohydrins and
a
-fluoromethoxy compounds.
-fluorohydrins and
a
their derivatives by the treatment of phenyl substituted olefins
with selectfluorTM (F-TEDA-BF4) in water and methanol under
microwave radiations.
* Corresponding author. Tel.: +91 172 253 4439.
E-mail address: tvs@pu.ac.in (T.V. Singh).
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.02.014

A. Kumar et al. / Journal of Fluorine Chemistry 150 (2013) 72–77
73
R1
R2
R3
R4
R1
R2
R3
R4
microwave radiations for 2 min (Scheme 1, entry 1). After usual
work up, the product was identified as 2-fluoro-1-phenyletnanol
(2a) on the basis of physical and spectral data [12]. The
regioselectivity of the addition was according to Markownikoff’s
rule [14]. The maximum time period reported for such fluorohy-
droxylation of styrene was 24 h using selectfluorTM (F-TEDA-BF4)
at 60 8C [12] and N-fluorobis[(perfluoroalkyl) sulfonyl] imide at
room temperature [18].
SelectfluorTM (1.1 equiv)
C
C
C
R
C
F
RH, MeCN
MWI, 1-3 min
1a-f
2a-f: R = OH
3a-f: R = OMe
Scheme 1. Fluorofunctionalization of olefins, 1a–f, using selectfluorTM and
After successful fluorohydroxylation of styrene, other olefins
such as 1,1-diphenylethene (1b), (E)-1,2-diphenylethene (1c), (E)-
1,2-dinaphthylethene (1d) 1,1,2-triphenylethene (1e) and 1,1,2,2-
tetraphenylethene (1f), in acetonitrile were irradiated in micro-
wave oven for appropriate time period using above conditions to
microwaves.
2. Results and discussion
In order to obtain phenyl substituted
a
-fluorohydrins, phenyl
give their corresponding a-fluorohydrins (2b–f) (Scheme 1) [12–
substituted olefin such as styrene (1a) in acetonitrile containing
selectfluorTM (F-TEDA-BF4) and water was irradiated under
14,17,18]. Similarly, vicinal fluoromethoxy derivatives (3a–f) of
olefins (1a–f) were obtained by using methanol. The time taken for
Table 1
Reaction time and yield of 2a–f and 3a–f.
Entry
1
Alkene
Product
R
Time (s)
Yielda (%)
H
H
H
H
C
H
H
C
R
C
C
OH
120
120
90
92
F
OMe
1a
2a: R=OH, 3a: R=OMe
2
H
H
H
OH
60
60
98
97
C
R
C
F
C
C
OMe
H
1b
2b: R=OH, 3b: R=OMe
3
H
H
OH
90
60
92b
95b
C
R
C
F
C
C
C
C
OMe
H
H
H
H
1c
2c: R=OH, 3c: R=OMe
4
H
H
OH
120
120
85b
82b
C
R
C
F
C
OMe
H
1d
2d: R=OH, 3d: R=OMe
5
OH
120
90
95
94
C
R
C
F
C
OMe
H
1e
2e: R=OH, 3e: R=OMe
6
OH
180
120
90
90
C
C
C
R
C
F
OMe
1f
2f: R=OH, 3f: R=OMe
a
These are isolated yields of products after flash column chromatography.
b
DL-Threo (1R*, 2S*) and DL-erythro (1R*, 2R*) isomers were formed in these cases and their ratio was estimated by the integration of vicinal protons coupled with each
other in 1H NMR spectra of the mixture.

74
A. Kumar et al. / Journal of Fluorine Chemistry 150 (2013) 72–77
F
F
F
F
C
Ar
Ar
C
H
Ar
Ar
Ar
H
H
H
H
Ar
H
Ar
Or
Or
Ar
H
H
C
C
R
R
R
R
2ct, 2dt, 3ct and 3dt
2ce, 2de, 3ce and 3de
For 2ct and 2ce : Ar = C6H5, R = OH,
For 3ct and 3ce : Ar = C6H5, R = OMe,
For 2dt and 2de: Ar = 1-C10H7, R = OH
For 3dt and 3de: Ar = 1-C10H7, R = OMe
Fig. 1. Sawhorse and Newman projections of (1R*, 2S*) and (1R*, 2R*) isomers of 2c, 2d, 3c and 3d (the italic ‘t’ and ‘e’ denotes threo and erythro isomer).
the reaction and yield of isolated products are given in Table 1.
Markownikoff type of regioselectivity was also observed in case of
fluorofunctionalization of 1b and 1e. The relatively lower yields of
2d, 2f, 3d and 3f were due to the heterogeneity of the reaction
mixture because the alkenes 1d and 1f were partially insoluble in
acetonitrile.
In case of 1c and 1d, diastereomers of vicinal fluorohydrins (2c
and 2d) and fluoromethoxy (3c and 3d) were obtained (Scheme 1).
The formation of DL-erythro (1R*, 2R*) stereoisomer in both cases
was found to be predominant. In 1H NMR, the coupling constant for
vicinal protons is 4.8–5.2 Hz for (1R*, 2R*) isomers while 7.2–
7.5 Hz for (1R*, 2S*) isomers. The presence of two signals as doublet
of doublet at different chemical shift values in 19F NMR further
confirms the presence of two isomers. These two isomers were
separated by flash column chromatography and finally confirmed
by their individual physical and spectral data.
The ratio of two isomers in case of 2c, 2d, 3c and 3d can be
understood from their Sawhorse or Newman projections (Fig. 1).
The two aryl rings are syn to each other in threo (1R*, 2S*) isomer.
The steric hindrance between the two aryl rings decreases the yield
of threo isomer. While the two aryl rings being anti to each other,
increases the yield of more stable erythro 1R*2R* isomer. A little
more yield in case of 1b than 1c reflects the role phenyl group
during fluorofunctionalization. The two phenyl rings present at the
same carbon in 1b stabilizes the carbocation effectively and
thereby increases the yield. Further to study the effect of phenyl
group, a synergistic experiment was carried out. Both 1b and 1c in
equimolar quantity were irradiated together in microwave oven
using one equivalent of selectfluorTM (F-TEDA-BF4) in water for
2 min (Scheme 2). The yields of their corresponding products 2b
and 2c are 48% and 34% respectively. More yield in case of 1b again
suggests a crucial role of the phenyl ring.
4, was chosen. This diene can be considered as having 1,1-
diphenylethene (1b) and (E)-1,2-diphenylethene (1c) moieties.
This will provide a better understanding whether the addition
occurs like that of 1b or 1c alkene. It is further envisaged that the
positive outcome of such reaction would give us an effective
methodology to introduce fluorine in aryl substituted 1,3-dienes.
Keeping this in view (E)-1,1,4-triphenyl-1,3-butadiene (4) was
subjected to fluorohydroxylation using selectfluorTM (F-TEDA-BF4)
and water under microwave radiations for 1 min (Scheme 3). The
organic compound was extracted with DCM, washed with water,
dried over anhydrous Na2SO4 and purified by flash column
chromatography. It was interesting to note that the fluorohydrox-
ylation of 4 occurred according to both 1,2-addition (as in case of
1b) and 3,4-addition (as in case of 1c). By 1,2-addition, 2-fluoro-
1,1,4-triphenyl-but-3-en-1-ol (5) was formed in 35% yield while
(1R*, 2S*)- (7a) and (1R*, 2R*)-1-fluoro-2-hydroxy-1-phenyl-2-
(1,1-diphenylethylenyl) ethane (7b) was obtained by 3,4-addition
reaction in 47% yield [30]. The ratio of 7a and 7b isomer is 33:67. In
this case, both the double bonds of 1,3-diene reacted with the
electrophilic fluorine. The facile electrophilic attack on double
bond occurs in which a relatively more stable a-fluorocarbocation
is formed. The diaryl methyl carbenium ion is formed during 1,2-
addition while allylic carbocation is formed in case of 3,4-addition.
As the allylic carbocations are more stable than diaryl methyl
carbenium ion, the yield of 7a and 7b was more than that of 2-
fluoro-1,1,4-triphenyl-but-3-en-1-ol (5). Similar results were
obtained during the reaction of 4 in methanol to obtain 6, 8a
and 8b. All these compounds were characterized by various
spectral data.
In 1H NMR of 5, C-1 proton appeared as ddd at
d 5.74–5.88. The
large coupling constant value (2JHF = 46.9 Hz) for this proton
suggests that fluorine is present on the carbon bearing hydrogen
atom i.e. C2H. The position of fluorine incorporation into 4 was
further determined by dept-135, HSQC and by consideration of
In order to understand the reactivity pattern of germinal and
vicinal phenyl groups on C55C bond; 1,1,4-triphenyl-1,3-butadiene,
Ph
Ph
H
H
Ph
Ph
H
H
48 %
C
C
F
C
C
C
C
OH
SelectfluorTM (1 equiv)
1b
1c
2b
Ph
H
H
H2O, MeCN
MWI, 2 min
Ph
H
H
34 %
C
C
F
Ph
Ph
OH
2c
Scheme 2. Fluorohydroxylation of equimolar mixture of 1b and 1c.

A. Kumar et al. / Journal of Fluorine Chemistry 150 (2013) 72–77
75
Ph
Ph
H
R
R
R
1
2
SelectfluorTM
(1.1 equiv)
Ph
Ph
H
H
CH=CPh2
Ph
CH=CPh2
H
3
4
H
F
H
Ph
H
RH, MeCN
MWI, 1 min
CH=CHPh
Ph
H
F
F
4
7a. R = OH
7b. R = OH
5. R = OH
8a. R = OMe
8b. R = OMe
6. R = OMe
Scheme 3. Products formed from the fluorofunctionalization of 4, using selectfluor under microwave radiations in the presence of water and methanol.
fluorine couplings in the 1H NMR and 13C NMR spectra. Both the
olefinic protons also appeared as ddd at 6.12–6.20 and at 6.53–
light (
by using 40–63 m
l
= 254 and 355 nm). Flash chromatography was performed
m silica gel (230–400 mesh) and applying
d
d
6.58 respectively. The coupling constant value for the olefinic
nitrogen pressure from the top of the column.
protons (3JHH = 16 Hz) suggested that these protons were trans to
each other. The double doublet at
for carbon bearing fluorine at
d
À9.9 in 19F NMR and a doublet
4.2. General procedure for the fluorofunctionalization of olefins (1a–f)
d
95.0 (1JCF = 176 Hz) in 13C NMR
further supported the structure formula assigned to 5. Beside this,
the presence of two isomers (7a and 7b) was confirmed by 1H NMR
spectral data. In this case, the yield of (1R*, 2R*) isomer (7b) was
found to be more than that of (1R*, 2S*) isomer (7a). The coupling
constant value for (1R*, 2S*) isomer is 6.6 Hz while it is 4.2 Hz for
the (1R*, 2R*) isomer. Similar observations were recorded for 6, 8a
and 8b.
A solution of phenyl substituted olefin, 1a–f (100 mg, 0.10–
0.30 mmol) in acetonitrile (10 mL), F-TEDA-BF4 (0.11–0.33 mmol,
1.1 equiv.) and water (2 mL) or methanol (2 mL) was taken in a
100 mL erlenmeyer flask. The mixture was irradiated under
microwave oven for 1–3 min. After cooling to room temperature
the crude product was extracted with DCM. The insoluble material
was filtered off. The filtrate was washed with water and dried over
anhydrous Na2SO4. The solvent wasremovedunder reduced pressure
to give product 2a–f and 3a–f. The structure formulae for compounds
2a–f and 3a–f have been supported by the spectral data.
3. Conclusion
A convenient and rapid method for the preparation of
a-
fluorohydrins and -fluoromethoxy compounds of phenyl substi-
a
4.2.1. 2-Fluoro-1-phenylethanol [12] (2a)
tuted alkenes and diene has been developed. The electrophilic
addition of ‘FOH’ and ‘FOMe’ on alkene and diene has been
accomplished using selectfluorTM (F-TEDA-BF4) in water and
methanol under microwave radiations. The excellent regioselec-
tivity of the addition reaction in case of 1a, 1b and 1e suggests the
formation of a stable carbenium ion as an intermediate in
fluorofunctionalization.
Colourlessoil. 1HNMR(CDCl3, 300 MHz):
d
2.86(s, 1H,OH), 4.53–
2
3
4.71 (dm, 2H, JHF = 47.1 Hz), 5.15–5.27 (ddd, 1H, JHF = 14.1 Hz,
3JHH = 8.2 Hz, 3JHH = 3.9 Hz), 7.08–7.30 (m, 5H, ArH). 19F NMR (CDCl3,
282 MHz):
d
À60.4 (td, 2JFH = 47.1 Hz, 3JFH = 14.1 Hz).
4.2.2. 2-Fluoro-1,1-diphenylethanol (2b)
White solid. Mp 63–64 8C (Lit. [12] mp 65–66.7 8C). 1H NMR
2
(CDCl3, 300 MHz):
d
2.89 (s, 1H, OH), 4.69 (d, 2H, JHF = 47.7 Hz),
4. Experimental
7.14–7.35 (m, 10H, ArH). 13C NMR (CDCl3, 75 MHz):
d
77.7 (d,
2JCF = 18.5 Hz, C-1), 86.2 (d, JCF = 178.6 Hz, C-2), 126.7, 127.7,
128.3, 142.4. 19F NMR (CDCl3, 282 MHz):
1
4.1. Equipments/chemicals
d
À50.9 (t, 2JFH = 47.7 Hz).
Microwave oven (BPL, BMC-900T) operated at 1350 W having
radiations of 2450 MHz frequency. The IR spectra were recorded on
Perkin Elmer IR 1800 spectrophotometer. The 1H NMR and 13C
NMR spectra were recorded in CDCl3 on JEOL AL 300 spectrometer
operating at 300 MHz and 75 MHz respectively with TMS as an
internal standard. 19F NMR spectra were measured on JEOL AL 300
spectrometer operating at 282 MHz. For 1H NMR and 13C NMR
spectra, chemical shifts are in parts per million relative to TMS
while for 19F NMR spectra, the chemical shift values are relative to
4.2.3. A mixture of (1R*, 2S*) and (1R*, 2R*)-1-Fluoro-2-hydroxy-1,2-
diphenylethane, 2c [12,20] (separated by flash chromatography, yield
92%, ratio 35:65)
(1R*, 2S*)-1-Fluoro-2-hydroxy-1,2-diphenylethane (2ct).
White solid. Mp 96–98 8C (Lit. [20] mp 99 8C). 1H NMR (CDCl3,
300 MHz): d
2.8 (s, 1H, OH), 4.93 (dd, 1H, 3JHF = 12.7, 3JHH = 7.5 Hz),
5.39 (dd, 1H, 2JHF = 47.6 Hz, 3JHH = 7.5 Hz), 7.10–7.28 (m, 10H, ArH).
2
19F NMR (CDCl3, 282 MHz):
3JFH = 12.7 Hz).
d
À13.1 (dd, JFH = 47.6 Hz,
hexafluorobenzene which has chemical shift value at
d
(1R*, 2R*)-1-Fluoro-2-hydroxy-1,2-diphenylethane (2ce).
White solid. Mp 98–99 8C (Lit. [20] mp 99 8C). 1H NMR (CDCl3,
À164.9 ppm relative to CFCl3. Coupling constants are in hertz
(Hz). The 1H NMR and 13C NMR spectra of 5, 6, 8a and 8b were
recorded in CDCl3 on Bruker Avance 400 spectrometer operating at
400 MHz and 100 MHz respectively with TMS as an internal
standard. Alkene 1a, 1,3-diene, 4 and selectfluorTM (F-TEDA-BF4)
were purchased from Sigma–Aldrich. A toluene solution of 1,1-
diphenylethanol was heated under reflux in the presence of a
catalytic amount of PTSA to obtain alkene 1b. Similarly, alkene 1e
was prepared from 1,1,2-triphenylethanol. Alkenes 1c and 1d were
synthesized by McMurry coupling reaction [31]. Alkene 1f was
prepared from dichlorodiphenyl methane [32]. TLC analyses were
performed using aluminium backed plates pre-coated with silica
gel containing fluorescent material and examining them under UV
300 MHz): d
2.0 (s, 1H, OH), 4.91 (dd, 1H, 3JHF = 12.3, 3JHH = 5.5 Hz),
5.36 (dd, 1H, 2JHF = 45.8 Hz, 3JHH = 5.5 Hz), 7.13–7.27 (m, 10H, ArH).
2
19F NMR (CDCl3, 282 MHz):
3JFH = 12.2 Hz).
d
À15.5 (dd, JFH = 45.8 Hz,
4.2.4. A mixture of (1R*, 2S*) and (1R*, 2R*)-1-Fluoro-2-hydroxy-1,2-
dinaphthylethane, (2d)
Viscous oil. Yield 85%. Ratio 33:67. FT-IR (neat): 3417, 3051,
2977, 2903, 1597, 1513, 1384, 1247.
(1R*, 2S*)-1-Fluoro-2-hydroxy-1,2-dinaphthylethane (2dt).
1H NMR (CDCl3, 300 MHz):
d
2.0 (s, 1H, OH), 5.95 (dd, 1H,
3JHF = 14.4, 3JHH = 6.3 Hz), 6.42 (dd, 1H, 2JHF = 46.8 Hz,

76
A. Kumar et al. / Journal of Fluorine Chemistry 150 (2013) 72–77
3JHH = 6.3 Hz), 7.19–7.54 (m, 14H, ArH). 19F NMR (CDCl3,
(1R*, 2S*)-1-Fluoro-2-methoxy-1,2-dinaphthylethane (3de).
White solid. Mp 107–108 8C. 1H NMR (CDCl3, 300 MHz):
3.16 (s,
2
3
282 MHz):
d
À15.2 (dd, JFH = 47.1 Hz, JFH = 13.8 Hz).
d
3
3
(1R*, 2R*)-1-Fluoro-2-hydroxy-1,2-dinaphthylethane (2de).
3H, OCH3), 5.38 (dd, 1H, JHF = 15.0 Hz, JHH = 4.8 Hz, C1–H), 6.46
(dd, 1H, 2JHF = 45.6 Hz, 3JHH = 4.8 Hz, C2H), 7.21–7.38 (m, 8H, ArH),
1H NMR (CDCl3, 300 MHz):
d 2.8 (s, 1H, OH), 6.08 (dd, 1H,
3JHF = 12.3, 3JHH = 5.4 Hz), 6.54 (dd, 1H, 2JHF = 45.3 Hz,
3JHH = 5.4 Hz), 7.64–7.86 (m, 14H, ArH). 19F NMR (CDCl3,
7.64–7.85 (m, 6H, ArH). 13C NMR (CDCl3, 75.53 MHz):
d 57.3, 82.9
2
1
(d, JCF = 24.9 Hz, C-1), 92.7 (d, JCF = 178.7 Hz, C-1), 122.9 (d),
123.5, 124.5, 124.9, 125.1, 125.3, 125.4, 125.5, 125.8, 126.1, 126.5,
128.7, 130.6, 132.1 (d), 132.5, 133.3 (d). 19F NMR (CDCl3,
2
3
282 MHz):
d
À14.1 (dd, JFH = 45.7 Hz, JFH = 12.1 Hz).
4.2.5. 2-Fluoro-1,1,2-triphenylethanol (2e)
282 MHz):
d
À15.5 (dd, 2JFH = 45.9 Hz, 3JFH = 15.1 Hz). Anal. Calcd.
White solid. Mp 153–154 8C (Lit. [18] mp 153–155 8C). 1H NMR
for C23H19FO: C, 83.61; H, 5.80. Found: C, 83.66; H, 5.84.
(CDCl3, 300 MHz): d
2.7 (s, 1H, OH), 6.2 (d, 1H, 2JHF = 44.9 Hz), 6.89–
6.92 (m, 2H, ArH), 7.10–7.13 (m, 8H, ArH), 7.22–7.32 (m, 3H, ArH),
4.2.11. 1-Fluoro-2-methoxy-1,1,2-triphenylethane (3e)
7.47–7.50 (m, 2H, ArH). 13C NMR (CDCl3, 75 MHz):
d
77.5 (d,
White solid. Mp 60–61 8C (Lit. [16] mp 61–62 8C). 1H NMR
1
5
2JCF = 22.8 Hz, C-1), 94.6 (d, JCF = 181.7 Hz, C-2), 126.5, 127.3,
(CDCl3, 300 MHz):
d
3.16 (d, 3H, JHF = 1.2 Hz OCH3), 6.16 (d, 1H,
127.5, 127.8, 128.1, 128.7, 139.0, 141.7. 19F NMR (CDCl3, 282 MHz):
2JHF = 44.7 Hz), 6.73–6.75 (m, 2H, ArH), 6.99–7.09 (m, 3H, ArH),
2
d
À12.4 (d, JFH = 44.9 Hz).
7.14–7.17 (m, 10H, ArH). 13C NMR (CDCl3, 75 MHz):
d 53.1 (d,
4JCF = 3.6 Hz) 84.6 (d, 2JCF = 22.8 Hz, C-1), 94.5 (d, 1JCF = 184.2 Hz, C-
4.2.6. 2-Fluoro-1,1,2,2-tetraphenylethanol (2f)
2), 124.4, 127.5, 127.9, 128.8, 129.3, 136.0, 140.0, 141.4. 19F NMR
Whitesolid. Mp180–181 8C (Lit.[18]mp180 8C). 1H NMR (CDCl3,
(CDCl3, 282 MHz):
d
À12.5 (d, JFH = 44.7 Hz).
2
300 MHz): d 2.86 (s, 1H, OH), 7.02–7.11 (m, 12H, ArH), 7.18–7.2 (m,
2
8H, ArH). 13C NMR (CDCl3, 75 MHz):
d
81.5 (d, JCF = 26 Hz, C-1),
4.2.12. 1-Fluoro-2-methoxy-1,1,2,2-tetraphenylethane (3f)
1
100.4 (d, JCF = 186.0 Hz, C-2), 126.8, 127.2, 127.5, 127.9, 128.0,
White solid. Mp 150–151 8C (Lit. [16] mp 152.9–153.5 8C). 1H
128.1, 140.9, 143.5. 19F NMR (CDCl3, 282 MHz):
d
25.3 (s).
NMR (CDCl3, 300 MHz):
d
3.16 (d, 3H, JHF = 1.1 Hz OCH3),7.04–
5
7.44 (m, 20H, ArH). 13C NMR (CDCl3, 75 MHz):
d 53.1 (d,
2
1
4.2.7. 1-Fluoro-2-methoxy-1-phenylethane[15] (3a)
4JCF = 1.8 Hz), 90.1 (d, JCF = 30.3 Hz, C-1), 99.0 (d, JCF = 184.2 Hz,
Colourless oil. 1H NMR (CDCl3, 300 MHz):
d
3.29 (s, 3H, OCH3),
C-2), 126.6, 126.7, 126.9, 127.1, 127.3, 131.1, 138.8, 143.2. 19F NMR
4.50–4.68 (dm, 2H, 2JHF = 46.8 Hz), 5.12–5.26 (ddd, 1H, 3JHF = 14.4 Hz,
3JHH = 8.1 Hz, 3JHH = 4.2 Hz), 7.18–7.28 (m, 5H, ArH). 19F NMR (CDCl3,
(CDCl3, 282 MHz): d 15.7 (s).
282 MHz):
d
À59.6 (td, 2JFH = 46.8 Hz, 3JFH = 14.4 Hz).
4.3. General procedure for the fluorofunctionalization of (E)-1,1,4-
triphenyl-1,3-butadiene (4)
4.2.8. 1-Fluoro-2-methoxy-1,1-diphenylethane[15] (3b)
Colourless oil. 1H NMR (CDCl3, 300 MHz):
d
3.21 (d, 3H,
A solution 1,3-diene, 4 (100 mg, 0.35 mmol) in acetonitrile
(10 mL), F-TEDA-BF4 (1.1 equiv) and water (2 mL) or methanol
(2 mL) was taken in a 100 mL erlenmeyer flask. The mixture was
irradiated under microwave radiations for 1 min. After cooling to
room temperature the crude product was extracted with DCM. The
insoluble material was filtered off. The filtrate was washed with
water and dried over anhydrous Na2SO4. The solvent was removed
under reduced pressure to give the yellowish oil product, which
was purified by flash column chromatography to yield 5, 6, 7a + 7b
and 8a + 8b.
5JHF = 1.2 Hz, OCH3), 4.80 (d, 2H, 2JHF = 47.7 Hz), 7.13–7.27 (m, 10H,
4
ArH). 13C NMR (CDCl3, 75 MHz):
d
52.6 (d, JCF = 3.7 Hz), 82.3 (d,
2JCF = 16.7 Hz, C-1), 85.5 (d, JCF = 182.3 Hz, C-2), 127.7, 127.8,
1
128.2, 141.3. 19F NMR (CDCl3, 282 MHz):
d
À51.5 (t, 2JFH = 47.7 Hz).
4.2.9. A mixture of (1R*, 2S*) and (1R*, 2R*)-1-Fluoro-2-methoxy-1,2-
diphenylethane, 3c [13,19] (separated by flash chromatography, yield
95%, ratio 33:67)
(1R*, 2S*)-1-Fluoro-2-methoxy-1,2-diphenylethane (3ct).
Colourless oil. 1H NMR (CDCl3, 300 MHz):
d 3.26 (s, 3H, OCH3),
3
3
4.36–4.42 (dd, 1H, JHF = 12.9, JHH = 7.2 Hz), 5.31–5.49 (dd, 1H,
4.3.1. 2-Fluoro-1,1,4-triphenyl-but-3-en-1-ol (5)
Yield 35%. White solid. Mp 118–119 8C. IR (KBr): 3569, 3058,
3024, 1597, 1493, 1447, 1174, 1064, 1033, 966, 748, 699 cmÀ1. 1H
3
2JHF = 47.1 Hz, JHH = 7.2 Hz), 7.04–7.25 (m, 10H, ArH). 19F NMR
2
3
(CDCl3, 282 MHz):
d
À12.5 (dd, JFH = 47.1 Hz, JFH = 12.9 Hz).
(1R*, 2R*)-1-Fluoro-2-methoxy-1,2-diphenylethane (3ce).
White solid. Mp 50–51 8C (Lit. [19] mp 51–52 8C). 1H NMR (CDCl3,
NMR (CDCl3, 400 MHz): d 2.76 (d, 1H, 3 JHH = 1.7 Hz, OH), 5.74–
2
3
4
5.88 (ddd, 1H, JHF = 46.9 Hz, JHH = 6.8 Hz, JHH = 1.0 Hz, C2H),
6.12–6.20 (ddd, 1H, 3JHH = 16 Hz, 3JHF = 12.5 Hz, 3JHH = 6.8 Hz, C3H),
6.53–6.58 (ddd, 1H, 3JHH = 16 Hz, 4JHF = 3.9 Hz, 3JHH = 1.0 Hz, C4H),
7.13–7.24 (m, 9H, ArH), 7.28–7.36 (m, 4H, ArH), 7.51–7.54 (m, 2H,
3
300 MHz):
d
3.17 (s, 3H, OCH3), 4.33–4.39 (dd, 1H, JHF = 14.1,
2
3
3JHH = 5.4 Hz), 5.36–5.53 (dd, 1H, JHF = 45.9 Hz, JHH = 5.4 Hz),
7.12–7.31 (m, 10H, ArH). 19F NMR (CDCl3, 282 MHz):
2JFH = 45.9 Hz, JFH = 14.1 Hz).
d
À16.4 (dd,
3
ArH). 13C NMR (CDCl3, 100 MHz):
d
79.2 (d, 2JCF = 22.1 Hz, C-1), 95.0
1
2
(d, JCF = 177.6 Hz, C-2), 122.6 (d, JCF = 18.2 Hz, C-3), 126.3, 126.8
4.2.10. A mixture of (1R*, 2S*) and (1R*, 2R*)-1-Fluoro-2-methoxy-
1,2-dinaphthylethane, 3d (separated by flash chromatography, yield
82%, ratio 30:70)
(d), 127.4 (d), 128.2, 128.3, 135.8 (d, 3JCF = 12.4 Hz, C-4), 142.6 (d),
143.9. 19F NMR (CDCl3, 282 MHz):
d
À9.9 (dd, JFH = 45.6 Hz,
2
3JFH = 12.2 Hz). Anal. Calcd. for C22H19FO: C, 82.99; H, 6.02. Found:
(1R*, 2S*)-1-Fluoro-2-methoxy-1,2-dinaphthylethane (3dt).
C, 83.02; H, 5.98.
Colourless oil. 1H NMR (CDCl3, 300 MHz):
d 3.30 (s, 3H, OCH3), 5.41
3
3
(dd, 1H, JHF = 13.2 Hz, JHH = 7.2 Hz, C1–H), 6.36 (dd, 1H,
4.3.2. A mixture of (1R*, 2S*) and (1R*, 2R*)-1-Fluoro-2-hydroxy-1-
phenyl-2-(1,1-diphenylethylenyl) ethane (light yellowish oil, yield
47%, ratio 33:67)
2JHF = 46.8 Hz, JHH = 7.2 Hz, C2H), 7.14–7.30 (m, 8H, ArH), 7.52–
3
7.63 (m, 4H, ArH), 7.65 (d, 1H, J = 8.7 Hz, ArH), 7.99 (d, 1H,
J = 8.4 Hz, ArH). 13C NMR (CDCl3, 75.53 MHz):
d
57.3, 84.3 (d,
(1R*,
2S*)-1-Fluoro-2-hydroxy-1-phenyl-2-(1,1-dipheny-
2JCF = 24.9 Hz, C–O), 94.0 (d, 1JCF = 182.4 Hz, C–F), 123.3, 124.5 (d),
125.3, 125.5, 125.6, 125.7, 125.8 (d), 126.5, 126.8, 128.5 (d), 128.8,
129.0, 130.4 (d), 131.6, 132.2 (d), 132.4, 133.3 (d). 19F NMR (CDCl3,
lethylenyl) ethane (7a). 1H NMR (CDCl3, 300 MHz):
d
2.27 (s,
2
1H, OH), 4.36 (m 1H, C2H), 5.22 (dd, 1H, JHF = 47.1 Hz,
3JHH = 6.6 Hz, C1H), 5.91 (d, 1H, JHH = 9.9 Hz, C3H), 6.71–7.29 (m,
3
2
3
282 MHz):
d
À12.1 (dd, JFH = 47.1 Hz, JFH = 13.7 Hz). Anal. calcd.
15H, ArH). 19F NMR (CDCl3, 282 MHz):
d
À27.1 (dd, 2JFH = 47.1 Hz,
for C23H19FO: C, 83.61; H, 5.80. Found: C, 83.64; H, 5.79.
3JFH = 13.5 Hz).

A. Kumar et al. / Journal of Fluorine Chemistry 150 (2013) 72–77
[2] (a) J.P. Begue, D. Bonnet-Delpon, J. Fluorine Chem. 127 (2006) 992–1001;
77
(1R*,
2R*)-1-Fluoro-2-hydroxy-1-phenyl-2-(1,1-dipheny-
(b) K.L. Kirk, J. Fluorine Chem. 127 (2006) 1013–1029.
[3] P. Kirch, M. Bremer, Angew. Chem. Int. Ed. 39 (2000) 4216–4235.
[4] M. Shionizv, T. Hiyaona, Angew. Chem. Int. Ed. 44 (2005) 214–231.
[5] (a) A.M. Thayer, Chem. Eng. News 84 (2006) 15–24;
(b) A.M. Thayer, Chem. Eng. News 84 (2006) 27–32.
lethylenyl) ethane (7b). 1H NMR (CDCl3, 300 MHz):
d 1.88 (d,
4
1H, JHH = 1.4 Hz, OH), 4.32 (m 1H, C2H), 5.34 (dd, 1H,
3
3
2JHF = 46.8 Hz, JHH = 4.2 Hz, C1H), 5.99 (d, 1H, JHH = 9.9 Hz, C3H),
6.84–7.29 (m, 15H, ArH). 19F NMR (CDCl3, 282 MHz):
d
À22.2 (dd,
[6] W.G. Dauben, Organic Reactions, vol. 28, John Wily & Sons, New York, 1982, pp.
203–331 (and references there in).
2JFH = 46.8 Hz, JFH = 16.9 Hz).
3
[7] (a) R. Gree, Ind. J. Chem. 39B (2000) 646–673;
(b) S.D. Rychnovsky, G. Yang, J.P. Piwers, J. Org. Chem. 58 (1993) 5251–5255;
(c) A.G. Myers, J.K. Barbay, B. Zheng, J. Am. Chem. Soc. 123 (2001) 7207–7219;
(d) J.T. Welch, S. Eswarakrishnan (Eds.), Fluorine in Bioorganic Chemistry, Wiley,
New York, NY, 1991.
4.3.3. 3-Fluoro-4-methoxy-1,4,4-triphenylbut-1-ene (6)
Yield 34%. Light yellowish oil. IR (KBr): 3057, 3028, 1591, 1497,
1444, 1176, 1067, 1033 cmÀ1. 1H NMR (CDCl3, 400 MHz):
3.17 (d,
d
5
2
[8] For review on syntheses of a-fluorohydrins, see G. Haufe, J. Fluorine Chem. 125
(2004) 875–894.
[9] (a) P.V. Ramachandran, A.V. Teoderoviae, B. Gong, H.C. Brown, Tetrahedron:
Asymm. 5 (1994) 1075–1086;
3H, JHH = 1.8 Hz, OCH3), 5.74–5.88 (ddd, 1H, JHF = 47.2 Hz,
3JHH = 6.6 Hz, 4JHH = 0.9 Hz, C3H), 6.04–6.13 (ddd, 1H, 3JHH = 16 Hz,
3JHF = 12.2 Hz, 3JHH = 6.6 Hz, C2H), 6.43–6.48 (ddd, 1H, 3JHH = 16 Hz,
4JHF = 3.8 Hz, 3JHH = 0.9 Hz, C1H), 7.13–7.16 (m, 3H, ArH), 7.17–7.26
(b) E. Fuglseth, E. Sundby, P. Bruhiem, B.H. Hoff, Tetrahedron: Asymm. 19 (2008)
1941–1946;
(c) D.K. Jones, D.C. Liotta, I. Shinkai, D.J. Mathre, J. Org. Chem. 58 (1993) 799–
801;
(d) T.H.K. Thvedt, E. Fuglseth, E. Sundby, B.H. Hoff, Tetrahedron 66 (2010)
6733–6743;
(e) E. Fuglseth, E. Sundby, P. Bruhiem, B.H. Hoff, J. Fluorine Chem. 130 (2009)
600–603;
(f) M. Reetz, Angew. Chem. Int. Ed. 23 (1984) 556–569 (and reference cited
there in);
(g) P.K. Mohanta, T.A. Davis, J.R. Gooch, R.A. Flowers, J. Am. Chem. Soc. 127
(2005) 11896–11897.
(m, 12H, ArH). 13C NMR (CDCl3, 100 MHz):
d
55.8 (d, JCF = 4 Hz,
4
OCH3), 84.2 (d, 2JCF = 21 Hz, C-4), 95.3 (d, 1JCF = 181 Hz, C-3), 123.4
2
(d, JCF = 17 Hz, C-2), 126.7 (d), 127.4, 127.5, 127.8, 127.9, 128.1,
128.5, 128.7 (d) 134.7 (d, 3JCF = 12 Hz, C-1), 136.3 (d), 140.6, 141.5
(d). 19F NMR (CDCl3, 282 MHz):
d
À8.03 (dd, JFH = 47.1 Hz,
2
3JFH = 12.1 Hz). Anal. calcd. for C23H21FO: C, 83.10; H, 6.37. Found:
C, 83.11; H, 6.36.
[10] (a) A.J. Cresswell, S.G. Davies, J.A. Lee, P.M. Roberts, A.J. Russell, J.E. Thompson,
M.J. Tyte, Org. Lett. 12 (2010) 2936–2939;
4.3.4. A mixture of (1R*, 2S*) and (1R*, 2R*)-1-Fluoro-2-methoxy-1-
phenyl-2-(1,1-diphenylethylenyl) ethane (A light yellowish oil, yield
47%, ratio 35:65)
(b) T. Inagabi, T. Fubuhara, S. Hara, Synthesis (2003) 1157–1159;
(c) G. Haufe, S. Bruns, Adv. Synth. Catal. 344 (2002) 165–171;
(d) G. Haufe, S. Bruns, M. Runge, J. Fluorine Chem. 112 (2001) 55–61;
(e) N. Yoned, Tetrahedron 47 (1991) 5329–5365.
(1R*,
2S*)-1-fluoro-2-methoxy-1-phenyl-2-(1,1-dipheny-
3.24 (s,
lethylenyl) ethane (8a). 1H NMR (CDCl3, 400 MHz):
d
[11] J. Pavlinac, M. Zupan, S. Stavber, Molecules 14 (2009) 2394–2409.
[12] G. Stavber, M. Zupan, M. Jereb, S. Stavber, Org. Lett. 26 (2004) 4973–4976.
[13] S. Stavber, T. Sotler-Pecan, M. Zupan, Bull. Chem. Soc. Jpn. 69 (1996) 169–175.
[14] S. Stavber, M. Zupan, A.J. Pss, G.A. Shia, Tetrahedron Lett. 36 (1995) 6769–
6772.
[15] S. Stavber, T. Sotler-Pecan, M. Zupan, Tetrahedron Lett. 35 (1994) 1105–1108.
[16] M. Zupan, M. Metelko, S. Stavber, J. Chem. Soc. Perkin Trans. 1 (1993) 2851–
2855.
3H, OCH3), 3.96 (ddd, 1H, 3JHF = 16.6 Hz, 3JHH = 9.8 Hz,
3JHH = 6.6 Hz, C3H), 5.37 (dd, 1H, 2JHF = 46.7 Hz, 3JHH = 6.6 Hz, C4H),
5.82 (d, 1H, 3JHH = 9.8 Hz, C2H), 7.04–7.08 (m, 2H, ArH), 7.23–7.44
(m, 13H, ArH). 19F NMR (CDCl3, 282 MHz):
2JFH = 47.1 Hz, JFH = 13.5 Hz).
d
À27.1 (dd,
3
(1R*,
2R*)-1-fluoro-2-methoxy-1-phenyl-2-(1,1-dipheny-
3.16 (s,
[17] G.S. Lal, J. Org. Chem. 58 (1993) 2791–2796.
lethylenyl) ethane (8b). 1H NMR (CDCl3, 400 MHz):
d
[18] D.D. Desmarteu, Z.-Q. Xu, M. Witz, J. Org. Chem. 57 (1992) 629–635.
[19] S. Stavber, M. Zupan, J. Org. Chem. 52 (1987) 919–921.
[20] S. Rozen, O. Lerman, J. Org. Chem. 45 (1980) 672–678.
[21] T.H.K. Thvedt, E. Fuglseth, E. Sunby, B.H. Hoff, Tetrahedron 65 (2009) 9550–9556.
[22] I.C. Xiao, J.M. Shreeve, J. Fluorine Chem. 126 (2005) 475–478.
[23] H. Loghmani-Khouzani, M.M. Sadeghi, R. Ranjbar-Karimi, J. Iran. Chem. Soc. 2
(2005) 330–333.
[24] G.W. Bluck, N.B. Carter, S.C. Smith, M.D. Turnbull, J. Fluorine Chem. 125 (2004)
1873–1877.
[25] H.P. Le, C.E. Mueller, Bioorg. Med. Chem. Lett. 16 (2006) 6139–6142.
[26] S. Marque, H. Snoussi, A. Loupy, N. Ple, A. Turck, J. Fluorine Chem. 125 (2004)
1847–1851.
[27] B. Malo-Forest, J.-A. Roy, J.-F. Paquin, J. Fluorine Chem. 145 (2012) 73–80.
[28] H.G. Bonacorso, J. Navarini, C.W. Wiethan, A.F. Junges, S. Cavinatto, R. Andrighetto,
M.A.P. Martins, N. Zanatta, J. Fluorine Chem. 142 (2012) 90–95.
[29] B.L. Li, D.-Q. Xu, A.G. Zhong, J. Fluorine Chem. 144 (2012) 45–50.
[30] These names of 7a, 7b, 8a and 8b follow DL-threo (1R*, 2S*) and DL-erythro (1R*,
2R*) pattern. However, the names 4-fluoro-1,4,4-triphenylbut-3-en-2-ol (7a, 7b)
and 4-fluoro-3-methoxy-1,1,4-triphenylbut-1-ene (8a and 8b) are according to
IUPAC nomenclature.
3H, OCH3), 3.86 (ddd, 1H, 3JHF = 18.4 Hz, 3JHH = 9.8 Hz,
3JHH = 3.9 Hz, C3H), 5.48 (dd, 1H, 2JHF = 46.8 Hz, 3JHH = 3.9 Hz, C4H),
6.04 (d, 1H, 3JHH = 9.8 Hz, C2H), 6.06–6.64 (m, 2H, ArH), 7.10–7.21
(m, 13H, ArH). 19F NMR (CDCl3, 282 MHz):
2JFH = 47.1 Hz, JFH = 18.3 Hz).
d
À22.0 (dd,
3
Acknowledgements
We are grateful to the University Grants Commission (UGC),
New Delhi, for the financial assistance (36-194/2008-SR). One of
the authors (A.K.) thanks to the Council of Scientific and Industrial
Research (CSIR), New Delhi, for senior research fellowship (09/135
(0604)/2010-EMR-I).
References
[31] X.-F. Duan, J. Zeng, J.-W. Lu, Z.-B. Zhang, J. Org. Chem. 71 (2006) 9873–9876.
[32] S. Hou, B. Huang, J. Wang, W. Zhang, Huaxue Shizi. 24 (2002) 240–241.
[1] J.T. Welch, Tetrahedron 43 (1987) 3123–3197.