EWG assisted nucleophilic fluorination using PPHF: A strategy for the synthesis of 1,2,2-triaryl-2-fluoroethanones

Article abstract of DOI:10.1016/j.tet.2011.08.083

The nucleophilic fluorination of 1,2,2-triaryl-2-hydroxyethanones by fluoride ion has been carried out using pyridinium poly(hydrogen fluoride) (PPHF) to give 1,2,2-triaryl-2-fluoroethanones in fairly good yield. The presence of electron withdrawing group

Full text of DOI:10.1016/j.tet.2011.08.083

Tetrahedron 67 (2011) 8308e8313
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
EWG assisted nucleophilic fluorination using PPHF: a strategy for the synthesis of
1,2,2-triaryl-2-fluoroethanones
*
Anil Kumar, Anil K. Pal, Rishi D. Anand, Tej V. Singh , Paloth Venugopalan
Department of Chemistry and Centre of Advanced Studies in Chemistry, Panjab University, Chandigarh 160014, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The nucleophilic fluorination of 1,2,2-triaryl-2-hydroxyethanones by fluoride ion has been carried out
using pyridinium poly(hydrogen fluoride) (PPHF) to give 1,2,2-triaryl-2-fluoroethanones in fairly good
yield. The presence of electron withdrawing group (EWG), such as eCOAr at the carbon bearing hydroxyl
Received 9 February 2011
Received in revised form 24 August 2011
Accepted 27 August 2011
group facilitates such nucleophilic fluorination. The intermediacy of bridged oxiranyl ion and
a-keto-
Available online 1 September 2011
carbenium ion has been proposed for the formation of various
rivatives respectively.
a-fluoroketones and benzofuran de-
Keywords:
Ó 2011 Elsevier Ltd. All rights reserved.
1,2,2-Triaryl-2-fluoroethanones
Nucleophilic fluorination
PPHF
Bridged oxiranyl ion
1. Introduction
been reported using nucleophilic sources of fluorine, such as KF in
18-crown-6, tetraethylammonium fluoride (TEAF), TlF3 and pyr-
idinium poly(hydrogen fluoride) (PPHF) with HgO or NCS or
NBS.4b,7 The leaving group, such as halogen or Nþ2 in these reactions
has been introduced before fluorination.
Since a large number of natural and synthetic compounds are
alcohols, carboxylic acids and hydroxyketones, the fluorinating
agent, which can react selectively with oxygen functionality would
be a suitable one. The direct replacement of hydroxyl group by
nucleophilic fluorine has been carried out using reagents, such as
PPHF, diethylaminosulphur trifluoride (DAST) and Ishikawa reagent
(CF3CHFCF2NEt2þCF3CF¼CFNEt2).7e,8e10 Keeping in view of the
nature of substrate, reaction, work up conditions, commercial
availability and handling, PPHF is a reagent of choice. In this
backdrop, we envisaged that, if it becomes viable to replace the
Fluorine containing organic compounds have important role in
biochemistry, material science and medicinal chemistry.1 Approx-
imately 20% of drugs in the market contain fluorine and this
number is expected to grow.2 The enhanced biological activity,
binding interaction and stability of CeF bond in these compounds
make them suitable as drug molecules.3 In particular,
a-fluoro
acetophenone (1-aryl-2-fluoroethanone) and its derivatives can
produce a number of interesting molecules used in pharmaceutical
and agrochemical industry.4 A number of reagents have been dis-
covered for fluorination of organic compounds depending on the
type of functionality.5 Fluorination at
a-position of acetophenone
and its derivatives can occur by replacing hydrogen or hetero atoms
(O, N) using either electrophilic or nucleophilic source of fluorine
respectively. The electrophilic methods use F2, CF3OF, CsSO4F or
reagents such as N-fluoro-o-benzenedisulfonimide (NFOBS), N-
hydroxyl group in 1,1-diaryl methanols or a-hydroxyketones with
PPHF, it would be an important and effective strategy for the flu-
orodehydroxylation in these classes of compounds. It is further
anticipated that the end products of such fluorodehydroxylation
can function as versatile synthetic intermediates, which may find
applications in fluorine substituted bioactive compounds.11 In this
paper, such advances leading to the desired a-fluoroketones and
the role of different electron withdrawing groups (EWG) present at
the carbon bearing hydroxyl group are presented.
fluorodiphenyldisulfonimide
(NFSi),
1-fluoro-4-hydroxy-1,4-
diazoniabicyclo [2.2.2] octane bis(tetrafluoroborate) (Accufluor-
NFTh) and 1-fluoro-4-chloromethyl-1,4-diazoniabicyclo [2.2.2] oc-
tane bis(tetrafluoroborate) (Selectfluor).4b,6 The intermediate in-
volved in these reactions is either an enol or trialkylsilylenol ether.
In the later case, a strong base is used to generate an enolate, which
is trapped by trialkylchlorosilane. Both intermediates form a-fluo-
roketones with electrophilic fluorine. Similarly, a few methods have
2. Results and discussion
1,2,2-Triaryl-2-hydroxyethanones can be considered as having
1,1-diaryl methanol and benzoyl moieties (EWG). Since fluorination
* Corresponding author. Tel.:þ91 172 2534439; fax:þ91 172 2545074; e-mail
address: tvs@pu.ac.in (T.V. Singh).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.083

A. Kumar et al. / Tetrahedron 67 (2011) 8308e8313
8309
of 1,1-diaryl methanol derivatives12 using PPHF has not been re-
ported, attempts have been made towards their fluorodehydrox-
ylation.13a The positive outcome of such a reaction would provide
us an effective methodology to replace eOH group with Fꢀ in these
class of compounds. Towards this objective, 1aef were treated with
PPHF at ambient temperature. The compounds 1aed gave only
corresponding bis (1,1-diphenylmethyl) ethers, 2aed13 (Scheme 1,
Table 1). 1-(4-Nitrophenyl)-1-phenyl methanol (1e) yielded both
ether and fluoroalkane; bis[1-(4-nitrophenyl)-1-phenylmethyl]
ether (2e, 33%) and 1-fluoro-1-(4-nitrophenyl)-1-phenyl methane,
(3a, 43%). While the treatment of bis[1-(3-nitrophenyl)] methanol
(1f) with PPHF under similar conditions gave only 1-fluoro-bis[1-
(3-nitrophenyl)] methane (3b, 62%) (Scheme 2, Table 1). These
compounds were characterised by various spectral data (See
Experimental section).
(3a). In this case nitro group (being electron withdrawing) is ex-
pected to increase the electrophilicity of E00 to such an extent that
both the nucleophiles 1e and fluoride ion attack the electrophile E00
to give ether 2e as well as fluoro product 3a. The presence of two
nitro groups in case of 1f further increases the electrophilicity of E00
to greater extent. As the nucleophilicity of fluoride ion is more than
that of alcohols, the electrophile has been attacked by the fluoride
ion only to give the corresponding fluoro compound (3b) exclu-
sively (see also Scheme 6). In a nutshell, more the presence of EWGs
at any position of the aromatic ring(s), more will be the fluoride ion
attack. It may thus be inferred from the above observations that the
alcohols bearing electron withdrawing group(s) under the prevail-
ing reaction conditions can produce the desired fluorinated product.
It is further envisaged that alcohols bearing an electron withdraw-
ing group (EWG) like eCOAr or eCOOH bonded directly to carbon
bearing hydroxyl group may be capable of providing fluoro product.
In order to investigate this hypothesis that nucleophilic sub-
stitution of hydroxyl group by fluoride ion (Fꢀ) using PPHF is ac-
tivated by electron withdrawing group present at the carbon
bearing hydroxyl group, benzilic acid, which has the required
positioning of carboxylic group, was selected. To benzilic acid in
dry THF was added PPHF at 0 ꢁC and was stirred at room tem-
Ar2
C
Ar2
C
Ar2
C
Ar2
C
H+
1a-d
+
Ar1
OH
Ar1
OH2
Ar1
O
Ar1
PPHF
H
H
H
H
1a-d
E'
2a-d
Scheme 1. Formation of 2aed, from the reaction of 1,1-diaryl methanols, 1aed with
PPHF.
perature for 15
h (Scheme 3). The organic compound was
extracted with DCM, washed with water, brine and dried. Removal
of solvent yielded only 2-fluoro-2,2-diphenylethanoic acid 5 in
53% yield. The formation of any other product including corre-
sponding ether was not detected by TLC analysis of the crude
reaction mixture. The compound 5 was characterised by IR, 1H
NMR, 13C NMR, 19F NMR and mass spectral data. The IR showed
absorption bands at 1720 cmꢀ1 and 3350 cmꢀ1 for carbonyl and
hydroxyl group, respectively. 19F NMR spectrum showed a signal at
Table 1
Isolated yields of ethers, 2aee and fluoro compounds, 3a, b
Compound
Ar1
Ar2
Yield (%)
2a
2b
2c
2d
2e
3a
3b
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
3-NO2C6H4
C6H5
72
67
49
43
33
43
62
4-CH3C6H4
4-OCH3C6H4
2-FC6H4
4-NO2C6H4
4-NO2C6H4
3-NO2C6H4
d
ꢀ139 (s).
Ar2
C
Ar2
1e
Ar1
O
C
H
Ar1
PPHF
C
COOH
C
F
COOH
15 h, rt
Ar2
H
Ar2
2e
H+
OH
+
OH2
Ar1
C
OH
Ar1
C
PPHF
4
5
H
Ar2
H
Scheme 3. Fluorodehydroxylation of benzilic acid, 4, using PPHF.
F-
E''
1e-f
Ar1
C
F
1e: Ar1 = C6H5, Ar2 = 4-NO2C6H4
1f: Ar1 Ar2 = 3-NO2C6H4
The successful fluorodehydroxylation of benzilic acid, which
delineated the role of EWG like eCOOH leading to the desired
product prompted us to investigate the reaction of -hydrox-
yketones, such as 6aeh (Scheme 4). In these reactions, the electron
withdrawing group is eCOAr. 1,2,2-Triaryl-2-hydroxyoethanones
6aeh14 were reacted with PPHF in ice-cold solution in dry THF.
The contents were stirred at room temperature for appropriate
time period. The reaction was quenched with ice-cold liquor am-
monia and products were obtained by usual work up. These were
purified by flash chromatography to give products 7aeh. The time
=
H
3a and 3b
a
Scheme 2. Formation of 2e, 3a and 3b, from the reaction of 1e and 1f with PPHF.
1H NMR spectra of ethers (2aee) displayed characteristic singlet
d 5.26e5.67 (s, 2H) for benzhydrylic protons and multiplets at
6.78e7.98 for the aromatic protons, whereas in fluoro compounds
at
d
3a and 3b, benzhydrylic proton appeared as a doublet at
d 6.48 (d,
1H, 2JHF¼47 Hz) and
d
6.54 (d, 1H, 2JHF¼47.1 Hz) respectively due to
for fluorination, yield of products and physical state of the a-fluo-
the presence of fluorine on the same carbon atom. The aromatic
roketones are summarised in Table 2. The benzofuran derivative 8
(yield 22%) and 9 (yield 14%) were also obtained from the reaction
of 6b and 6d under the above mentioned reaction conditions. 1,2,2-
Triaryl-2-fluoroethanones have been characterised using various
spectral data (See experimental).
protons displayed signal quite downfield upto d 8.24. The presence
of a doublet at
d
94.5 (d, 1JCF¼174.6 Hz) and
d
90.4 (d, 1JCF¼178.6 Hz)
for the carbon bearing fluorine in 13C NMR spectra of 3a and 3b,
respectively further supports their structure formulae.
It is interesting to note that secondary alcohols 1aed do not give
the corresponding fluoro compounds but gave bis(diarylmethyl)
ethers. In the first step, the alcohol may get protonated to give
electrophile E0, which would be attacked by 1aed to give ethers
2aed in the second step (Scheme 1). The electrophilicity of E0 may
be just sufficient towards the attack of alcoholic nucleophiles, 1aed
and not for the Fꢀ. Interestingly 1e on treatment with PPHF gave
both products, ether (2e) as well as corresponding fluoro compound
The IR spectra of a-fluoroketones showed absorption bands for
the carbonyl stretching in the range of 1675e1695 cmꢀ1. The
compound 6a absorbs at 1665 cmꢀ1 and 7a at 1675 cmꢀ1. Electron
withdrawing group (F) attached to
a-carbon generally increases
C]O stretching frequency. The planar geometry between phenyl
and carbonyl groups have also been affected by steric factors, which
reduces conjugation between phenyl and carbonyl groups to give

8310
A. Kumar et al. / Tetrahedron 67 (2011) 8308e8313
Ar3
C
appeared as doublet. The compounds 7aee and 7h showed at
d 198
Ar3
C
Ar3
PPHF, THF
rt, 24-48 h
while 7f and 7g displayed it at 202.8. The higher chemical shift for
d
Ar1
C
O
Ar2
Ar1
C
O
Ar2
C]O in 7f and 7g may be due to presence of alkyl group on the
phenyl ring attached to the carbonyl group. Fluorine bearing carbon
(CeF) showed intensive splitting and high coupling constant values
O
Ar1
F
OH
8-9
Ar1 = 1-C6H5 Ar3 = 1-C10H7
9. Ar1 = C6H5, Ar3 = 2-C2H5C6H4
7a-h
6a-h
8
(d, JCFw180e189 Hz). The molecular ion is absent in almost all a-
fluoroketones. The high resolution mass spectra of fragment ion of
7aeh however showed exact masses, which supported their mo-
lecular formulae. 1H NMR spectrum of 8 and 9 showed multiplet for
Scheme 4. Products, 7aeh and 8, 9 formed in the reaction of a-hydroxyketones, 6aeh,
with PPHF.
aromatic protons in the range of
d
7.07e7.83. 13C NMR did not give
Table 2
Reaction time, isolated yields and melting point of
a
-fluoroketones, 7aeh
indication for the presence of fluorine (JCeF is missing) and carbonyl
group. The mass spectra of 8 showed molecular ion at m/z 320 and
at m/z 298 for 9 as a base peak. Based on the above data (along with
that given in the Experimental section), 8 and 9 were assigned as 3-
(1-naphthyl)-2-phenyl benzofuran and 3-(2-ethylphenyl)-2-
phenyl benzofuran, respectively.
The excess of HF in PPHF (30% pyridine, 70% hydrogen fluoride)
is capable of protonating the 3ꢁ alcoholic group to give protonated
1,2,2-triaryl-2-hydroxyethanones (A) (Scheme 5). One would ex-
pect that the attack of nucleophile (Fꢀ) is involved in the rate de-
termining step as in SN2 mechanism. If the nucleophile has little
bonding to the transition state of A, it has almost the full loss of
leaving group H2O (analogous to SN1 type mechanism).15 The
Entry Ar1
Ar2
Ar3
Time (h) Yield (%) Mp (ꢁC)
7a
7b
7c
7d
7e
7f
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
1-C10H7
24
48
76
37 (22)a 114e115
80 66e68
46 (14)a 42e44
73e74
C6H5
C6H5
C6H5
C6H5
2-CH3C6H4 C6H5
2-C2H5C6H4 C6H5
2-CH3C6H4 28
2-C2H5C6H4 25
4-CH3C6H4 48
C6H5
C6H5
57
69
55
60
Oil
39e40
Oil
24
24
24
7g
7h
4-CH3C6H4 4-CH3C6H4 C6H5
Oil
a
The yields given in parentheses are for rearranged products 8 and 9.
rise to more double bond character for pC]O group and results in
higher value of nC]O. The planarity remains undisturbed in
oroketones, such as 7a, which shows nC]O at 1675 cmꢀ1, while
other compounds show in between 1680e1690 cmꢀ1
The 1H NMR spectra of all
-fluoroketones exhibited multiplet
for aromatic protons in the range of 6.68e7.99. Compounds 7aee
and 7h showed their ortho aromatic protons (2H) downfield in the
range of 7.80e7.99, whereas in case of 7f and 7g, alkyl group has
a-flu-
protonated
ion to give
a
-hydroxyketones (A) may be attacked by the fluoride
a-fluoroketones 7aeh (path a). Alternatively the loss of
.
water molecule in A can lead to either bridged oxiranyl ion B (Path
b) or -ketocarbenium ion C (Path c). These intermediates can ei-
a
a
d
ther exist exclusively as one of themselves or in varying proportions
(which may be in equilibrium). The intermediate B may also be
attacked by the fluoride ion to give a-fluoroketones 7aeh. The in-
d
occupied one ortho position on the phenyl group and it seems that
it shields the ortho proton and consequently ortho protons merge
into multiplets for other aromatic protons. Therefore, 7f and 7g do
termediate C (depending upon the conformational stability and
subtle stereoelectronic factors) may adopt the conformation D,
which can undergo 4p-electrocyclization to give benzofuran de-
rivatives (8 and 9).16 Though such cyclizations are reported by
Reynolds17 and Creary,18 their plausible existence in fluorodehy-
droxylation using PPHF is reported here for the first time. However,
it is to be noted that the formation of benzofuran derivatives is not
always mutually exclusive, in two cases (6b and 6d), both products
not exhibit separate signals for ortho protons. a-Fluoroketones have
also been analysed by 19F NMR spectra, which showed chemical
shift as singlet confirm the presence of fluorine. 13C NMR spectra of
all
a-fluoroketones showed splitting of carbonyl carbon due to
coupling between fluorine and carbonyl carbon atom and it
Ar3
C
Ar3
Path a
Ar3
C
-
+
F
H
Ar1
C
Ar2
Ar1
C
O
C
Ar2
Ar1
C
O
Ar2
-H2 O
O
OH
OH2
F
7a-h
A
6a-h
Path b
-H O
Path c
-
F
-H O
2
2
Ar3
Ar1
Ar3
Ar2
Ar3
Ar2
Ar1
O
Ar1
O
O
D
C
B
Ar3
Ar1
Ar3
Ar1
+
8. Ar1 = C6 H5, Ar3 = 1-C10 H7
9. Ar1 = C6 H5, Ar3 = 2-C 2 H5 C6 H4
-H
O
O
H
8 and 9
Scheme 5. Mechanism for the formation of a-fluoroketones, 7aeh and benzofuran derivatives, 8, 9, by the reaction of a-hydroxyketones, 6aeh, with PPHF.

A. Kumar et al. / Tetrahedron 67 (2011) 8308e8313
8311
are isolated. The formation of benzofuran derivatives only in two
cases suggests that the intermediate of C type does not exist in
other cases (6a, 6c and 6eeh). Therefore, all the a-fluoroketones
may form from A or B, which indicates that reaction proceeds via
SN2 type mechanism. Though we still do not have any concrete
evidence for the existence of B and C, from the above mentioned
observations and literature,8 it is proposed that the reaction is of
75.53 MHz, respectively, with TMS as an internal standard. 19F NMR
spectra were performed on JEOL ECX 300 spectrometer operating at
282.56 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 CFCl3. Coupling constants are in
hertz. Mass spectra were recorded at 70 eV using VG analytical
11e250-J 70S. The relative intensities are given in parentheses. CHN
analyses were recorded using Flash EA 1112 series CHNS-O Analyser.
SN2 type. Scheme 5 explains the formation of a-fluoroketones 7aeh
and benzofuran derivatives 8 and 9.
Flash chromatography was performed by using 40e63 m
In general, the formation of fluoro compounds and/or ethers can
be explained by the Scheme 6. The protonation of (Q) by PPHF
would generate an electrophile (Eþ), which can react with nucle-
ophile, such as Fꢀ and/or (Q) to form corresponding fluoro com-
pound and/or ether. Water is the other product of the reaction.
(230e400 mesh) silica gel. PPHF was obtained from SigmaeAldrich.
4.2. General procedure for the reaction of 1,1-diaryl
methanols (1aef) with PPHF
A
solution of 1,1-diaryl methanol, 1aef (0.2e1.0 g,
0.73e5.43mmol)wastakeninaplasticbottle(13.4cmꢂ5.6cm)indry
THF. PPHF (1.5e3.0 mL) was added to the stirred solution at ice-cold
temperature. The contents were further stirred for 6e24 h and the
reaction mixture was quenched with liquor ammonia at ice-cold
temperature. The organic compound was extracted with DCM,
washed with Na2CO3 (10%) solution, water, brine and dried over an-
hydrous Na2SO4. The solvent was removed under reduced pressure to
afford viscous oil, which was purified by flash column chromatogra-
phy to give products 2aee, 3a and 3b in varying yields of 33e72%.
Ar
C
F
Ar
F- and/or Q
R
H+
Ar
Ar
Ar
Ar
C
OH2
C
OH
and/or
(PPHF)
- H2O
R
(E+)
R
(Ar)2C
R
O
C(Ar)2
R
(Q)
Ar = Phenyl or substituted phenyl ring (s)
R = H, -COOH, -COAr
Scheme 6. Plausible product distribution in the fluorodehydroxylation reaction using
PPHF.
4.2.1. Bis(1,1-diphenylmethyl) ether (2a). Yield 0.68 g (72%). Col-
ourless solid, mp: 109e110 ꢁC (lit.13a mp 107e109 ꢁC).
The fluoride anion has the higher nucleophilicity parameter
than alcohols19 and the EWG increases the electrophilicity of Eþ
present either in aromatic ring (s) or when it is attached to carbon
bearing hydroxyl group (R¼eCOOH, eCOAr). Considering the re-
action as the combination of nucleophile and electrophile and us-
ing the nucleophilicity and electrophilicity parameters, it is
predicted that the attack of fluoride ion relative to Q is more facile
on Eþ having EWG.20 Thus, EWG favors the formation of the fluoro
compounds and not the ethers.
4.2.2. Bis[1-(4-methylphenyl)-1-phenylmethyl] ether (2b)13b. Yield
0.64 g (67%). Viscous oil. 1H NMR (CDCl3, 300 MHz):
d
6.98e7.27 (m,
18H, ArH), 5.26 (s, 2H, OCH) 2.18 (s, 6H, CH3). 13C NMR (CDCl3,
75.53 MHz):
d 143.9, 140.9, 136.9, 129.0, 128.3, 127.2, 126.5, 126.4,
71.2, 21. LRMS m/z: 378 (Mþ, 0), 199 (14), 198 (80.6), 197 (24.7), 183
(47.2), 181 (10.5), 166 (11.3), 165 (23.9), 152 (8.4), 121 (25.7), 120
(19.1), 107 (11.2), 106 (11.5), 105 (100), 93 (52.8), 92 (67.6), 79 (20.9),
78 (19.4), 77 (68.1), 76 (6.4).
4.2.3. Bis[1-(4-methoxyphenyl)-1-phenylmethyl] ether (2c)13c. Yield
0.28 g (49%). Colourless solid. Mp: 121e122 ꢁC. 1H NMR (CDCl3,
3. Conclusion
300 MHz):
d
7.21e7.36 (m, 14H, ArH), 6.86 (d, 4H, ArH), 5.33 (s, 2H,
158.9,
It has been shown in this paper that it is possible to fluo-
rodehydroxylate the family of 1,2,2-triaryl-2-hydroxyoethanones
(6aeh) with PPHF leading to their corresponding fluoro com-
pounds (7aeh). The nucleophilic fluorination by fluoride ion is
facilitated by increasing the electrophilicity of Eþ, which can be
achieved by the presence of electron withdrawing groups, such as
eNO2, eCOOH and eCOAr. Compounds like 1,1-diaryl methanols
(1aed), which lack the assistance of such electron withdrawing
group yield only dimer like products, such as their ethers (2aed).
OCH), 3.78 (s, 6H, OCH3). 13C NMR (CDCl3, 75.53 MHz):
d
142.7, 142.5, 134.5, 134.3, 128.7, 127.8, 113.8, 69.1, 55.3. LRMS m/z:
410 (Mþ, 0.6), 214 (4.1), 213 (26.6), 198 (42.5), 197 (100), 196 (10),
182 (7.3), 166 (2.7), 165 (18.8), 154 (12), 153 (25.2), 152 (10.9), 135
(11.5), 105 (7.2), 106 (0.6), 92 (4.2), 77 (12.3).
4.2.4. Bis[1-(2-fluorophenyl)-1-phenylmethyl] ether (2d). Yield 0.42 g
(43%). Viscous oil. Rf (5% hexane/EtOAc) 0.66. 1H NMR (CDCl3,
300 MHz):
d 7.51e7.57 (m, 2H, ArH), 7.22e7.31 (m, 12H, ArH),
Formation of benzofuran derivatives 8 and 9 along with a-fluo-
roketones 7b and 7d, points towards the fact that the reactive
intermediate C may adopt requisite conformational positioning (D)
7.03e7.20 (m, 2H, ArH),
d 6.86e7.93 (m, 2H, ArH) 5.67 (d, 2H,
4JHF¼2.1 Hz OCH). 13C NMR (CDCl3, 75.53 MHz):
d 161.8
(1JCF¼245.2Hz),141.1,129.1,128.5,128.2,127.7,127.2,127.0,124.4,115.5
that can lead to 4p-electrocyclization. Such suitable topological
(4JCF¼19 Hz), 65.5. 19F NMR (CDCl3, 282.56 MHz):
ꢀ115.9 (m, ArF).
d
positioning may be dictated by stereoelectronic factors. Even in
such instances, the fluoride attack on reactive species is energet-
ically feasible and it is evidenced by the formation of both, the
cyclised product as well as the corresponding fluoro compounds.
4.2.5. Bis[1-(4-nitrophenyl)-1-phenylmethyl] ether (2e)13d,e. Yield
0.31 g (33%). Colourless solid. Mp: 56e58 ꢁC. Rf (10% hexane/EtOAc)
0.80. 1H NMR (CDCl3, 300 MHz):
d
8.06e8.12 (m, 4H, ArH), 7.43e7.48
(m, 4H, ArH), 7.10e7.21 (m, 10H, ArH), 5.38 (s, 2H, OCH). 13C NMR
4. Experimental
(CDCl3, 75.53MHz):d149.2, 147.4,147.2, 140.1, 139.7, 129.0, 128.7, 128.4,
127.5, 123.6, 79.7. LRMS m/z: 410 (Mþ, 0.6), 214 (4.8), 213 (26.6), 198
(42.5), 197 (100), 196 (10.0), 182 (7.3), 166 (2.7), 165 (18.8), 154 (12.0),
149 (25.2),152 (10.9),135 (11.5),105 (7.2),106 (0.6), 92 (4.2), 77 (12.3).
4.1. Equipments and chemicals
Melting points were taken in open capillaries and are un-
corrected. The IR spectra were recorded on PerkineElmer IR 1800
spectrophotometer. The 1H NMR and 13C NMR spectra were recorded
in CDCl3 on JEOL ECX 300 spectrometer operating at 300 MHz and
4.2.6. 1-Fluoro-1-(4-nitrophenyl)-1-phenyl methane (3a). Yield
0.42 g (43%). Colourless solid, Mp: 38e40 ꢁC. Rf (10% hexane/EtOAc)
0.68.1H NMR (CDCl3, 300 MHz):
d
8.12e8.15 (d, 2H, 3JHH¼8.4 Hz, ArH),

8312
A. Kumar et al. / Tetrahedron 67 (2011) 8308e8313
7.42e7.45 (m, 2H, 3JHH¼8.4 Hz, ArH), 7.22e7.32 (m, 5H, ArH), 6.48 (d,
0.35. IR (KBr): 1680 cmꢀ1 (CO). 1H NMR (CDCl3, 300 MHz):
2
1H, JHF¼47 Hz, CH). 13C NMR (CDCl3, 75.53 MHz):
d
147.6
d
7.87e7.96 (m, 2H, ArH), 7.25e7.58 (m, 15H, ArH). 13C NMR (CDCl3,
(2JCF¼23.2 Hz), 138.6 (2JCF¼20.5 Hz), 129.2, 128.9, 126.9, 126.8, 123.7,
75.53 MHz):
d
198.3 (d, 2JCF¼30.2 Hz, CO), 137.9, 137.6, 135.9, 135.3,
94.5 (1JCF¼174.6 Hz). 19F NMR (CDCl3, 282.56 MHz):
d
ꢀ166.6 (d,
134.6, 133.3, 130.7, 129.0, 128.9, 128.7, 128.4, 128.0, 126.7, 126.5,
2JFH¼47.1 Hz). LRMS m/z: 231 (Mþ,100), 232 (18), 230 (26), 214 (15.0),
185 (32), 184 (43), 183 (48), 166 (15), 165 (51), 152 (13), 109 (63), 108
(14),107 (35),101 (24), 83 (19), 77 (40). Anal. Calcd for C13H10FNO2: C,
67.53; H, 4.36; N, 6.06. Found: C, 67.55; H, 4.35; N, 6.05.
125.9, 124.3, 122.3, 105.6 (1JCF¼180.4 Hz, CF). 19F NMR (CDCl3,
282.56 MHz):
d
ꢀ136.8 (s). LRMS m/z: 340 (Mþ, 5.0), 320 (1.6), 235
(100.0), 216 (11.7), 215 (48.2), 106 (6.1), 105 (39), 77 (20.7). HRMS:
calcd for C24H17OF m/z 340.1263. Found 340.1290.
4.2.7. 1-Fluoro-bis[1-(3-nitrophenyl)] methane (3b). Yield 0.125 g
4.4.3. 3-(1-Naphthyl)-2-phenyl benzofuran (8)21. Yield 0.52 g (22%).
Colourless solid, Mp: 94e95 ꢁC. 1H NMR (CDCl3, 300 MHz):
62%. Colourless solid. Mp 95e96 ꢁC. Rf (10% hexane/EtOAc) 0.54. 1H
2
NMR (CDCl3, 300 MHz):
d
6.54e6.70 (d, 1H, JHF¼47.1 Hz, CHF),
d d 151.5,
7.11e7.83 (m, 16H, ArH). 13C NMR (CDCl3, 75.53 MHz):
7.57e7.69 (m, 4H, ArH), 8.21e8.24 (m, 4H, ArH). 13C NMR (CDCl3,
150.1, 134.8, 130.9, 130.6, 129.4, 129.0, 128.4, 127.8, 126.9, 126.8,
126.6, 126.2, 126.0, 124.3, 123.7, 123.1, 119.6, 112.2. LRMS: m/z 320
(Mþ, 33.6), 289 (3.3), 141 (11.0), 116 (5.6), 102 (6.0), 101 (100), 99
(5.1), 98 (28.5), 95 (4.7), 94 (46.5), 85 (10.1), 84 (7.0), 83 (80.6), 82
(11.9), 77 (2.4).
75.53 MHz):
d
148.5, 140.3 (d, 2JCF¼22.9 Hz), 132.1 (d, 3JCF¼6.3 Hz),
3
130.2, 124.0 (d, JCF¼1.8 Hz), 121.4 (d, JCF¼6.8 Hz), 90.4 (d,
1JCF¼178.6). 19F NMR (CDCl3, 282.56 MHz):
d
ꢀ167.7 (d,
2JFH¼46.5 Hz). Anal. Calcd for C13H9FN2O4: C, 56.52; H, 3.28; N,
10.14. Found: C, 56.48; H, 3.22; N, 10.19.
4.4.4. 2-Fluoro-2-(2-methylphenyl)-1,2-diphenylethanone
(7c). Yield 2.40 g (80%). Colourless solid, Mp: 66e68 ꢁC; Rf (10%
hexane/EtOAc) 0.39. IR (KBr): 1680 cmꢀ1 (CO). 1H NMR (CDCl3,
4.3. 2-Fluoro-2,2-diphenyl ethanoic acid (5)
A saturated solution of 2-hydroxy-2,2-diphenyl ethanoic acid, 4
(0.8 g, 3.5 mmol) in dry THF was taken in a plastic bottle. PPHF
(2 mL) was added to the stirred solution at ice-cold temperature.
The contents were further stirred for 15 h and the reaction mixture
was quenched with liquor ammonia at ice-cold temperature. The
organic compound was extracted with DCM, washed with water,
brine and dried over anhydrous Na2SO4. The solvent was removed
under reduced pressure to afford a viscous oil, which was purified
by flash chromatography (hexane/ethylacetate, 96:4) to yield
300 MHz): d 7.89e7.92 (m, 2H, ArH), 7.04e7.50 (m, 12H, ArH), 2.27
(d, 5JHF¼3.2 Hz, 3H, CH3). 13C NMR (CDCl3, 75.53 MHz):
d 198.2 (d,
2JCF¼30 Hz, CO), 138.0, 137.7, 135.3, 133.0, 132.1, 130.5, 129.3, 128.9,
128.8, 128.5, 126.7, 126.6, 125.3, 105.4 (d, 1JCF¼184.7 Hz, CF), 21.5. 19
F
NMR (CDCl3, 282.56 MHz):
d
ꢀ140.3 (s). LRMS m/z: 304 (Mþ, 0), 199
(33), 197 (0), 196 (5.7), 134 (7.0), 183 (12.3), 179 (12.9), 178 (12.1),
106 (9.7), 105 (100), 77 (19.9). HRMS: calcd for C14H12
F
(MþeC6H5CO) m/z 199.0923. Found 199.0922.
a white solid 5. Yield 0.42 g (53%). Mp: 135e136 ꢁC. IR (Nujol) nmax
3350 cmꢀ1 (OH), 1720 cmꢀ1 (CO). 1H NMR (CDCl3, 300 MHz):
:
4.4.5. 2-Fluoro-2-(2-ethylphenyl)-1,2-diphenylethanone (7d). Yield
1.10 g (46%). Colourless solid, Mp: 42e44 ꢁC; Rf (10% hexane/EtOAc)
0.40. IR (KBr): 1675 cmꢀ1 (CO). 1H NMR (CDCl3, 300 MHz):
d
6.80e7.70 (m, 10H, ArH). 13C NMR (CDCl3, 75.53 MHz):
d 80.9 (d,
1JCF¼187.2 Hz, CF), 126.6, 128.5, 129.4, 141.3 (d, 2JCF¼22.1 Hz), 178.5
d 7.83e7.86 (m, 2H, ArH), 7.45e6.68 (m, 12H, ArH), 2.50e2.58 (q,
(d, JCF¼18.7 Hz). 19F NMR (CDCl3, 282.56 MHz):
d
ꢀ139 (s). LRMS
2H, CH2), 1.10e1.15 (t, 3H, CH3). 13C NMR (CDCl3, 75.53 MHz):
2
m/z: 230 (Mþ, 0), 224 (46), 166 (100), 165 (94), 105 (49), 77 (37).
d
198.2 (d, 2JCF¼29.6 Hz, CO), 143.9, 138.2, 137.9, 137.6, 135.3, 133.0,
Anal. Calcd for C14H11FO2: C, 73.03; H, 4.82. Found: C, 73.10; H, 4.80.
130.4, 129.4, 128.9, 128.7, 128.5, 128.3, 126.7, 125.1, 105.2 (d,
1JCF¼184.7 Hz, CF), 27.1, 15.6. 19F NMR (CDCl3, 282.56 MHz):
4.4. General procedure for the fluorodehydroxylation of
hydroxyketones (6aeh)
a
-
d
ꢀ140.9 (s). LRMS m/z: 318 (Mþ, 0.8), 299 (2.5), 214 (15.0), 213
(81.9), 193 (10.3), 192 (9.3), 183 (4.0), 178 (13.6), 165 (4.4), 115 (9.9),
106 (7.8), 105 (100), 91 (2.4), 77 (2.8), 76 (19.1). HRMS: calcd for
C15H14F (MþeC6H5CO) m/z 213.1113. Found 213.1109.
A saturated solution of
a-hydroxyketone 6aeh (1.0e3.0 g,
3.2e9.6 mmol) in dry THF was taken in
a
plastic bottle
(13.4 cmꢂ5.6 cm). To this solution, PPHF (2.0e6.0 mL) was added at
ice-coldtemperature.Thetemperaturewasallowedtorisetoambient
temperature and the contents were stirred for 24e48 h. The reaction
mixture was quenched with ice-cold liquor ammonia. The organic
compound was extracted with DCM, washed with HCl (10%), Na2CO3
(10%), water, brine and dried over anhydrous Na2SO4. The solvent was
removed under reduced pressure to yield brown viscous oil, which
was purified by flash column chromatography (hexane/ethylacetate,
98:2) to give colourless product 7aeh and 8, 9 in varying yields.
4.4.6. 3-(2-Ethylphenyl)-2-phenyl benzofuran (9). Yield 0.32
(14%). Colourless oil. 1H NMR (CDCl3, 300 MHz):
7.07e7.63 (m,
13H, ArH), 2.97e3.05 (q, 2H, CH2), 1.40e1.46 (t, 3H, CH3). 13C NMR
(CDCl3, 75.53 MHz): 152.7, 150.1, 133.4, 131.1, 130.0, 129.0, 128.5,
128.3, 127.7, 127.2, 126.7, 126.2, 124.1, 123.3, 120.3, 117.8, 111.2, 23.2,
14.6. LRMS: m/z 298 (Mþ, 100), 299 (26.5), 284 (5.9), 283 (27.5), 241
(63.2), 211 (11.8), 178 (3.6), 141 (4.9), 134 (4.0), 126 (4.5), 105 (10.5),
77 (78.2).
g
d
d
4.4.7. 2-Fluoro-2-(4-methylphenyl)-1,2-diphenylethanone
4.4.1. 2-Fluoro-1,2,2-triphenylethanone (7a). Yield 2.30 g (76%).
Colourless solid, Mp: 73e74 ꢁC; Rf (10% hexane/EtOAc) 0.41. IR
(7e). Yield 1.15 g (57%). Colourless oil; Rf (10% hexane/EtOAc) 0.41.
IR (KBr): 1687 cmꢀ1 (CO). 1H NMR (CDCl3, 300 MHz):
d 7.89e7.91 (d,
(KBr): 1675 cmꢀ1 (CO). 1H NMR (CDCl3, 300 MHz):
d
7.96e7.99 (m,
2H, ArH), 7.48e7.52 (t, 1H, ArH), 7.36e7.40 (m, 7H, ArH), 7.21e7.24
2H, ArH), 7.26e7.58 (m, 13H, ArH). 13C NMR (CDCl3, 75.53 MHz):
(d, 2H, ArH), 7.14e7.16 (d, 2H, ArH), 2.15 (s, 3H, CH3). 13C NMR
d
197.9 (d, 2JCF¼30.5 Hz, CO), 139.4, 135.2, 133.2, 130.5, 128.8, 128.4,
(CDCl3, 75.53 MHz):
d
198.0 (d, 2JCF¼30.1 Hz, CO),139.3, 138.7, 136.3,
1
128.3, 126.7, 104.2 (d, JCF¼186.2 Hz, CF). 19F NMR (CDCl3,
135.2, 133.1, 130.5, 129.1, 128.7, 128.3, 128.2, 126.7, 126.7, 102.0 (d,
282.56 MHz):
d
ꢀ140.6 (s). LRMS m/z: 290 (Mþ, 0.2), 272 (0.2), 271
1JCF¼185.2 Hz, CF), 21.22. 19F NMR (CDCl3, 282.56 MHz):
d
ꢀ139.8
(0.3), 270 (0.2), 186 (9.3), 185 (54.3), 183 (15.7), 165 (17.5), 106 (9.7),
105 (100.0), 77 (22.2). HRMS: calcd for C13H10F (MþeC6H5CO) m/z
185.0766. Found 185.0761.
(s). HRMS: calcd for C14H12F (MþeC6H5CO) m/z 199.0923. Found
199.0918.
4.4.8. 2-Fluoro-1-(2-methylphenyl)-2,2-diphenylethanone
(7f). Yield 1.38 g (69%). Colourless solid, Mp: 39e40 ꢁC; Rf (10%
hexane/EtOAc) 0.42. IR (KBr): 1685 cmꢀ1 (CO). 1H NMR (CDCl3,
4.4.2. 2-Flouro-2-(1-naphthyl)-1,2-diphenylethanone
(7b). Yield
1.0 g (37%). Colourless solid, Mp: 114e115 ꢁC; Rf (10% hexane/EtOAc)

A. Kumar et al. / Tetrahedron 67 (2011) 8308e8313
8313
4. (a) Prakash, G. K. S.; Beier, P. Angew. Chem., Int. Ed. 2006, 45, 2172; (b) Fuglseth,
E.; Thvedt, T. H. K.; Moll, M. F.; Hoff, B. H. Tetrahedron 2008, 64, 7318; (c)
Heinrich, M. R. Tetrahedron Lett. 2007, 48, 3895; (d) Yoon, S. C.; Chao, J.; Kim, K.
J. Chem. Soc., Perkin Trans. 1 1998, 109; (e) Prakash, G. K. S.; Hu, J.; Olah, G. A. J.
Fluorine Chem. 2001, 112, 357.
5. (a) Lal, G. S.; Pez, G. P.; Syvret, R. G. Chem. Rev. 1996, 96, 1737; (b) Advances in
Organic Synthesis; Atta-Ur-Rahman, Laali, K. K., Eds.; Bentham Science Ltd.: Oak
Park, IL, 2006; Vol. 2; (c) New Fluorinating Agents in Organic Syntheses; German,
L., Zemskov, S., Eds.; Springer: New York, NY, 1989.
6. (a) Middleton, W. J.; Bingham, E. M. J. Am. Chem. Soc. 1980, 102, 4845; (b) Pu-
rington, S. T.; Lazaridis, N. V.; Bumgardener, C. L. Tetrahedron Lett. 1986, 27,
2715; (c) Appelman, E. H.; Basil, L. J.; Thompson, R. C. J. Am. Chem. Soc. 1979, 101,
3384; (d) Stavber, S.; Zupan, M. J. Chem. Soc., Chem. Commun. 1981, 795; (e)
Resnati, G.; DesMarteau, D. D. J. Org. Chem. 1991, 56, 4925; (f) Devis, F. A.; Han,
W.; Murphey, C. K. J. Org. Chem. 1995, 60, 4730; (g) Devis, F. A.; Han, W. Tet-
rahedron Lett. 1991, 32, 1631; (h) Stavber, S.; Zupan, M. Tetrahedron Lett. 1996, 37,
3591; (i) Thvedt, T. H. K.; Fuglseth, E.; Sundby, E.; Hoff, B. H. Tetrahedron 2009,
65, 9550; (j) Stavber, G.; Zupan, M.; Stavber, S. Tetrahedron Lett. 2007, 48, 2671;
(k) Stavber, G.; Zupan, M.; Stavber, S. Synlett 2009, 589; (l) Stavber, S.; Jereb, M.;
Zupan, M. Synthesis 2002, 2609.
7. (a) Leroy, J. J. Org. Chem. 1981, 46, 206; (b) Birdsall, N. J. M. Tetrahedron Lett. 1971,
28, 2675; (c) Rozen, S.; Filler, R. Tetrahedron 1985, 41, 1111; (d) Chen, Z.; Zhu, W.;
Zheng, Z.; Zou, X. J. Fluorine Chem. 2010, 131, 340; (e) Cantrell, G. L.; Filler, R. J.
Fluorine Chem. 1985, 27, 35; (f) Takaoka, A.; Iwakiri, H.; Ishikawa, N. Bull. Chem.
Soc. Jpn. 1979, 52, 3377.
300 MHz):
(CDCl3, 75.53 MHz):
d
7.06e7.48 (m, 14H, ArH), 2.29 (s, 3H, CH3). 13C NMR
d
202.8 (d, 2JCF¼30.2 Hz, CO),139.4,139.0,137.8,
136.6, 131.3, 130.9, 128.7, 128.4, 126.7, 126.6, 124.8, 103.6 (d,
1JCF¼187.6 Hz, CF), 20.5; 19F NMR (CDCl3, 282.56 MHz):
ꢀ140.2 (s).
d
LRMS m/z: 304 (Mþ, 0), 284 (1.4), 186 (4.1), 185 (22.6), 184 (3.7), 183
(10.8), 165 (15.3), 120 (12.9), 119 (100.0), 91 (31.8). HRMS: calcd for
C13H10F (MþꢀC7H7CO) m/z 185.0766. Found 185.0761.
4.4.9. 2-Fluoro-1-(2-ethylphenyl)-2,2-diphenylethanone (7g). Yield
0.60 g (55%). Colourless oil; Rf (10% hexane/EtOAc) 0.41. IR (KBr):
1680 cmꢀ1 (CO). 1H NMR (CDCl3, 300 MHz):
d 7.51e6.75 (m, 14H,
ArH), 2.55e2.62 (q, 2H, CH2), 1.14e1.11 (t, 3H, CH3). 13C NMR (CDCl3,
75.53 MHz):
d
202.7 (d, 2JCF¼33.9 Hz, CO), 143.9, 139.4, 139.1, 137.6,
136.4,133.0,131.0,130.4,129.8,129.4,128.7,128.2,126.6,125.1,124.8,
103.5 (d,1JCF¼189.3 Hz, CF), 26.6,15.5.19F NMR (CDCl3, 282.56 MHz):
d
ꢀ140.2 (s). LRMS m/z: 318 (Mþ, 0), 299 (4.5), 298 (15.6), 283 (4.9),
214 (19.3), 213 (31.7), 197 (7.5), 196 (9.6), 193 (12.6), 185 (49.9), 179
(4.4),178 (17.8),165 (5.5),152 (1.8),135 (10.8),133(100),116 (1.7),115
(13.2), 106 (11.2), 105 (52.2), 91 (5.4), 77 (22.4). HRMS: calcd for
C13H10F (MþeC8H9CO) m/z 185.0766. Found 185.0760.
8. Olah, G. A.; Welch, J. T.; Vankar, Y. D.; Nojima, M.; Kerekes, I.; Olah, J. A. J. Org.
Chem. 1979, 44, 3872.
9. (a) Dahbi, A.; Hamman, S.; Beguin, C. G. J. Chem. Res., Synop. 1989, 128; (b)
Dahbi, A.; Hamman, S.; Beguin, C. G. J. Chem. Res., Miniprint 1989, 1056.
10. (a) Denmark, S. E.; Wu, Z.; Crudden, C.; Matsuhashi, M. J. Org. Chem. 1987, 62,
8288; (b) Wilkinson, J. A. Chem. Rev. 1992, 92, 505; (c) Bergmann, E. D.; Cohen,
A. M. Isr. J. Chem. 1970, 8, 925; (d) Bergmann, E. D.; Cohen, A. M. Chem. Abstr.
1971, 75, 62645W.
4.4.10. 2-Fluoro-1,2-bis(4-methylphenyl)-2-phenylethanone
(7h). Yield 1.20 g (60%). Colourless oil; Rf (10% hexane/EtOAc) 0.42.
IR (KBr): 1690 cmꢀ1 (CO). 1H NMR (CDCl3, 300 MHz):
d 7.80e7.84
(m, 2H, ArH), 7.12e7.28 (m, 11H, ArH), 2.40 (s, 6H, CH3). 13C NMR
(CDCl3, 75.53 MHz):
d
197.4 (d, 2JCF¼29.0 Hz, CO),144.0,139.7, 139.4,
11. (a) Fluorine in Bioorganic Chemistry; Welch, J. T., Eswarakrishnan, S., Eds.; Wiley:
New York, NY, 1991; (b) Wetch, J. T. Tetrahedron 1987, 43, 3123.
138.6, 136.4, 132.6, 130.7, 130.3, 130.0, 129.7, 129.1, 128.9, 128.6,
12. (a) These were prepared by the reduction of various benzophenones with so-
dium borohydride in methanol. (b) Wiselogle, F. Y.; Sonneborn, H. Organic
Syntheses; John: New York, NY, USA, 1941; Collect. Vol. No. 1; 90; (c) Truett, W.
L.; Moulton, W. N. J. Am. Chem. Soc. 1951, 73, 5913 and references cited therein;
(d) Smith, B. B.; Leffler, J. E. J. Am. Chem. Soc. 1955, 77, 2509; (e) Stewart, B. B.;
Smith, H. A. J. Am. Chem. Soc. 1957, 79, 5457.
13. (a) Johnson, A. L. J. Org. Chem. 1982, 47, 5220; (b) Zhu, Z.; Espenson, J. H. J. Org.
Chem. 1996, 61, 324; (c) Rybakova, M. N. Zh. Obshch. Khim. 1966, 2, 470; (d)
Stavber, S.; Zupan, M. Tetrahedron Lett. 1993, 34, 4355; (e) Toda, F.; Takumi, H.;
Akehi, M. J. Chem. Soc., Chem. Commun. 1990, 1270.
128.2, 126.7, 121.1, 104.3 (d, 1JCF¼185.8 Hz, CF), 21.3, 21.2. 19F NMR
(CDCl3, 282.56 MHz):
d
ꢀ139.8 (s). LRMS m/z: 318 (Mþ, 0), 199
(46.0),183 (12.3),165 (5.6),120 (12.3),119 (100.0),105 (7.1), 97 (9.2),
91 (25.4), 85 (15.8), 71 (21.7). HRMS: calcd for C14H12
F
(MþeC7H7CO) m/z 199.0923. Found 199.0907.
Acknowledgements
14. (a) 1,2,2-Triaryl-2-hydroxyoethanones have been prepared by reacting the
appropriate Grignard reagent with benzil or its derivatives using the reported
procedures. (b) Easthan, J. F.; Huffaker, J. E.; Raaem, V. F.; Collins, C. J. J. Am.
Chem. Soc. 1956, 78, 4323; (c) Roger, R.; McGreger, A. J. Chem. Soc. 1934, 1, 442;
(d) Baddar, F. G.; Fahmy, F. M.; Aly, N. F. J. Ind. Chem. Soc. L 1973, 586.
15. Anslyn, E. V.;Daugherty, D. A. Modern Physical OrganicChemistry; University Science
Books: Sausalito, California, 2006, Chapter 8, pp 462 and Chapter 11, pp 646e648.
16. (a) Kitagawa, T.; Nishimura, M.; Takeuchi, K.; Okamoto, K. Tetrahedron Lett.1991, 32,
3187; (b) Dao, L.; Maleki, M.; Hopekinson, A.;Lee-Ruff, E. J. Am. Chem. Soc.1986,108,
5237; (c) Okamoto, K.; Takeuchi, K.; Kitagawa, T. Bull. Soc. Chim. Belg. 1982, 91, 410.
17. Reynolds, W. F.; Dais, P.; Maclntyre, D. W.; Topsom, R. D.; Marriott, S.; Nagy-
Falsobuki, E. V.; Taft, R. W. J. Am. Chem. Soc. 1983, 105, 378.
We are grateful to the University Grants Commission (UGC),
New Delhi, for providing 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 junior research fellow-
ship (09/135 (0604)/2010-EMR-I).
References and notes
18. (a) Creary, X. J. Am. Chem. Soc. 1984, 106, 5568; (b) Creary, X.; Hopkinson, A. C.;
Lee-Ruff, E. In Advances in Carbocation Chemistry; Creary, X., Ed.; JAI: Greenvich,
CT, 1989; Vol. 1, p 45.
1. (a) Fluorine in Medicinal Chemistry and Chemical Biology; Ojima, I., Ed.; J. Wiley:
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Wiley-VCH: Weinheim, 2004; (d) Begue, J.-P.; Bonnet-Delpon, D. J. Fluorine
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Angew. Chem., Int. Ed. 2000, 39, 4216.
19. (a) The nucleophilicities for Fꢀ and alcohols are 2.0 and 0.0, respectively
Pearson, R. G.; Sobel, H.; Songsted, J. J. Am. Chem. Soc. 1968, 90, 319; (b) Pearson,
R. G. Chemical Hardness; Wiley: New York, NY, 1997; (c) The real nucleophile is F
(HF)ꢀx in these reactions (Ref. 8).
20. Although the trend of electrophilicities of Eþ formed during the proposed
mechanism is not known, the increasing trend of electrophilic reactivities of
a few Michael acceptors with EWG (eCN, NO2) have been calculated by using
2. (a) Thayer, A. M. Chem. Eng. News 2006, 84, 15; (b) Thayer, A. M. Chem. Eng.
News 2006, 84, 27.
3. (a) Begue, J.-P.; Bonnet-Delpon, D. Bioorganic and Medicinal Chemistry of Fluo-
rine; John: New York, NY, 2008; (b) Tressaud, A.; Haufe, G. Fluorine and Health,
Molecular Imaging, Biomedical Materials and Pharmaceuticals; Elsevier: Am-
sterdam, 2008; (c) Hagmann, W. K. J. Med. Chem. 2008, 51, 4359 and references
cited therein; (d) Mayers, A. G.; Barbay, J. K.; Zhong, B. J. Am. Chem. Soc. 2001,
123, 7207; (e) Gree, R. Ind. J. Chem. 2000, 39B, 646.
ꢁ
equation log K20 ¼sN (NþE), where sN, sensitivity parameter; N, nucleophi-
C
licity and E stands for electrophilicity. This equation has also been used to
predict the rates (k) and reactivities: Appel, R.; Mayr, H. J. Am. Chem. Soc. 2011,
133, 8240 and references cited therein.
21. Colobert, F.; Castanet, A.-S.; Abillard, O. Eur. J. Org. Chem. 2005, 3334.