Synthesis and characterization of novel trifluoromethyl-containing alcohols with Ruppert's reagent

Article abstract of DOI:10.1016/j.jfluchem.2011.07.020

Synthesis and characterization of novel new trifluoromethyl-containing alcohols using Ruppert's reagent [(trimethyl)trifluoromethylsilane] (1) are reported. The reactions of 1 with various ketones and aldehydes, such as tetraphenylcyclopentadienone (2a),

Full text of DOI:10.1016/j.jfluchem.2011.07.020

Journal of Fluorine Chemistry 133 (2012) 20–26
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis and characterization of novel trifluoromethyl-containing alcohols
with Ruppert’s reagent
*
Rajendra P. Singh, Jean’ne M. Shreeve
Department of Chemistry, University of Idaho, Moscow, ID 83844-2343, USA
A R T I C L E I N F O
A B S T R A C T
Article history:
Synthesis and characterization of novel new trifluoromethyl-containing alcohols using Ruppert’s
reagent [(trimethyl)trifluoromethylsilane] (1) are reported. The reactions of 1 with various ketones and
aldehydes, such as tetraphenylcyclopentadienone (2a), 9,10-anthraquinone (2b), pyrenaldehyde (2c),
2,6-dimethyl-para-anisaldehyde (2d), and 2,3(methylenedioxy)benzaldehyde (2e) in the presence of a
catalytic amount of tetrabutylammonium fluoride in THF led to the formation of the corresponding
trifluoromethylated silyl ether derivatives 3a–e in almost quantitative yields. Acid hydrolysis of 3a–e
gave the desired trifluoromethylated alcohol derivatives (4a–e) in excellent isolated yields. Compounds
were characterized by IR, NMR (1H, 19F, 13C NMR), GCMS, and elemental analysis. Single crystal X-ray
structures of 4a and 4b support the proposed products.
Received 26 June 2011
Received in revised form 16 July 2011
Accepted 19 July 2011
Available online 26 July 2011
Keywords:
Nucleophilic trifluoromethylation
(Trifluoromethyl)trimethylsilane
(Ruppert’s reagent)
ß 2011 Elsevier B.V. All rights reserved.
Tetraphenylcyclopentadienone
9,10-Anthraquinone
Pyrenaldehyde
X-ray crystallography
1. Introduction
2. Results and discussion
Fluorine is the most electronegative element. Therefore, the
incorporation of trifluoromethyl group into an organic molecule
changes dramatically its physical, chemical, and biological
properties [1,2]. The concomitant changes in properties make
these compounds suitable for diverse applications in material
sciences, and agro chemistry, as well as in the pharmaceutical
industry [3–6]. The biological activity [7,8] and numerous
commercial applications [9–12] of organo fluorine compounds
have encouraged interest in the development of synthetic methods
for selective and efficient incorporation of trifluoromethyl groups
into organic compounds under mild reaction conditions. Ruppert’s
reagent [(trimethyl)trifluoromethylsilane] is a well known nucle-
ophilic trifluoromethylating reagent which allows introducing the
trifluoromethyl group directly by reaction of substrates such as
aldehydes, ketones, and esters. Earlier we and others have shown
various applications of this methodology [13–21]. Here we report
the synthesis and characterization of some novel trifluoromethy-
lated alcohols using this reagent.
Tetraphenylcyclopentadienone (2a) was reacted with
1.25 equivalent of Ruppert’s reagent (1) in the presence of a
catalytic amount of tetrabutylammonium fluoride in THF at room
temperature (Scheme 1). The reaction was monitored by gas
chromatography.
Based on NMR the yield of the trimethylsilyl ether intermediate
(3a) was quantitative. Interestingly, 3a, was found to be
hydrolytically stable. Washing the reaction mixture with water
and extracting the product with dichloromethane gave pure 3a in
95% yield. The hydrolysis of 3a was first attempted with a mixture
of concentrated hydrochloric acid and THF (1:1) at room
temperature for a few hours but no significant hydrolysis was
observed (based on NMR). However, when the mixture was heated
at 70 8C for 12 h, hydrolysis was found to be complete (Scheme 1).
The product was extracted with dichloromethane and purified by
crystallization with dichloromethane/hexane (2:1) to give pure 4a
in 90% yield. See crystal structure (Fig. 1).
Next the reaction of 9,10-anthraquinone (2b) was carried out
with 2.25 equivalents of 1 in THF vide supra in order to make the
bis(trifluoromethyl)diol derivative (4b). The formation of the
trimethylsilyl ether intermediate (3b) was quantitative based on
NMR. The hydrolysis of 3b went smoothly with concentrated
hydrochloric acid and THF at room temperature in 3 h (Scheme 2).
The hydrolyzed derivative (4b) was extracted with dichloro-
* Corresponding author. Fax: +1 208 885 9146.
E-mail address: jshreeve@uidaho.edu (J.M. Shreeve).
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.07.020

R.P. Singh, J.M. Shreeve / Journal of Fluorine Chemistry 133 (2012) 20–26
21
O
Me3SiO
HO
CF3
CF3
Conc. HCl/
THF (1:1)
TMS-CF3 (1)
70 oC, 12 h
THF, TBAF (cat.)
2a
3a
4a
Scheme 1.
Fig. 1. (a) ORTEP diagram of compound 4a and (b) crystal packing diagram of 4a.
O
O
CF3
CF3
Me3SiO
Me3SiO
CF3
HO
HO
Conc. HCl/
THF (1:1)
TMS-CF3 (1)
R.T., 3 h
THF, TBAF (cat.)
CF3
3b
2b
4b
Scheme 2.
methane and purified by crystallization with dichloromethane/
hexane (2:1) to afford pure 4b in 88% yield. See crystal structure
(Fig. 2).
2,2,2-Trifluoro-1-(1-pyrenyl)ethanol (4c) is a valuable com-
pound as reported in the literature [22–24]. Earlier, the synthesis of
this compound was reported [25] by the conversion of pyrene into
1-(trifluoroacetyl)pyrene in 65% yield by using Me2SÁBF3 in
trifluoroacetic anhydride at À78 8C. However, reduction of the
ketone group in 1-(trifluoroacetyl)-pyrene using sodium borohy-
dride at 0 8C gave 2,2,2-trifluoro-1-(1-pyrenyl)ethanol (4c) in 95%
yield (Scheme 3). In our present work, the aldehyde (2c) is reacted
with 1.25 equivalent of Ruppert’s reagent, 1, and a catalytic
amount of TBAF in THF at ambient temperature to yield the
corresponding trimethylsilyl ether (3c) in quantitative yield (based
on NMR). The hydrolysis of 3c was carried out with concentrated
hydrochloric acid and THF mixture (1:1) at room temperature for
3 h to achieve 2,2,2-trifluoro-1-(1-pyrenyl)ethanol (4c) in 96%
isolated yield (Scheme 3).
Fig. 2. (a) ORTEP diagram of compound 4b and (b) crystal packing diagram of 4b.

22
R.P. Singh, J.M. Shreeve / Journal of Fluorine Chemistry 133 (2012) 20–26
OH
O
F3C
CF3
(CH3)2S.BF3
(CF3CO)2O
-78 oC/RT, Argon
NaBH4
Methanol, 0 oC/RT
4c
OH
F3C
F3C
OSiMe3
CHO
1, THF
Conc. HCl
THF, R.T., 3 h
TBAF (cat.)
2c
4c
3c
Scheme 3.
Using Ruppert’s reagent, aldehydes, 2d–e were also reacted. The
125.0 Æ 0.6 ppm with J values falling between 280 and 288 Hz in 3a–
e. For compounds 4a–e, the characteristic peaks in the proton NMR
spectra due to the hydroxyl proton appeared at 2.90 in 4a, 5.21 ppm
in 4b, 2.78 ppm in 4c, 3.26 ppm in 4d, and 3.15 ppm in 4e,
respectively. In the 19F NMR spectra, signals due to CF3 group
appeared as a singlet at À70.60 ppm in 4a, À77.95 in 4b where as in
3c–e it appeared as a doublet at À77 Æ 1.6 ppm. In 13C NMR the CF3
carbon appeared as a quartet at 125.0 Æ 0.5 ppm with J values
between 280 and 287 Hz in 4a–e. The chemical shifts for CF3 in the
fluorine NMR spectra for compounds 3a–e and 4a–e are shown in
Table 1.
X-ray quality crystals of compounds 4a and 4b were grown
from a mixture of chloroform/hexane (1:1). Their structures are
presented in Figs. 1 and 2. Selected bond lengths and bond angles
are given in Tables 2 and 3, respectively. Crystallographic data are
given in Table 4. Both, 4a and 4b are monoclinic and crystallize in
the P21/c space group. Compound 4b shows an interesting
hydrogen bonding pattern. The proposed structures of 4a and
4b are in agreement with X-ray analysis.
reactionsproceedwellinTHFinthepresenceofa catalyticamountof
TBAF. Based on NMR spectral analyses, the intermediates, 3d–e,
were formed quantitatively. Hydrolysis of 3d–e with concentrated
hydrochloric acid in THF at room temperature produced trifluor-
omethylatedproducts(4d–e)inexcellentisolatedyields(Scheme4).
All trifluoromethylated alcohol derivatives (4a–e) were fully
characterized by IR, NMR, GCMS, and elemental analysis. Some of
the trimethylsilyl intermediates were also characterized by
spectroscopic and elemental analysis to prove their structures.
The characteristic peaks in the proton NMR spectra of the
trifluoromethylated silyl ether intermediates (3a–e) showed a
singlet resonance at about 0.1 ppm arising from the trimethylsilyl
group. The CH proton bonded to the same carbon as the CF3 group
appeared as a quartet at 6.20 ppm in 3c, 5.14 ppm in 3d, and
5.18 ppm in 3e, respectively. In the 19F NMR spectra, signals due to
the CF3 group appeared as a singlet at À70.60 ppm in 3a, À77.95 in
3b whereas in 3c–e it was seen as a doublet at À77 Æ 1.6 ppm. In
the 13C NMR spectra, the CF3 carbon appeared as a quartet at
F3C
OSiMe3
F3C
OH
CHO
1, THF
Conc. HCl
THF, R.T., 3 h
TBAF (cat.)
O
O
O
2d
3d
4d
F3C
OSiMe3
O
F3C
OH
CHO
O
O
O
O
1, THF
Conc. HCl
THF, R.T., 3 h
TBAF (cat.)
O
2e
3e
4e
Scheme 4.

R.P. Singh, J.M. Shreeve / Journal of Fluorine Chemistry 133 (2012) 20–26
23
Table 1
Reaction of ketones (2a, b) and aldehydes (2c–e) with (trimethyl)trifluoromethylsilane.a
Substrate
Intermediateb
19F NMR (
d
)
Product
Yield (%)c
89
19F NMR (
d)
À70.60
À72.88
F3C
O
F3C
OSiMe3
OH
2a
4a
OH
3a
OSiMe3
À77.95
88
À78.65
F3C
F3C
O
F3C
F3C
OH
4b
OH
OSiMe3
3b
O
2b
À76.90
96
À77.33
F3C
F3C
CHO
OSiMe3
2c
3c
4c
OH
À78.11
92
À78.49
CHO
F3C
F3C
OSiMe3
O
O
O
2d
3d
4d
OH
À78.46
94
À77.78
F3C
OSiMe3
CHO
F3C
O
O
O
O
O
O
2e
4e
3e
a
b
c
All thereactions were carried out with5 mmol ofsubstrate, 5.25mmol of TMS-CF3 and0.1 mmol of TBAF in 10mL of anhydrous THF (for 2b 10.25 mmol of TMS-CF3 was used).
Yield of silylether intermediates is essentially quantitative based on 19F NMR.
Isolated yield.
Table 3
Selected bond angles (8) for compounds 4a and 4b.
4a
4b
Table 2
O(6)–C(1)–C(7)
O(6)–C(1)–C(5)
C(7)–C(1)–C(5)
O(6)–C(1)–C(2)
C(7)–C(1)–C(2)
C(5)–C(1)–C(2)
C(3)–C(2)–C(12)
C(3)–C(2)–C(1)
C(12)–C(2)–C(1)
C(2)–C(3)–C(18)
C(2)–C(3)–C(4)
C(18)–C(3)–C(4)
C(5)–C(4)–C(24)
C(5)–C(4)–C(3)
C(24)–C(4)–C(3)
C(4)–C(5)–C(30)
C(4)–C(5)–C(1)
C(30)–C(5)–C(1)
C(1)–O(6)–H(6)
104.32(16)
114.53(16)
110.76(18)
113.87(16)
110.26(17)
103.24(15)
128.75(17)
108.68(17)
122.54(16)
128.71(17)
109.62(16)
121.59(16)
126.84(18)
109.94(17)
123.19(16)
127.28(19)
108.49(17)
124.11(17)
109.4(14)
O(8)–C(1)–C(5)
O(8)–C(1)–C(2)
C(5)–C(1)–C(2)
O(8)–C(1)–C(9)
C(5)–C(1)–C(9)
C(2)–C(1)–C(9)
C(3)–C(2)–C(1)
C(4)–C(3)–C(2)
C(4)–C(3)–H(3)
C(2)–C(3)–H(3)
C(3)–C(4)–H(4)
C(6)–C(5)–C(1)
C(1)–O(8)–H(8)
F(12)–C(9)–F(11)
F(12)–C(9)–F(10)
F(11)–C(9)–F(10)
F(12)–C(9)–C(1)
F(11)–C(9)–C(1)
F(10)–C(9)–C(1)
112.86(10)
112.46(10)
114.05(10)
102.75(9)
106.91(9)
106.80(9)
118.48(11)
120.77(12)
119.6
˚
Selected bond lengths (A) for compounds 4a and 4b.
4a
4b
C(1)–O(6)
C(1)–C(7)
C(1)–C(5)
C(1)–C(2)
C(2)–C(3)
C(2)–C(12)
C(3)–C(18)
C(3)–C(4)
C(4)–C(5)
C(4)–C(24)
C(5)–C(30)
O(6)–H(6)
C(7)–F(10)
C(7)–F(9)
C(7)–F(8)
1.415(2)
1.528(3)
1.528(3)
1.533(3)
1.339(3)
1.483(3)
1.487(3)
1.492(3)
1.342(3)
1.478(3)
1.476(3)
0.96(2)
C(1)–O(8)
C(1)–C(5)
C(1)–C(2)
C(1)–C(9)
C(2)–C(3)
C(3)–C(4)
C(3)–H(3)
C(4)–H(4)
C(5)–C(6)
C(6)–C(7)
C(6)–H(6)
C(7)–H(7)
O(8)–H(8)
C(9)–F(12)
C(9)–F(11)
1.4221(14)
1.5223(17)
1.5280(16)
1.5549(16)
1.4016(17)
1.3907(18)
0.9500
119.6
120.1
0.9500
118.42(11)
109.5
1.4051(17)
1.3858(19)
0.9500
107.63(10)
107.31(10)
105.96(9)
110.32(10)
112.68(10)
112.63(10)
0.9500
1.325(3)
1.332(3)
1.333(2)
0.8400
1.3359(14)
1.3411(14)

24
R.P. Singh, J.M. Shreeve / Journal of Fluorine Chemistry 133 (2012) 20–26
Table 4
with aSMART APEX II CCD detector. The crystals were irradiated using
graphite monochromated MoK radiation ( = 0.71073). An Oxford
Selected crystal data and refinement details for compounds 4a and 4b.
a
l
Cobra low temperature device was used to keep the crystals at a
constant 293(2) K (4a) or 100(2) K (4b) during data collection.
Data collection was performed and the unit cell was initially
refined using APEX2 [v2010.3-0] [26]. Data Reduction was
performed using SAINT [v7.60A] [27] and XPREP [v2008/2] [28].
Corrections were applied for Lorentz, polarization, and absorption
effects using SADABS [v2008/1] [29]. The structure was solved and
refined with the aid of the programs in the SHELXTL-plus [v2008/4]
system of programs [30]. The full-matrix least-squares refinement
on F2 included atomic coordinates and anisotropic thermal
parameters for all non-H atoms. The H atoms were included using
a riding model.
4a
4b
Chemical formula
FW
C31H25F3O2
486.51
Monoclinic
P21/c
C16H10F6O2
348.24
Monoclinic
P21/c
Crystal system
Space group
Temperature (K)
293(2)
14.237(2)
17.734(3)
10.2900(16)
90
100(2)
5.7441 (11)
7.2930(14)
16.168(3)
90
˚
a (A)
˚
b (A)
˚
c (A)
a
b
g
(8)
(8)
(8)
99.136(3)
90
97.618(3)
90
3
˚
V (A )
2565.1(7)
4
671.3(2)
2
Z
Density (calculated) (mg/m3)
1.620
1.723
m
(mmÀ1
)
0.092
0.168
4.2. 1-Trifluoromethyl-2,3,4,5-tetraphenylcyclopentadiene-1-
F(0 0 0)
1016
352
trimethylsilylether (3a)
R1
0.0475
0.21 Â 0.14 Â 0.06
23,154
5254
0.0285
0.37 Â 0.34 Â 0.28
5910
Crystal size (mm3)
Reflections collected
Independent reflections
Rint.
Tetraphenylcyclopentadienone (2a) (5 mmol) and (trimethyl)-
trifluoromethylsilane (1) (5.25 mmol) were dissolved in tetrahy-
drofuran (10 mL) and a catalytic amount of tetrabutylammonium
fluoride (0.1 mmol) was added at 10 8C. After 10 min stirring, the
cold bath was removed and stirring was continued at 25 8C. for
24 h. Based on fluorine NMR, the yield of 3a was quantitative. All of
the volatile materials were removed at reduced pressure. The
crude product was purified by crystallization using a dichlor-
omethane/hexane mixture (2:1). Yield: 95%; IR (KBr pellet): 3056,
2959, 1599, 1490, 1443, 1254, 1171, 1097, 1072, 1029, 889, 844,
1361
0.0457
2708
0.0161
1609
Observed [I > 2s(I)] reflections
No. of parameters
Goodness-of-fit
333
111
1005
1041
3. Conclusions
Application of Ruppert’s reagent in the synthesis of some novel
trifluoromethyl containing alcohol derivatives has been described
by direct nucleophilic trifluoromethylation reactions from their
corresponding ketones or aldehydes. The trimethylsilyl ether
intermediates are formed in almost quantitative yield and their
acid hydrolysis afforded the corresponding trifluoromethylated
alcohols in excellent isolated yield. The proposed structures of 1-
732, 697 cmÀ1
; d 0.12 (s, 9H), 6.82–7.50 (m,
1H NMR (CD3CN):
20H); 19F NMR (CD3CN):
d
À70.60 (s, 3F); 13C NMR (CD3CN):
d 1.88,
88.0 (q, J = 28.0 Hz), 124.7 (q, J = 287.4 Hz), 127.17, 127.31, 127.4,
127.69, 128.2, 129.6, 130.6; MS (EI) m/z: 526 (M+), 457, 406, 289,
178, 77, 73; Elemental analysis calcd. for C33H29F3OSi: C, 75.26; H,
5.55. Found: C, 74.51; H, 5.43.
trifluoromethyl-2,3,4,5-tetraphenylcyclopentadiene-1-ol
and
4.3. 1-Trifluoromethyl-2,3,4,5-tetraphenylcyclopentadiene-1-ol (4a)
9,10-bis(trifluoromethyl)-9.10-dihydroxyanthracene have been
confirmed by single crystal X-ray analysis.
The silyl ether derivative 3a (4 mmol) was dissolved in
tetrahydrofuran (10 mL) and concentrated hydrochloric acid
(10 mL) was added. The reaction mixture was heated at 70 8C
for 20 h. It was cooled and mixed with dichloromethane (25 mL)
and washed with water (2Â 50 mL). The dichloromethane layer is
separated and dried over anhydrous magnesium sulfate and
filtered. Removal of solvent at reduced pressure gave 4a as a white
solid which was purified by crystallization with a dichloro-
methane/hexane mixture (2:1). Yield: 90%; IR (KBr pellet): 3541,
3055, 1599, 1489, 1440, 1253, 1169, 1144, 1071, 1028, 909, 731,
4. Experimental
All the reactions were carried out in a dry nitrogen atmosphere.
(Trifluoromethyl)-trimethylsilane and tetrabutylammonium fluo-
ride (1 M solution in THF) were purchased from Aldrich. Sample
preparation of all trimethylsilyl ether intermediates for spectro-
scopic measurements was carried out under nitrogen atmosphere
and anhydrous solvents were used. 1H, 19F, and 13C NMR spectra
were recorded in CDCl3 on a Bruker spectrometer operating at 300,
282, and 76 MHz, respectively. Chemical shifts are reported in ppm
698 cmÀ1; 1H NMR (CDCl3):
d
2.90 (s, 1H), 6.85–7.40 (m, 20H); 19
89.1 (q,
F
NMR (CDCl3):
d
72.88 (s, 3F); 13C NMR (CDCl3):
d
relative to the appropriate standard, CFCl3 for 19F and TMS for 1
H
J = 28.2 Hz), 125.0 (q, J = 286.5 Hz), 127.5, 127.8, 127.9, 128.0,
128.2, 129.9, 130.7, 133.9, 140.0, 147.7; MS (EI) m/z (species, rel.
int.): 454 (M+, 100), 406, 385 (M+ÀCF3, 10), 279, 178, 105, 77
(C6H5+, 15); Elemental analysis calcd. for C30H21F3O: C, 79.28; H,
4.66. Found: C, 78.74; H, 4.70.
and 13C NMR spectra. Infrared spectra were recorded using a BIO-
RAD FT spectrometer. For liquid compounds, a liquid film between
KBr discs was used and for solids, KBr pellets were prepared.
Melting points were obtained by using a Mel-Temp II apparatus.
Mass spectra were recorded on a Shimadzu 5050 spectrometer.
Elemental analyses were obtained by using a CE-440 elemental
analyzer (EAI Exeter Analytical). Suitable single crystals for 4a and
4b were grown using a mixture of chloroform and hexane (1:1).
4.4. 9,10-Bis(trifluoromethyl)-9.10-
bis(trimethylsiloxy)anthracene(3b)
The reaction was carried out as for 3a using 9,10-anthraquinone
4.1. X-ray crystallographic details for compounds 4a and 4b
(2b)
(5 mmol)
and
(trimethyl)trifluoromethylsilane
(1)
(10.25 mmol). Based on fluorine NMR, the intermediate 3b is
A colorless plate crystal (4a) of dimensions 0.21 mm  0.14 mm
 0.06 mm, or an irregular colorless crystal (4b) of dimensions
0.37 mm  0.34 mm  0.28 mm was mounted on a MiteGen Micro-
Mesh using a small amount of Cargille Immersion Oil. Data were
collected on a Bruker three-circle platform diffractometer equipped
formed quantitatively. IR (KBr pellets): 2968, 1674, 1601, 1447,
1409, 1319, 1260, 1174, 1076, 943, 875, 843, 763, 703 cmÀ1 1H
;
NMR (CDCl3):
NMR (CDCl3):
d F
0.06 (s, 18H), 7.4–7.6 (m, 4H), 7.8–8.1 (m, 4H); 19
d
À77.95 (s, 6F); 13C NMR (CDCl3):
d 2.5, 75.9 (q,
J = 28 Hz), 125.6 (q, 288 Hz), 128.4, 129.6, 130.0, 130.5 (q, J = 3 Hz),

R.P. Singh, J.M. Shreeve / Journal of Fluorine Chemistry 133 (2012) 20–26
25
131.3, 133.8, 134.3149.0; MS (EI) m/z: 373 (M+ÀF), 423 (M+ÀCF3),
by silica-gel chromatography using ethylacetate/hexane (1:3)
mixture. Yield: 92%; IR (neat on KBr window): 3410, 2951, 1616,
1512, 1463, 1294, 1258, 1166, 1124, 1100, 843, 758, 685 cmÀ1; 1H
353, 316, 288, 211, 73.
4.5. 9,10-Bis(trifluoromethyl)-9.10-dihydroxyanthracene(4b)
NMR (CDCl3): d 2.21 (s, 3H), 3.26 (broad, s, 1H), 3.85 (s, 3H), 5.25
(dq, 1H, J = 13.0 Hz, J = 6.6 Hz), 6.65 (s, 2H); 19F NMR (CDCl3):
d
Compound 3b is dissolved in 10 mL of THF and concentrated
hydrochloric acid (10 mL) was added. It was stirred at 25 8C for 3 h,
and treated as for 4a. 4b is a white solid which was crystallized
with chloroform/hexane (2:1) mixture. Yield: 88%; IR (KBr pellets):
3534, 2444, 1483, 1446, 1328, 1211, 1172, 1030, 911, 773, 694,
À77.78 (d, 3F, J = 6.6 Hz); 13C NMR (CDCl3):
d 16.7, 56.2, 69.4 (q,
J = 32.0 Hz), 112.9, 124.7 (q, 280.5 Hz), 129.9, 36.1, 159.0; MS (EI)
m/z: 234 (M+), 165, 137, 122, 91, 69; Elemental analysis calcd. for
C11H13F3O2: C, 56.41; H, 5.59. Found: C, 54.95; H, 6.02.
627 cmÀ1; 1H NMR (CDCl3):
d
5.21 (s, 2H), 7.61 (s, 4H), 8.03 (s, 4H);
4.10. 2,2,2-Trifluoro-1-(2,3-methylenedioxyphenyl)ethanol (4e)
19F NMR (CDCl3):
d
À78.65 (s, 3F); 13C NMR (CDCl3):
d 73.7 (q,
J = 27 Hz), 118.1, 125.5 (q, 286 Hz) 129.31 (q, J = 2.8 Hz), 130.1; MS
(EI) m/z (species, rel. int.): 348 (M+, 1), 279 (M+ÀCF3, 55), 210
The reaction is carried out as for 3a using 2,3-methylenediox-
yphenyl benzaldehyde (2e) with stirring at 25 8C for 5 h. Based on
NMR the trimethylsilylether intermediate (3e) is formed quanti-
tatively. An aliquot was drawn from the reaction mixture and the
solvent was removed at reduced pressure and spectroscopic data
were collected for 3e. To the remainder of the reaction mixture,
concentrated hydrochloric acid (10 mL) was added and the
reaction mixture was stirred at 25 8C for 3 h. It was mixed with
dichloromethane (10 mL) and washed with water (2Â 25 mL). The
dichloromethane layer is separated and dried over magnesium
sulfate and filtered. Removal of solvent at reduced pressure gave 4e
as liquid product which was purified by silica-gel chromatography
using ethyl acetate/hexane mixture (1:3).
(M+À2CF3,
100),
181
[M+À(2CF3 + COH),
25],
152
[M+À(2CF3 + 2COH), 20], 105 (C6H4COH+, 20), 76 (C6H4, 15), 69
(CF3+, 10); Elemental analysis calcd. for C16H10F6O2: C, 55.18; H,
2.89. Found: C, 55.05; H, 2.84.
4.6. 2,2,2-Trifluoro-1-trimethylsiloxy-1-pyrene (3c)
The reaction was carried out as for 3a using pyrenaldehyde (2c)
(5 mmol). Based on fluorine NMR, the intermediate white solid 3c
was formed quantitatively. 1H NMR (CDCl3):
d
0.24 (s, 9H), 6.20 (q,
1H, J = 6.5 Hz), 8.0–8.5 (m, 9H), 19F NMR (CDCl3):
À76.90 (d, 3F,
J = 6.5 Hz); 13C NMR (CDCl3):
d
d
À0.06, À70.4 (q, J = 32.2 Hz), 122.4,
124.8 (q, 285 Hz), 125.1, 125.6, 125.9, 126.3, 126.4, 127.5, 128.24,
128.8, 129.1, 130.6, 131.5, 132.1; MS (EI) m/z: 372 (M+), 303
(M+ÀCF3), 233, 201, 73.
4.11. 2,2,2-Trifluoro-1-(2,3-
methylenedioxyphenyl)trimethylsilylether (3e)
IR (neat on KBr disc): 2963, 2901, 1464, 1365, 1243, 1176, 1130,
4.7. 2,2,2-Trifluoro-1-pyreneethanol (4c)
1055, 991, 933, 873, 845, 731 cmÀ1; 1H NMR (CDCl3):
d
5.18 (q, 1H,
J = 6.5 Hz), 5.97 (d, 1H, J = 1.5 Hz), 6.00 (1H, J = 1.5 Hz), 6.8–6.91, m,
(2H), 7.07 (d, J = 7.5 Hz); 19F NMR (CDCl3):
À78.46 (d, 3F,
J = 6.5 Hz); 13C NMR (CDCl3):
67.75 (q, J = 33.4 Hz), 101.4, 109.2,
Compound 3c is treated as for 4b. Removal of solvent at reduced
pressure gave 4c as white solid which was crystallized from
dichloromethane. Yield: 96%; IR (KBr pellets): 1302, 1249,
11991116, 1080, 887, 839, 755, 694 cmÀ1 1H NMR (CDCl3):
d
d
120.9, 121.9, 124.4 (q, J = 280.5 Hz), 145.7, 147.4; MS (EI) m/z: 234
(M+), 165 (M+–CF3), 137, 122, 105, 91, 77, 69.
d
2.78 (d, 1H, J = 4.5 Hz), 6.18 (dq, 1H, J = 11 Hz, J = 6.3 Hz), 8.0–8.35
(m, 9H), 19F NMR (CDCl3):
(CDCl3):
d
À77.33 (d, 3F, J = 6.5 Hz); 13C NMR
4.12. 2,2,2-Trifluoro-1-(2,3-methylenedioxyphenyl)ethanol (4e)
d
69.58 (q, J = 30.3 Hz), 122.2, 124.8, 124.9, 125.0 (q,
J = 280 Hz), 125.1, 125.2, 125.8, 126.1, 126.5, 128.4, 128.8, 129.4,
130.6, 131.5, 132.3; MS (EI) m/z: 300 (M+), 231, 203, 202, 100, 69.
Elemental analysis calcd. for C16H10F6O2: C, 72.00; H, 3.69; Found:
C, 71.84; H, 3.63.
Yield: 94%; IR (liquid): 3455, 2904, 1605, 1466, 1359, 1249, 1175,
1128, 1049,980, 930, 835, 796, 771, 731, 689 cmÀ1; 1H NMR(CDCl3):
d
3.15 (d, 1H, J = 6.6 Hz), 5.10 (dq, 1H, J = 13.4 Hz, J = 6.7 Hz), 5.96 (d,
2H, J = 6.0 Hz), 6.70–6.95 (m, 3H); 19F NMR (CDCl3):
À78.49 (d, 3F,
J = 6.5 Hz); 13C NMR (CDCl3):
69.1 (q, J = 33.0 Hz), 101.5, 109.6,
d
d
4.8. 2,2,2-Trifluoro-1-(2,6-dimethyl-4-
115.9, 120.5, 122.2, 124.5 (q, 280.8 Hz), 145.8, 147.7; MS (EI) m/z:
220 (M+, 40), 151, 123, 93, 75, 65; Elemental analysis calcd. for
C9H7F3O3: C, 49.10; H, 3.20. Found: C, 49.17; H, 3.23.
methoxyphenyl)trimethylsilylether (3d)
The reaction is carried out as for 3a using 2,6-dimethyl-4-
methoxybenzaldehyde (2d) with stirring at 25 8C for 5 h. All the
solvents were removed at reduced pressure. The resulting liquid is
mixed with ether and hexane (10 mL, 1:1 mixture) and filtered
through a small pipette of silica gel to remove TBAF. Removal of
solvent at reduced pressure gave the desired trimethylsilyl ether
derivative (3d) as a liquid. Yield: 90%; IR (liquid): 2958, 1614, 1506,
Supplementary data
Crystallographic data for compounds 4a and 4b have been
deposited with the Cambridge Crystallographic Data Center
allocated deposit numbers CCDC 831455 and 831456. A copy of
the data can be obtained free of charge on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK. Fax: +44 1223 336033, e mail:
deposit@ccdc.ac.uk.
1254, 1177, 1133, 1035, 880, 843 cmÀ1; 1H NMR (CDCl3):
d 0.11 (s,
9H), 2.26 (s, 3H), 3.82 (s, 3H), 5.14 (q, 1H, J = 6.7 Hz), 6.60 (s, 1H),
7.35 (s, 1H); 19F NMR (CDCl3):
(CDCl3):
(q, 281.0 Hz) 130.6, 158.1; MS (EI) m/z (species, rel. int.): 306 (M+,
50), 237, 163, 77, 73; Elemental analysis calcd. for C14H21F3O2Si: C,
54.88; H, 6.91. Found: C, 54.71; H, 6.94.
d
À78.11 (d, 3F, J = 6.5 Hz); 13C NMR
Acknowledgement
d
À0.08, 16.2, 55.3, 69.5 (q, J = 32.0 Hz), 111.7, 119.4, 124.5
The authors gratefully acknowledge the support of ONR
(N00014-10-1-0097).
References
4.9. 2,2,2-Trifluoro-1-(2,6-dimethyl-4-methoxyphenyl)ethanol (4d)
[1] J.T. Welch, Tetrahedron 43 (1987) 3123–3197.
[2] R. Filler, Y. Kobayashi (Eds.), Biomedical Aspects of Fluorine Chemistry, Kodansha
Ltd., Elsevier, Tokyo, Amsterdam, 1982.
The silylether derivative (3d) (4 mmol) was treated as for 4b.
Removal of solvent at reduced pressure gave 4d which was purified

26
R.P. Singh, J.M. Shreeve / Journal of Fluorine Chemistry 133 (2012) 20–26
[3] G.A. Olah, R.D. Chambers, G.K.S. Prakash (Eds.), Synthetic Fluorine Chemistry,
Wiley, New York, 1992.
[14] R.P. Singh, A. Vij, R.L. Kirchmeier, J.M. Shreeve, J. Fluorine Chem. 98 (1999) 127–
132.
[4] J.F. Liebman, A. Greenberg, W.R. Dolbier, Jr. (Eds.), Fluorine Containing Molecules:
Structure, Reactivity, Synthesis, and Applications, VHC, New York, 1988.
[5] J.T. Welch, S. Eshwarakrishnan (Eds.), Fluorine in Bioorganic Chemistry, Wiley,
New York, 1991.
[15] R.P. Singh, R.L. Kirchmeier, J.M. Shreeve, Org. Lett. 1 (1999) 1047–1049.
[16] R.P. Singh, A. Vij, R.L. Kirchmeier, J.M. Shreeve, Inorg. Chem. 39 (2000) 375–377.
[17] R.P. Singh, G. Cao, R.L. Kirchmeier, J.M. Shreeve, J. Org. Chem. 64 (1999) 2873–
2876.
[6] R. Filler, Y. Kobayashi (Eds.), Organofluorine Compounds in Medicinal. Chemistry
and Biomedical Applications, Elsevier, Amsterdam, 1993.
[7] Y. Kobayashi, I. Kumadaki, Acc. Chem. Res. 11 (1978) 197–204.
[8] C. Hansch, A. Leo (Eds.), Substituents Constants for Correlation Analysis in
Chemistry and Biology, Wiley, New York, 1997.
[18] R.P. Singh, J.M. Shreeve, J. Org. Chem. 65 (2000) 3241–3243.
[19] R.P. Singh, J.M. Shreeve, Tetrahedron 56 (2000) 7613–7632.
[20] R.P. Singh, J.M. Leitch, B. Twamley, J.M. Shreeve, J. Org. Chem. 66 (2001) 1436–1440.
[21] (a) G.K.S. Prakash, A.K. Yudin, Chem. Rev. 97 (1997) 757–786;
(b) G.P. Stahly, D.R. Bell, J. Org. Chem. 54 (1989) 2873–2877.
[9] R.E. Banks, B.E. Smart, J.C. Tatlow (Eds.), Organofluorine Chemistry, Principles and
Commercial Applications, Plenum Press, New York, 1994.
[10] V.A. Solonoshock (Ed.), Enantiocontrolled Synthesis of Fluoro-organic Com-
pounds: Stereochemical Challenges and Biomedical Targets, Wiley, New York,
1999.
[11] V.P. Khukhar, V.A. Soloshonok (Eds.), Fluorine-containing Amino Acids: Synthesis
and Applications, Wiley, 1995.
[12] D.M. Walba, H.A. Razavi, N.A. Clark, D.S. Parnar, J. Am. Chem. Soc. 110 (1988)
8686–8691.
[22] M. Li, J. Gardella, D.K. Bwambok, B. El-Zahab, S. de Rooy, M. Cole, M. Lowry, I.M.
Warner, J. Comb. Chem. 11 (2009) 1105–1114.
[23] W.H. Pirkle, J.M. Finn, J. Org. Chem. 46 (1981) 2935–2938.
[24] A. Munoz, M. Sanchez, T. Junk, A. Virgili, J. Org. Chem. 65 (2000) 5069–5071.
[25] A. Munoz, A. Virgili, Tetrahedron Asymmetry 13 (2002) 1529–1534.
[26] Bruker, APEX2 v2010.3-0, Bruker AXS Inc., Madison, Wisconsin, USA, 2010.
[27] Bruker, SAINT v7.68A, Bruker AXS Inc., Madison, Wisconsin, USA, 2009.
[28] Bruker, XPREP v2008/2, Bruker AXS Inc., Madison, Wisconsin, USA, 2008.
[29] Bruker, SADABS v2008/1, Bruker AXS Inc., Madison, Wisconsin, USA, 2008.
[30] Bruker, SHELXTL v2008/4, Bruker AXS Inc., Madison, Wisconsin, USA, 2008.
[13] R.P. Singh, R.L. Kirchmeier, J.M. Shreeve, J. Org. Chem. 64 (1999) 2579–2581.