Synthetic utility of 2,3,3,3-tetrafluoroprop-1-ene (HFO-1234yf)

Article abstract of DOI:10.1016/j.jfluchem.2015.05.006

2,3,3,3-Tetrafluoroprop-1-ene, known as the environmentally benign fluorinated olefin recently employed for the car air-conditioning system, was proved to follow the addition-elimination sequence at its C² position by the reaction of a variety of alkoxides, forming CF₃-containing vinyl ethers in excellent yields.

Full text of DOI:10.1016/j.jfluchem.2015.05.006

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FLUOR-8563; No. of Pages 6
Journal of Fluorine Chemistry xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthetic utility of 2,3,3,3-tetrafluoroprop-1-ene (HFO-1234yf)
Yuya Hiraoka a, Tomoko Kawasaki-Takasuka a, Yoshitomi Morizawa b, Takashi Yamazaki a,
*
a Division of Applied Chemistry, Institute of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei 184-8588, Japan
b Asahi Glass Co. Ltd., Research Center, Kanagawa Ku, Yokohama 221-8755, Japan
A R T I C L E I N F O
A B S T R A C T
Article history:
2,3,3,3-Tetrafluoroprop-1-ene, known as the environmentally benign fluorinated olefin recently
employed for the car air-conditioning system, was proved to follow the addition–elimination sequence
at its C2 position by the reaction of a variety of alkoxides, forming CF3-containing vinyl ethers in excellent
yields.
Received 6 April 2015
Received in revised form 11 May 2015
Accepted 12 May 2015
Available online xxx
ß 2015 Elsevier B.V. All rights reserved.
Dedicated to Professor Iwao Ojima for his
70th birthday.
Keywords:
Addition–elimination reactions
Vinyl ethers
Trifluoromethyl group
Acetals
1. Introduction
levels and natural charges by using the Gaussian 09W software [4]
using the B3LYP/6-311 + + G** level of theory. As described in
2,3,3,3-Tetrafluoroprop-1-ene 1a (HFO-1234yf) has recently
been drawing significant attention as the potent fluorinated
refrigerant with the global warming potential of only 4, no ozone
depleting potential, and a very short atmospheric lifetime of ca. 11
days [1]. Moreover, its similar thermophysical performance to
widely used HFC-124a at present [2] allowed to launch its
installation to air-conditioning systems for vehicles on markets
and thus, their production in an industrial scale should open a
readily available route of this interesting partially fluorinated
alkene 1a whose previous synthetic application was limited
mainly to preparation of polymer materials [3]. Then, we have
started our research for clarification of its reactivity from the
synthetic point of view, and found out that 1a smoothly reacted
with alkoxides by the well-known addition–elimination sequence
which was reported in detail in this article.
Table 1, introduction of fluorine atoms to the propene framework
was found to give a significant impact. For example, trifluorination
at C3 like the case of 1a–e allowed to significantly decrease the
frontier orbital energy levels from the ones of the prototypical
counterpart 1g, which should endow clear activation of these
molecules toward a variety of nucleophiles. Moreover, the vinylic
fluorine atom affected the electronic circumstance around the
carbon–carbon double bond on the basis of the so-called p–
p
repulsive interaction [5], rendering the carbon C2 possessing this
unique atom electropositive (1a and f). The same trend albeit
weakly was noticed for the compound 1e with a methoxy group at
the C2 position, while bromine in the same halogen family did not
indicate such a special feature at all (see, 1c). Combination of these
two characteristic information led us to strong anticipation that
anionic species would preferentially react with 1a at the C2 site in
spite of the already reported SN20 type reactions of appropriate
nucleophiles to 1b–d [6,7].
2. Results and discussion
First of all, we have searched adequate types of nucleophiles
using such representative reagents as benzyl alcohol, benzylamine,
thiophenol, diethyl malonate, and phenol (Entries 1–5 in Table 2).
Thus, a solution containing Nuꢀ species generated by simple
mixing of nucleophiles (NuH) and bases (1.1 equiv to NuH) in a
solvent indicated was transferred to a pressure tight reactor where
1.2 equiv of 1a was introduced. After 0.5 h reaction at room
temperature, it was found out that benzyl alcohol was the only one
Before starting our synthetic study, computation was per-
formed for the representative seven compounds 1a–g for
comparison of the basic information on frontier orbital energy
*
Corresponding author. Tel.: +81 42 388 7038; fax: +81 42 388 7038.
E-mail address: tyamazak@cc.tuat.ac.jp (T. Yamazaki).
http://dx.doi.org/10.1016/j.jfluchem.2015.05.006
0022-1139/ß 2015 Elsevier B.V. All rights reserved.
Please cite this article in press as: Y. Hiraoka, et al., J. Fluorine Chem. (2015), http://dx.doi.org/10.1016/j.jfluchem.2015.05.006

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Table 1
Representative physical properties of prop-1-enesa.
.
Energy level (eV)
HOMO
Natural charge
X
Y
LUMO
C1
C2
0.318
C3
1.017
F
F (1a)
ꢀ8.524
ꢀ8.661
ꢀ7.908
ꢀ7.266
ꢀ7.333
ꢀ7.218
ꢀ7.154
ꢀ1.324
ꢀ1.302
ꢀ1.613
ꢀ1.211
ꢀ0.616
ꢀ0.269
ꢀ0.128
ꢀ0.408
ꢀ0.306
ꢀ0.334
ꢀ0.285
ꢀ0.473
ꢀ0.480
ꢀ0.391
F
H (1b)
ꢀ0.287
ꢀ0.210
ꢀ0.535
0.240
1.041
1.038
F
Br (1c)
F
Me2PhSi (1d)
MeO (1e)
F (1f)
1.054
F
1.043
H
H
0.423
ꢀ0.639
ꢀ0.610
H (1g)
ꢀ0.167
a
Computation was carried out by the Gaussian 09W (rev. D.01) software with the B3LYP/6-311 + + G** level of theory. Natural charge was obtained by the NBO analysis.
Table 2
Investigation of reaction conditions.
.
Entry
NuH
(Equiv)a
Base
(Equiv)a
Solvent
Temp. (8C)
Time (h)
Yieldb (%)
6
1
PhCH2OH
PhCH2NH2
PhSH
(0.83)
(0.83)
(0.83)
(0.83)
(0.83)
(0.83)
(0.83)
(0.83)
(0.83)
(0.83)
(0.83)
(0.83)
(1.5)
NaH
n-BuLi
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
(0.92)
(0.92)
(0.92)
(0.92)
(0.92)
(0.92)
(0.92)
(0.92)
(0.92)
(0.92)
(0.92)
(0.92)
(1.65)
(2.2)
THF
rt
0.5
c
2
THF
rt
0.5
–
c
3
THF
rt
0.5
–
c
4
CH2(CO2Et)2
PhOH
THF
rt
0.5
–
c
5
THF
rt
0.5
–
6
PhCH2OH
PhCH2OH
PhCH2OH
PhCH2OH
PhCH2OH
PhCH2OH
PhCH2OH
PhCH2OH
PhCH2OH
PhCH2OH
THF
rt
3
[6]
52
56
62
59
60
60
85
[99]
98
7
THF
60
rt
2
8
DMF
DMF
DMF
DMF
DMSO
DMF
DMF
DMF
2
9
rt
Overnight
10
11
12
13
14
15
60
100
60
rt
2
2
2
2
2
2
(2)
rt
(3)
(3.3)
rt
a
Based on the amount of 1a (1.0 equiv). Yields were calculated on the basis of NuH (Entries 1–12) and 1a (Entries 13–15).
Yields were determined by 19F NMR using PhCF3 as an internal standard, and in the brackets were shown the isolated yields. Yields were calculated on the base of the
b
amount of NuH (Entries 1–12) or 1a (Entries 13–15).
c
No reaction was observed.
example which actually experienced the addition–elimination
type substitution at the C2 site of 2,3,3,3-tetrafluoroprop-1-ene 1a
in spite of a rather low yield. MeMgBr and n-BuLi were employed as
a base instead of NaH in Entry 1, but the resultant metal alkoxides
did not work properly (not shown in the Table). Although
extension of the reaction period did not give any fruitful result
(Entries 6 vs 1), increase of the temperature to 60 8C affected the
reaction significantly to produce the desired product 2a in 52%
yield (Entry 7).
The same process under various conditions (solvents, temper-
ature, and time)clarified that irrespective of temperature and time,
constant formation of approximately 60% yield of 2a was observed
by employment of either DMF or DMSO as a solvent (Entries 8–12).
For obtaining better results, quantity of a nucleophile was
increased from 0.83 equiv to 3 equiv (Entries 8 and 13–15), and
eventually, the condition shown in Entry 14 was proved to be the
best among tested, realizing almost quantitative construction of
the desired addition–elimination product 2a.
Successful determination of the reaction conditions as above
allowed us to employ a variety of alcohols for clarification of scope
and limitation of the present process whose results were collected
in Table 3. Like the case of benzyl alcohol, 1- and 2-phenylethanols,
and 3-phenylprop-2-en-1-ol (cinnamyl alcohol) behaved in a
similar manner to furnish the corresponding products in more than
80% yields in every instance. Interesting to note is the case of Entry
4 whose product 2d with the allyl vinyl ether structure applicable
for Claisen rearrangement was successfully isolated because of
occurrence of this addition–elimination process only at room
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3
Table 3
Reaction of 1a with a variety of alkoxidesa.
.
Entry
R
(Equiv)b
Solvent
Product
Isolated yield (%)
1
PhCH2–
(2.0)
(2.0)
(2.0)
(2.0)
(2.0)
(2.0)
(2.0)
(2.0)
(3.0)
(3.0)
(3.0)
(1.0)
(0.25)e
(1.0)
(0.25)e
DMF
2a
99
81
87
81
98
99
38
2
PhCH(CH3)–
DMF
2b
3
PhCH2CH2–
DMF
2c
4
PhCH5CHCH2–
4-CH3O–C6H4–CH2–
4-H3C–C6H4–CH2–
4-Br–C6H4–CH2–
4-O2N–C6H4–CH2–
DMF
2d
5
DMF
2e
6
DMF
2f
7
DMF
2g
8
DMF
No reaction
9
n-C6H13
c-C6H11
4-t-Bu-c-C6H10
–
THF:DMF = 3:1
THF:DMF = 3:1
THF:DMF = 3:1
DMF
2h
36
44
60
89
91
42
74
(Quant)c
(87)c
(92)c
10
11
12
13
14
15
–
2i
–
2j
2-HOH2C–C6H4–CH2–
2-HOH2C–C6H4–CH2–
4-HOH2C–C6H4–CH2–
4-HOH2C–C6H4–CH2–
2kd
2lf
DMF
DMF
2mg
2mg
[48]h
[17]h
DMF
a
1.1 equiv of NaH to ROH was employed unless otherwise noted.
Equivalent was calculated on the basis of the amount of 1a.
The yields shown in the parenthesis were determined by 19F NMR.
b
c
d
e
f
Product 2k was obtained as the result of selective reaction at the only one of the two OH groups of the substrate.
4.4 equiv of NaH to ROH (2.2 equiv/OH) was employed and yields were calculated on the base of the amount of alcohols.
Product 2l was obtained as the result of selective reaction at the both OH groups of the substrate.
Product 2m was obtained as the result of selective reaction at the both OH groups of the substrate.
In the bracket was shown the recovery of 1,4-C6H4(CH2OH)2.
g
h
temperature. Attachment of a strong electron-withdrawing CF3
moiety would exceedingly improve the stability of 2d with the
inherently electron-rich vinyl ether part, which rendered chro-
matographic isolation possible.
or b in high yields when the reactions were conducted under reflux
in methanol or ethanol, respectively (Scheme 1). These products
can be recognized as the acetals from 1-bromo-3,3,3-trifluoroa-
cetone which were, different from the corresponding non-
fluorinated counterparts, not easily accessible from the parent
ketone. Thus, in spite of ready transformation to the corresponding
hemiacetals by attack of an alcohol molecule to the activated
carbonyl carbon by the strongly electron-withdrawing CF3 group,
this unique electronic effect significantly retards the elimination of
an OH group under the usual acidic conditions. Actually,
brominated acetals 3 were unprecedented thus far [8].
Another utilization of the addition–elimination product from
1a was exemplified by 2d which, as reported previously [9,10],
experienced facile [3,3] sigmatropic rearrangement. The desired
conversion proceeded just by stirring 2d in toluene at room
temperature, leading to formation of the ketone 4 in 61% isolated
yield (Scheme 2).
p-Substituted benzyl alcohols with electron-donating (Entries 5
and 6) as well as -withdrawing groups (Entries 7 and 8) were tested
in this transformation. Almost quantitative conversion was noticed
for alcohols with methoxy and methyl groups at the para position,
while only 38% yield was attained by 4-bromobenzyl alcohol and
the strongly electron-withdrawing 4-nitro substituent completely
inhibited the desired reaction which was apparently due to low
nucleophilicity of the resultant electron-deficient alkoxide. n- and
c-Hexanols were proved to similarly affect the present process
with recording excellent yields at the stage of completion of the
reaction, while ready loss of products was noticed during workup
and chromatographic purification processes due to their relatively
high volatility, and close boiling points of products and the excess
substrate alcohols rendered their separation by distillation difficult
(Entries 9 and 10). This problem was slightly improved by
employment of tert-Bu-possessing cyclohexanol with higher
boiling point (Entry 11). In these cases, the mixed solvent system
of THF:DMF = 3:1 was required because the corresponding alk-
oxides were insoluble in DMF while this solvent albeit in a small
portion was important for attainment of better chemical yields.
Interesting observation was encountered in the case of
benzenedimethanols as substrates. Thus, as our expectation,
mono- and disubstitution products 2k and l were selectively
prepared in excellent yields just by control of the amount of 1,2-
benzenedimethanol added, while this was not the case for the
corresponding 1,4-dimethanol, leading to formation of disubsti-
tuted product 2m irrespective of the equivalent of the nucleophile.
The reason on this clear difference was not clear at present.
CF3-containing vinyl ethers 2 thus obtained were found to
possess enough reactivity toward such an electrophile as
N-bromosuccinimide (NBS), affording the addition products 3a
Scheme 1. Conversion of 2 to bromotrifluoroacetone acetals.
Scheme 2. Claisen rearrangement of 2d.
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3. Conclusion
(4.86 mmol) of 2b as
a
yellow oil in 81% yield. Rf = 0.60
1.59 (3H, d, J = 6.0 Hz), 4.24
(1H, qd, J = 1.9, 3.9 Hz), 4.74 (1H, d, J = 4.2 Hz), 5.08 (1H, q,
J = 6.5 Hz), 7.25–7.39 (5H, m). 13C NMR
23.9, 76.9, 89.6 (q,
J = 3.7 Hz), 123.4 (q, J = 267.7 Hz), 125.8, 127.8, 128.7, 141.4, 148.6
(q, J = 34.1 Hz). 19F NMR
ꢀ74.12 (s). IR (neat) 3067, 3033, 2935,
1656, 1604, 1385, 1348, 1284, 1161, 1029 cmꢀ1. Anal. Calcd for
11H11F3O: C, 61.11; H, 5.13. Found: C, 60.66; H, 5.11.
(hexane:AcOEt = 3:1). 1H NMR
d
As shown above, we have clarified the unique reactivity of
2,3,3,3-tetrafluoroprop-1-ene 1a toward nucleophiles, and found
out that this fluorinated olefin 1a smoothly and regiospecifically
reacted with alkoxides to furnish the corresponding substitution
products 2 as a result of addition–elimination sequence at the 2
position. 2 was also proved to experience bromonium ion addition
in an alcoholic solvent, leading to successful formation of hitherto
unknown acetals which is difficult to be accessible from the parent
1-bromo-3,3,3-trifluoroacetone due to the electroninc effect of the
CF3 group.
d
d
n
C
4.2.3. 3,3,3-Trifluoro-2-[(2-phenylethyl)oxy]prop-1-ene (2c)
1.466 g (12.0 mmol) of 2-phenylethanol was employed instead
of benzyl alcohol, and the same procedure afforded 1.129 g
(5.22 mmol) of 2c as
(hexane:AcOEt = 3:1). 1H NMR
t, J = 7.1 Hz), 4.39 (1H, qd, J = 1.9, 4.2 Hz), 4.79 (1H, d, J = 4.2 Hz),
7.21–7.35 (5H, m). 13C NMR
36.0, 69.3, 87.1 (q, J = 3.5 Hz), 119.7
(q, J = 272.9 Hz), 121.2, 128.3, 128.4, 137.4, 150.2 (q, J = 34.4 Hz).
a
yellow oil in 87% yield. Rf = 0.71
4. Experimental
d
3.06 (2H, t, J = 7.1 Hz), 3.97 (2H,
4.1. General
d
All reactions were carried out under an argon atmosphere in
dried glassware with magnetic stirring. Anhydrous THF and CH2Cl2
were purchased and were used without further purification. DMF
was used after distillation in the presence of NaH. Spherical neutral
19F NMR
d
ꢀ73.78 (s). IR (neat)
n 3066, 3032, 2928, 2856, 1657,
1604, 1349, 1297, 1161, 1030 cmꢀ1. HRMS-FAB (m/z): [M]+ calcd.
for C11H11F3O, 216.0762; found, 216.0726.
silica gel (63–210
m
m) was employed for column chromatography.
4.2.4. 3,3,3-Trifluoro-2-[(E)-(3-phenylprop-2-en-1-yl)oxy]prop-1-
ene (2d) [9]
1.55 mL (12.0 mmol) of (E)-3-phenylprop-2-en-1-ol was
employed instead of benzyl alcohol, and the same procedure
afforded 1.102 g (4.83 mmol) of 2d as a yellow oil in 81% yield.
Rf = 0.57 (hexane:AcOEt = 3:1). 1H NMR
d 4.50 (1H, qd, J = 1.8,
1H (300.40 MHz), 13C (75.45 Hz), and 19F (282.65 Hz) NMR spectra
were recorded in CDCl3 and chemical shifts were recorded in parts
per million (ppm), downfield from internal tetramethylsilane
(Me4Si:
d d
0.00, for 1H and 13C) or hexafluorobenzene (C6F6:
ꢀ163.00 for 19F). Data were tabulated in the following order:
number of protons, multiplicity (s, singlet; d, doublet; t, triplet; q,
quartet; m, multiplet; b, broad peak), coupling constants in Hertz.
Infrared (IR) spectra were reported in wave numbers (cmꢀ1). High
resolution mass spectra were taken on a JEOL JMS-700 MS
spectrometer and reported in wave numbers (cmꢀ1). Elemental
analyses were conducted on a PerkinElmer2400 Series II CHNS/O
System.
3.6 Hz), 4.52 (2H, dd, J = 1.4, 5.9 Hz), 4.87 (1H, d, J = 4.2 Hz), 6.32
(1H, td, J = 5.9, 16.2 Hz), 6.69 (1H, brd, J = 15.9 Hz), 7.25–7.37 (5H,
m). 13C NMR
d
69.2, 87.9 (q, J = 3.7 Hz), 119.8 (q, J = 272.0 Hz),
126.6, 127.1, 127.3, 127.4, 128.6, 133.9, 150.0 (q, J = 34.5 Hz). 19F
NMR
ꢀ73.77 (s).
d
4.2.5. 3,3,3-Trifluoro-2-[(4-methoxybenzyl)oxy]prop-1-ene (2e)
1.658 g (12.0 mmol) of 4-methoxybenzyl alcohol was
employed instead of benzyl alcohol, and the same procedure
afforded 1.393 g (6.00 mmol) of 2e as a colorless oil in quantitative
4.2. General procedure for the preparation of 2
4.2.1. 2-(Benzyloxy)-3,3,3-trifluoroprop-1-ene (2a)
yield. Rf = 0.71 (Hexane:AcOEt = 3:1). 1H NMR
(1H, qd, J = 1.9, 3.9 Hz), 4.81 (2H, s), 4.86 (1H, d, J = 3.9 Hz), 6.89–
6.93 (2H, m), 7.27–7.31 (2H, m). 13C NMR
55.2, 70.3, 88.0 (q,
J = 3.7 Hz), 114.0, 119.8 (q, J = 272.7 Hz), 127.3, 129.2, 150.1 (q,
d 3.81 (3H, s), 4.50
To a two-necked flask containing 0.576 g of NaH (55% in
paraffin, 13.2 mmol) in 15 mL of DMF under an argon atmosphere
at 0 8C was slowly added 1.24 mL of benzyl alcohol (12.0 mmol).
After 30 min stirring at this temperature, the resultant alkoxide
solution was transferred to a pressure tight reactor with 50 mL
capacity where 2,3,3,3-tetrafluoroprop-1-ene (HFO-1234yf, 1a)
was introduced at room temperature so as to set the inside
pressure as 0.3 MPa after evacuation at ꢀ100 8C. This method
allowed to add approximately 6 mmol of 1a. After stirring for 2 h at
room temperature, the crude reaction mixture was poured into a
saturated aqueous solution of NH4Cl (20 mL) and acidified to ca.
pH = 6 by 1 M aqueous HCl, and the resultant solution was
extracted three times with Et2O. The combined ethereal layer was
dried over anhydrous Na2SO4, and removal of the desiccant by
filtration and concentration furnished a crude material, which was
d
J = 34.5 Hz), 159.7. 19F NMR
d
ꢀ73.73 (s). IR (neat)
n 3007, 2939,
1654, 1615, 1587, 1396, 1303, 1029 cmꢀ1. HRMS (ESIꢀ, m/z):
[MꢀH]ꢀ calcd for C11H10F3O2, 231.0631; Found, 231.0636.
4.2.6. 3,3,3-Trifluoro-2-[(4-methylbenzyl)oxy]prop-1-ene (2f)
1.466 g (12.0 mmol) of 4-methylbenzyl alcohol was employed
instead of benzyl alcohol, and the same procedure afforded 1.277 g
(5.91 mmol) of 2f as a colorless oil in 99% yield. Rf = 0.74
(hexane:AcOEt = 3:1). 1H NMR
J = 1.8, 4.2 Hz), 4.84 (2H, s), 4.85 (1H, d, J = 3.9 Hz), 7.17–7.25
(4H, m). 13C NMR
21.1, 70.5, 88.1 (q, J = 3.5 Hz), 119.8 (q,
J = 272.9 Hz), 127.5, 129.3, 132.2, 138.2, 150.2 (q, J = 34.5 Hz). 19F
d 2.36 (3H, s), 4.51 (1H, qd,
d
chromatographed on silica gel using
ne:Et2O = 10:1 as an eluent to afford 1.210 g (5.99 mmol) of 2a
in quantitative yield. Rf = 0.63 (hexane:AcOEt = 3:1). 1H NMR
4.51 (1H, qd, J = 1.8, 3.9 Hz), 4.61 (1H, d, J = 4.2 Hz), 4.89 (2H, s),
7.25–7.37 (5H, m). 13C NMR
70.4, 88.2 (q, J = 3.6 Hz), 119.8 (q,
J = 272.9 Hz), 127.3, 127.8, 128.6, 138.0, 150.0 (q, J = 34.5 Hz). 19F
a
solution of hexa-
NMR
d
ꢀ73.70 (s). IR (neat)
n 3030, 2926, 2881, 1656, 1519, 1395,
1019 cmꢀ1. HRMS (ESIꢀ, m/z): [MꢀH]– calcd for C11H10F3O,
d
215.0682; Found, 215.0686.
d
4.2.7. 2-[(4-Bromobenzyl)oxy]-3,3,3-trifluoroprop-1-ene (2g)
0.748 g (4.0 mmol) of 4-bromobenzyl alcohol and 0.192 g (55%,
4.4 mmol) of NaH were employed for the reaction with HFO-
1234yf (0.1 MPa, ca. 2 mmol), and the same procedure afforded
0.213 g (0.75 mmol) of 2g as a colorless oil in 38% yield. Rf = 0.57
NMR
d
ꢀ73.78 (s). IR (neat)
n 3067, 3034, 2927, 1658, 1348, 1193,
1160, 1026 cmꢀ1. Anal. Calcd for C10H9F3O: C, 59.41; H, 4.49.
Found: C, 59.44; H, 4.44.
(hexane:AcOEt = 3:1). 1H NMR
(2H, s), 4.89 (1H, d, J = 3.6 Hz), 7.23–7.25 (2H, m), 7.49–7.53 (2H,
m). 13C NMR
69.1, 88.4 (q, J = 3.7 Hz), 119.7 (q, J = 272.7 Hz),
122.2, 128.8, 131.7, 134.2, 149.8 (q, J = 34.7 Hz). 19F NMR
–73.28
d 4.45 (1H, qd, J = 2.0, 4.4 Hz), 4.84
4.2.2. 3,3,3-Trifluoro-2-[(1-phenylethyl)oxy]prop-1-ene (2b)
1.466 g (12.0 mmol) of 1-phenylethanol was employed instead
of benzyl alcohol, and the same procedure afforded 1.051 g
d
d
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5
(s). IR (neat)
n
3031, 2933, 1658, 1596, 1464, 1396, 1304, 1158,
3035, 2937, 1659, 1347, 1196, 1157, 1022 cmꢀ1. Anal. Calcd for
C14H12F6O2: C, 51.54; H, 3.71. Found: C, 51.59; H, 3.79.
1072 cmꢀ1. Anal. Calcd for C10H8BrF3O: C, 42.73; H, 2.87. Found: C,
43.05; H, 3.07.
4.2.13. 1,4-Bis[(3,3,3-trifluoroprop-1-en-2-yl)oxymethyl]benzene
(2m)
4.2.8. 2-(Hexyloxy)-3,3,3-trifluoroprop-1-ene (2h)
1.50 mL (12.0 mmol) of n-hexanol in a mixed solvent of DMF
(15 mL) and THF (5 mL) was reacted with HFO-1234yf under
0.2 MPa pressure (ca. 4 mmol), and the same procedure afforded
0.353 g (1.80 mmol) of 2 h as a colorless oil in 45% yield. Rf = 0.89
0.207 g (1.5 mmol) of 1,2-benzenedimethanol and 0.288 g (55%,
6.6 mmol) of NaH were employed, and the same procedure
afforded 0.362 g (1.11 mmol) of 2m as a colorless oil in 74% yield.
Rf = 0.54 (hexane:AcOEt = 3:1). mp. 52.4 8C. 1H NMR
d
4.51 (2H, qd,
J = 1.8, 4.2 Hz), 4.89 (2H, d, J = 4.2 Hz), 4.90 (4H, s), 7.26–7.39 (4H,
m). 13C NMR
70.1, 88.3 (q, J = 3.5 Hz), 119.8 (q, J = 272.9 Hz),
127.6, 135.4, 150.0 (q, J = 34.7 Hz).19 F NMR
(hexane:AcOEt = 3:1). 1H NMR
J = 6.6 Hz), 4.51 (1H, qd, J = 1.8, 4.2 Hz), 4.76 (1H, d, J = 3.6 Hz). 13
NMR 13.9, 22.5, 25.5, 28.4, 31.4, 68.8, 86.7 (q, J = 3.5 Hz), 119.9 (q,
J = 273.3 Hz), 150.6 (q, J = 34.3 Hz). 19F NMR
d 0.90–1.74 (11H, m), 3.78 (2H, t,
C
d
d
d –73.72 (s). IR (KBr) n
d
ꢀ74.10 (s). IR (neat)
n
3074, 3041, 2933, 1659, 1347, 1196, 1157, 1022 cmꢀ1. Anal. Calcd
for C14H12F6O2: C, 51.54; H, 3.71. Found: C, 51.65; H, 3.60.
2934, 2861, 2357, 1654, 1468, 1396, 1348, 1265, 1163 cmꢀ1. HRMS
(ESI+, m/z): [M + H]+ calcd for C9H16F3O, 197.1153; Found,
197.0787.
4.3. General procedure for the preparation of 3a
4.2.9. 2-(Cyclohexyloxy)-3,3,3-trifluoroprop-1-ene (2i)
4.3.1. 2-(Benzyloxy)-3-bromo-1,1,1-trifluoro-2-methoxypropane
(3a)
1.28 mL (12.0 mmol) of c-hexanol was used instead of n-
hexanol in 4.2.8, and the same procedure afforded 0.344 g
(1.77 mmol) of 2i as a colorless oil in 44% yield. Rf = 0.91
A methanol solution (18 mL) containing N-bromosuccinimide
(0.392 g, 2.20 mmol) and 2-benzyloxy-3,3,3-trifluoroprop-1-ene
(0.202 g, 1.00 mmol) was refluxed for 3 h under an argon
atmosphere. After evaporation of the solvent, the resultant white
solid was successively washed with H2O and Et2O, and the
obtained liquid was extracted with Et2O three times. The combined
ethereal layer was dried over anhydrous Na2SO4 and removal of
the desiccant by filtration and concentration furnished a crude
material, which was chromatographed on silica gel using a solution
of hexane:Et2O = 10:1 as an eluent to afford 0.274 g (0.878 mmol)
(hexane:AcOEt = 3:1). 1H NMR
d
1.34–1.45 (6H, m), 1.76–1.91
(4H, m), 4.05 (1H, m), 4.51 (1H, qd, J = 1.7, 3.7 Hz), 4.76 (1H, d,
J = 3.6 Hz). 13C NMR
23.3, 25.5, 30.6, 76.2, 87.4 (q, J = 3.7 Hz),
120.2 (q, J = 253.5 Hz), 148.8 (q, J = 33.9 Hz). 19F NMR
ꢀ74.21 (s).
IR (neat) 2941, 2861, 2367, 1649, 1451, 1387, 1344, 1265, 1160,
1045 cmꢀ1 HRMS (ESI+, m/z): [M + H]+ calcd for C9H14F3O,
d
d
n
.
195.0997; Found, 195.0993.
4.2.10. 2-[(4-tert-Butylcyclohexyl)oxy]-3,3,3-trifluoroprop-1-ene
(2j)
1.875 g (12.0 mmol) of 4-tert-butylcyclohexanol was used
instead of n-hexanol in 4.2.8, and the same procedure afforded
0.599 g (2.39 mmol) of 2j as a colorless oil in 60% yield. Rf = 0.94
of 3a in 88% yield. Rf = 0.71 (hexane:AcOEt = 3:1). 1H NMR
(3H, s), 3.63 (2H, s), 4.68 (1H, d, J = 11.3 Hz), 4.79 (1H, d, J = 11.1 Hz),
7.31–7.39 (5H, m). 13C NMR
27.8, 51.2 (q, J = 1.3 Hz), 65.3 (q,
J = 1.6 Hz), 97.1 (q, J = 29.8 Hz), 120.4 (q, J = 291.8 Hz), 127.4, 127.6,
d 3.50
d
128.5, 136.6. 19F NMR
3092, 3066, 3034,
2985, 2954, 1608, 1498, 1345, 1029 cmꢀ1
. Anal. Calcd for
d
ꢀ77.08 (s). IR (neat)
n
(hexane:AcOEt = 3:1). 1H NMR
d
0.86 (9H, s), 1.06–1.37 (5H, m),
1.85–2.15 (4H, m), 3.98 (1H, m), 4.41 (1H, qd, J = 1.7, 3.8 Hz), 4.81
(1H, d, J = 3.6 Hz). 13C NMR
21.2, 25.4, 27.6, 31.3, 47.5, 72.5, 87.4
(q, J = 3.3 Hz), 120.0 (q, J = 274.2 Hz), 149.0 (q, J = 33.7 Hz). 19F NMR
C11H12BrF3O: C, 42.20; H, 3.86. Found: C, 42.49; H, 3.90.
d
4.3.2. 2-Benzyloxy-3-bromo-2-ethoxy-1,1,1-trifluoropropane (3b)
By using the same amount of ethanol instead of methanol,
0.2807 g (0.858 mmol) of 3b was obtained in 86% yield. Rf = 0.74
d
ꢀ73.92 (s). IR (neat)
n 2950, 2868, 2357, 1650, 1479, 1389, 1350,
1284, 1049, 1028 cmꢀ1. Anal. Calcd for C13H21F3O: C, 62.38; H,
8.46. Found: C, 62.29; H, 8.35.
(hexane:AcOEt = 3:1). 1H NMR
d
1.28 (3H, t, J = 7.1 Hz), 3.64 (2H, s),
3.73 (1H, m), 3.82 (1H, qd, J = 7.2, 9.3 Hz), 4.68 (1H, d, J = 11.4 Hz),
4.80 (1H, d, J = 11.4 Hz), 7.29–7.38 (5H, m). 13C NMR
14.7, 27.3,
59.3 (q, J = 1.4 Hz), 65.0 (q, J = 1.6 Hz), 96.9 (q, J = 28.3 Hz), 120.4 (q,
J = 292.2 Hz), 126.7, 127.6, 128.6, 136.7. 19F NMR
ꢀ77.34 (s). IR
4.2.11. 2-[(3,3,3-Trifluoroprop-1-en-2-yl)oxymethyl]benzyl alcohol
(2k)
0.276 g (2.0 mmol) of 1,2-benzenedimethanol and 0.096 g (55%,
2.2 mmol) of NaH were employed for the reaction with HFO-
1234yf (0.1 MPa, ca. 2 mmol), and the same procedure afforded
0.413 g (1.78 mmol) of 2k as a colorless oil in 89% yield. Rf = 0.30
d
d
(neat)
n 3066, 3034, 2983, 2935, 2904, 1610, 1498, 1344,
1029 cmꢀ1. HRMS (ESI+, m/z): [M + Na]+ calcd for C12H14BrF3O2Na,
349.0027; Found, 349.0047.
(hexane:AcOEt = 3:1). 1H NMR
3.8 Hz), 4.73 (2H, s), 4.92 (1H, d, J = 3.9 Hz), 4.99 (2H, s), 7.32–7.46
(4H, m). 13C NMR
62.7, 68.7, 88.4 (q, J = 3.7 Hz), 119.8 (q,
J = 273.0 Hz), 128.0, 128.6, 128.9, 129.0, 133.0, 139.1, 149.9 (q,
d 1.88 (1H, br), 4.62 (1H, qd, J = 1.9,
4.4. Preparation of 1,1,1-trifluoro-4-phenylhex-5-en-2-one (4) [10]
d
0.114 g (0.50 mmol) of 3,3,3-trifluoro-2-[(E)-(3-phenylprop-2-
en-1-yl)oxy]prop-1-ene in CH2Cl2 (5 mL) was added at 0 8C under
an argon atmosphere 0.12 mL (1.0 mmol) of BF3ꢁOEt2 and stirring
was continued for 30 min at this temperature. After addition of
H2O (5 mL), extraction with CH2Cl2, drying with anhydrous
Na2SO4, and concentration furnished a crude material, which
was chromatographed on silica gel using a solution of hexane:A-
cOEt = 8:1 as an eluent to afford 0.070 g (0.306 mmol) of 4a in
J = 35.1 Hz). 19F NMR
2930, 1608, 1455, 1291, 1161, 1029 cmꢀ1
d
ꢀ73.52 (s). IR (neat)
n
3339, 3073, 3031,
Anal. Calcd for
.
C11H11F3O2: C, 56.90; H, 4.77. Found: C, 56.98; H, 4.95.
4.2.12. 1,2-Bis[(3,3,3-trifluoroprop-1-en-2-yl)oxymethyl]benzene
(2l)
0.207 g (1.5 mmol) of 1,2-benzenedimethanol and 0.288 g (55%,
6.6 mmol) of NaH were employed, and the same procedure
afforded 0.447 g (1.37 mmol) of 2l as a colorless oil in 91% yield.
61%yield. Rf = 0.62 (hexane:AcOEt = 3:1). 1H NMR
d 3.11 (1H, dd,
J = 6.6, 18.0 Hz), 3.20 (1H, dd, J = 7.5, 18.0 Hz), 4.01 (1H, q,
J = 7.2 Hz), 5.07 (1H, td, J = 1.2, 17.1 Hz), 5.12 (1H, td, J = 1.2,
10.5 Hz), 5.96 (1H, ddd, J = 6.6, 10.2, 16.8 Hz), 7.25–7.37 (5H, m).
Rf = 0.66 (hexane:AcOEt = 3:1). 1H NMR
d
4.51 (2H, qd, J = 1.8,
3.9 Hz), 4.61 (2H, d, J = 4.2 Hz), 4.89 (4H, s), 7.25–7.37 (4H, m). 13
NMR 68.7, 88.4 (q, J = 3.5 Hz), 119.8 (q, J = 272.9 Hz), 129.0, 129.1,
133.1, 149.9 (q, J = 34.7 Hz). 19F NMR
ꢀ73.64 (s). IR (neat) 3073,
C
d
13C NMR
128.8, 139.1, 141.4, 189.4 (q, J = 35.2 Hz). 19F NMR
d
d
41.7, 43.1, 115.4 (q, J = 292.3 Hz), 115.5, 127.0, 127.4,
ꢀ80.83 (s).
d
n
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J.M. Millam, M. Klene, J.E. Knox, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R.
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Please cite this article in press as: Y. Hiraoka, et al., J. Fluorine Chem. (2015), http://dx.doi.org/10.1016/j.jfluchem.2015.05.006