CFC- or HFC-free approach to α-substituted β,γ,γ-trifluoroallyl alcohols by the reaction of β-fluoro-β-trifluoromethylated enol tosylate with Grignard reagents

Article abstract of DOI:10.1055/s-2002-32607

The reaction of β-fluoro-β-trifluoromethylated enol tosylate with Grignard reagents giving the corresponding β,γ,γ-trifluoroallyl alcohols as well as heteropoly acid-mediated ethanolysis of the allyl alcohols affording (Z)-β-substituted α-fluoro-α,β-unsaturated esters is described.

Full text of DOI:10.1055/s-2002-32607

1134
LETTER
CFC- or HFC-Free Approach to -Substituted , , -Trifluoroallyl Alcohols by
the Reaction of -Fluoro- -trifluoromethylated Enol Tosylate with Grignard
Reagents
C
FC
-
or
H
FC-Free
a
A
pproach
z
to Trifluoro
u
allyl
A
lcoho
m
ls asa Funabiki,*a Ken-ichi Sawa,b Katsuyoshi Shibata,b Masaki Matsui*a
a
Department of Materials Science and Technology, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan
b
Department of Chemistry, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan
Fax +81(58)2301893; E-mail: kfunabik@apchem.gifu-u.ac.jp
Received 15 April 2002
We report here a new expedient entry to -substituted
, , -trifluoroallyl alcohols using the reaction of -fluo-
ro- -trifluoromethylated enol tosylate,7 readily prepared
from commercially available polyfluoroalcohol, with
Grignard reagents (Scheme 2).
Abstract: The reaction of -fluoro- -trifluoromethylated enol to-
sylate with Grignard reagents giving the corresponding , , -tri-
fluoroallyl alcohols as well as heteropoly acid-mediated ethanolysis
of the allyl alcohols affording (Z)- -substituted -fluoro- , -un-
saturated esters is described.
Key words: fluorine, trifluoromethyl, Grignard reaction, sul-
fonates, cleavage, nucleophilic additions, alcohols, esters
Grignard
reagents
OH
F3C
F
H
CF3CF2CH2OH
F2C
R
OTs
F
Trifluoroallyl alcohols are one of the most useful interme-
diate in organofluorine chemistry.1 Although there are
several accesses to these compounds, previous methods
suffer from the use of chlorofluorocarbon (CFC)2 or
bromofluorocarbon3 as starting substrates, which will not
be able to be used in the future according to the protocol
of Montreaol. Fluoroalkylsilanes are also usable for the
synthesis of title products. But bromofluoroalkylcarbons
are essential for the preparations of the silanes.4 Recently,
Burdon had found that 1,1,1,2-tetrafluoroethane (HFC-
134a) can be employed as a precursor of tetrafluorovinyl-
lithium spieces,5 and Burdon and Percy have extended its
synthetic utilizations for the synthesis of aliphatic orga-
nofluorine compounds (Scheme 1).6
Scheme 2
-fluoro- -trifluoromethylated enol tosylate can be pre-
pared according to the our previous report.7c
To a THF solution of phenylmagnesium bromide (PhMg-
Br) (1.05 M THF solution, 2.9 mL, 3 mmol) was slowly
added a THF (1 mL) solution of 3,3,3,4-tetrafluoro-1-pro-
penyl tosylate (1) (1 mmol) at ambient temperature under
argon. After being stirred at reflux temperature for 3 h, the
reaction mixture was quenched with a cold saturated
NH4Cl solution (50 mL), followed by extraction with di-
ethyl ether (30 mL 3). The oraganic layer was washed
with a NaHCO3 solution (20 mL 2) and brine (20 mL
2), dried over Na2SO4, and concentrated in vacuo to give
the residue, which was chromatographed on silica gel us-
ing chloroform to obtain the corresponding 2,3,3-trifluo-
ro-1-phenyl-2-propen-1-ol (2a) in 75% yield (Table 1,
entry 3). Conducting the reaction at 50 °C or at room tem-
perature provided the less yield of 2a with recovery of 1a
(entries 1 and 2). Two equivalents of PhMgBr was not
enough to obtain good yield of 2a (entry 4).
Met
RMet
BuLi
RfCl or RfBr
CF3CFH2F
HFC-134a
F2C
F
R'CHO
OH
RCHO
RfSi
F2C
R'
Other Grignard reagents carrying 4-methylphenyl, 4-
chlorophenyl, or 2-napthyl group, participated well in the
Si = R3Si
F
Scheme 1 Previous Methods for the Preparations of -Substituted reaction to give the corresponding , , -trifluoroallyl al-
, , -Trifluoroallyl Alcohols
cohols 2b–d in 57–80% yields (entries 5–8). However the
reaction of 1 with 2-methyphenylmagnesium bromide
was very sluggish to give the corresponding allyl alcohol
2e in only 25% yield, due to the steric factor of the methyl
group at 2-position on the phenyl group (entry 9). The re-
action with hydrocinnamylmagnesium bromide also did
not proceed effectively, producing the corresponding al-
cohol 2f in only 14% yield (entry 10).
However low boiling point (-26.5 °C) of HFC-134a seems
to cause handling problem at ambient temperature. There-
fore, more convenient and CFC- or HFC-free approaches
to these compounds are still required.
Synlett 2002, No. 7, 01 07 2002. Article Identifier:
1437-2096,E;2002,0,07,1134,1136,ftx,en;Y05802ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
CFC- or HFC-Free Approach to Trifluoroallyl Alcohols
1135
Although the optimization of the ethanolysis conditions
was not carried out, some results can be described. Using
a catalytic or small amount of tungstosilicic acid
(H4SiW12O40)10 (0.2–1.0 g/1 mmol of 2), which has re-
markable advantages such as ease of handle and non-cor-
rosiveness, at reflux temperature afforded (Z)- -fluoro-
, -unsaturated carboxylic acid esters 3a,b exclusively in
good yields, (entries 2–5). The ethanolysis at room tem-
perature did not occur, the alcohol 2a being recovered in
quantitative yield (entry 4). Montmorillonite K 10 (Clay,
MK10) is not effective for the ethanolysis of the allyl al-
cohol 2a (Table 2, entry 1) at all.11 It should be noted that
only (Z)-isomer was obtained in the all cases.
Table 1 Preparation of -Substituted , , -Trifluroallyl Alcohol 2
OH
F3C
F
H
F2C
+
RMgBr
THF
R
OTs
F
1
2
Entrya RMgBr (equiv)
Temp.
Product Yield (%)b
1
2
PhMgBr (3)
r.t.
2a
2a
2a
2a
2b
2c
2c
2d
2e
2f
53 (10)
71 (6)
75c
PhMgBr (3)
50 °C
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
3
PhMgBr (3)
4
PhMgBr (2)
59 (12)
85c
In short, we describe herein the first reaction of -fluoro-
-trifluoromethylated enol tosylate with Grignard re-
agents providing a new entry to -substituted , , -triflu-
oroallyl alcohols as well as H4SiW12O40-mediated
ethanolysis of the alcohols affording (Z)- -substituted -
fluoro- , -unsaturated carboxylic acid esters 3, exclu-
sively.
5
4-MeC6H4MgBr (3)
4-ClC6H4MgBr (3)
4-ClC6H4MgBr (5)
2-NapMgBr (3)
2-MeC6H4MgBr (5)
6
57c
7
72c
8
70c
9
25 (trace)
14 (trace)
References
10
PhCH2CH2MgBr (5)
(1) For recent examples, see: (a) Takagi, Y.; Nakatani, T.; Itoh,
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(c) Peng, S.; Qing, F.-L. J. Chem. Soc., Perkin Trans. 1
1999, 3345. (d) Fujita, M.; Hiyama, T. Tetrahedron Lett.
1986, 27, 3659.
a The reaction was performed with tosylate 1 (1 mmol) in THF
(4 mL).
b 19F NMR yields. Values in parentheses stand for the recovery of 1.
c Yields of isolated products.
(2) (a) Gillet, J. P.; Sauvêtre, R.; Normant, J. F. Synthesis 1986,
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As described in Table 2, moreover, -substituted , , -
trifluoroallyl alcohols 2 can be converted to the corre-
sponding -substituted -fluoro- , -unsaturated carboxy-
lic acid esters 3 without the use of an excess amount of
concd H2SO48 or iodine.9
Table 2 Preparation of (Z)- -Substituted -Fluoro- , -unsaturated
Carboxylic Acid Esters 3
O
OH
Solid Acid
EtOH, 1 h
F2C
EtO
R
R
F
F
3
2
Entrya
R
Solic Acid
(g/mmol of 2)
Temp. Product Yield
(%)b
1
2
3
4
5
Ph
Ph
Ph
Ph
M K10 (0.2)
reflux 3a
7 (70)
H4SiW12O40 (0.2) reflux 3a
H4SiW12O40 (1.0) reflux 3a
69 (18)
85
(7) For the reaction of -fluoro- -difluoromethylated alkenyl
tosylates toward various fluorinated molecules, see:
(a) Funabiki, K.; Fukushima, Y.; Sugiyama, T.; Shibata, K.;
Matsui, M. Synlett 2001, 1308. (b) Funabiki, K.;
H4SiW12O40 (1.0) r.t.
3a
0 (95)
87
Fukushima, Y.; Matsui, M.; Shibata, K. J. Org. Chem. 2000,
65, 606. (c) Funabiki, K.; Ohtsuki, T.; Ishihara, T.;
Yamanaka, H. J. Chem. Soc., Perkin Trans. 1 1998, 2413.
(d) Funabiki, K.; Fukushima, Y.; Inagaki, T.; Murata, E.;
Matsui, M.; Shibata, K. Tetrahedron Lett. 1998, 39, 1913.
(e) Funabiki, K.; Suzuki, C.; Takamoto, S.; Matsui, M.;
4-MeC6H4 H4SiW12O40 (1.0) reflux 3b
a The reaction was performed with alcohol 2 (1 mmol) in EtOH (4 mL)
for 1 h.
b Yields of isolated products. Values in parentheses stand for the
recovery of 2.
Synlett 2002, No. 7, 1134–1136 ISSN 0936-5214 © Thieme Stuttgart · New York

1136
K. Funabiki et al.
LETTER
(9) For the iodine-catalyzed rearrangement of -fluoroallyl
Shibata, K. J. Chem. Soc., Perkin Trans. 1 1997, 2679.
(f) Funabiki, K.; Kurita, T.; Matsui, M.; Shibata, K. Chem.
Lett. 1997, 2679. (g) Funabiki, K.; Ohtake, C.; Muramatsu,
H.; Matsui, M.; Shibata, K. Synlett 1996, 444. (h) Funabiki,
K.; Ohtsuki, T.; Ishihara, T.; Yamanaka, H. Chem. Lett.
1996, 5. (i) Funabiki, K.; Ohtsuki, T.; Ishihara, T.;
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(10) H4SiW12O40 was purchased from Merck KGaA and dried at
room temperature (1 mmHg) for 2 h before using: (a) For a
recent example dealing with stereoselective synthesis, see:
Toshima, T.; Nagai, H.; Matsumura, S. Synlett 1999, 1420.
(b) For reviews on heteropoly acids, see: Kozhevnikov, I. V.
Chem. Rev. 1998, 98, 171. (c) Also see: Mizuno, N.;
Misono, M. Chem. Rev. 1998, 98, 199.
(8) For selected examples for the solvolysis of , -difluoro- or
-fluoroallyl alcohols derivatives, see: Tellier, F.; Sauvêtre,
R. Tetrahedron Lett. 1993, 34, 5433; and ref.2b.
(11) Funabiki, K.; Murata, E.; Fukushima, Y.; Matsui, M.;
Shibata, K. Tetrahedron 1999, 55, 4637.
Synlett 2002, No. 7, 1134–1136 ISSN 0936-5214 © Thieme Stuttgart · New York