Ring-opening fluorination of epoxides using hydrofluoric acid and additives

Article abstract of DOI:10.1016/S0022-1139(99)00180-3

Epoxides underwent ring-opening fluorination reaction with hydrofluoric acid in the presence of silicon fluorides and additives to give fluorohydrines in good yields.

Full text of DOI:10.1016/S0022-1139(99)00180-3

Journal of Fluorine Chemistry 99 (1999) 95±97
Ring-opening ¯uorination of epoxides using
hydro¯uoric acid and additives
Makoto Shimizua,*, Yuko Nakaharab
aDepartment of Chemistry for Materials, Mie University, Tsu, Mie 514-8507, Japan
bInstitute of Physical and Chemical Research (Riken), Wako, Saitama 351-0198, Japan
Received 28 April 1999; received in revised form 23 June 1999; accepted 23 July 1999
Abstract
Epoxides underwent ring-opening ¯uorination reaction with hydro¯uoric acid in the presence of silicon ¯uorides and additives to give
¯uorohydrines in good yields. # 1999 Elsevier Science S.A. All rights reserved.
Keywords: Epoxide; Hydro¯uoric acid; Fluorohydrin; Silicon tetra¯uoride
1. Introduction
for the opening of epoxides and halo¯uorination of ole®ns.
In the present paper a convenient procedure for the ring-
opening ¯uorination of epoxides using hydro¯uoric acid is
described.
Although hydro¯uoric acid is an inexpensive and readily
available reagent, its use as a ¯uorinating reagent has been
limited due to the low nucleophilicity of the ¯uoride ion [1±
3]. Intermolecular strong hydrogen bonding usually
diminishes the ability for ¯uorination, and the incorporation
of the existing water often induces formation of undesired
by-products [4]. For circumvention of above drawbacks,
anhydrous hydrogen ¯uoride±amine complexes have been
used successfully for a number of ¯uorination reactions
[1,5,6]. Among anhydrous hydrogen ¯uoride±amine com-
plexes, (iPr)2NHÁ3HF has been reported to effect the ring-
opening ¯uorination of epoxides to give ¯uorohydrins in
good to excellent yields. However, relatively higher reaction
temperatures of 788C to 1408C were needed for the reaction
[6], and therefore, the search for milder ¯uorination condi-
tions still appears to be a worthwhile goal.
2. Experimental
Ring-opening ¯uorination of epoxides was carried out as
follows: To a mixture of (NH4)2SiF6 (2.5 mmol), CsF
(0.5 mmol) and epoxide (0.5 mmol) in 1,2-dichloroethane
(5 ml) was added 47% hydro¯uoric acid (1.5 mmol) at 08C,
and the mixture was stirred for 5±12 h at 08C until all the
starting material disappeared on TLC. A saturated aqueous
NaHCO3 was added and the whole mixture was extracted
with ether. After usual work-up the crude oil was puri®ed on
preparative silica gel TLC to give ¯uorohydrin.
Several years ago we reported that the addition of a certain
metal ¯uoride to the reaction system using (HF)nÁPy com-
plex promoted the desired ¯uorination reactions, giving
¯uorinated products in good yields [7±12]. Furthermore,
we have also found that silicon tetra¯uoride serves as a
good ¯uorine source when an appropriate additive is present
[13±18].
3. Results and discussion
The results of ring-opening ¯uorination of epoxide 1 are
shown in Table 1.
During investigations using SiF4, hypervalent ¯uorosi-
lanes have been found to show suf®cient nucleophilicities
As shown in Table 1 the present ring-opening ¯uorination
was sensitive to the presence of additives. In the absence of
the additive, the reaction gave the desired ¯uorohydrine 2 in
*Corresponding author. Tel.: +81-59-231-9414; fax: +81-59-231-9413
E-mail address: mshimizu@chem.mie-u.ac.jp (M. Shimizu)
0022-1139/99/$ ± see front matter # 1999 Elsevier Science S.A. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 9 9 ) 0 0 1 8 0 - 3

96
M. Shimizu, Y. Nakahara / Journal of Fluorine Chemistry 99 (1999) 95±97
Table 1
Ring-opening fluorination of epoxide 1a
Table 3
Ring-opening fluorination of epoxide 3a
Entry
47% HF (eq) Additive (eq)
Yield of 2 (%)b
Entry
HF
Fluorosilane (eq) Solvent
Yield of 4 (%)b
1
2
3.0
3.0
3.0
5.0
5.0
5.0
5.0
5.0
5.0
3.0
None
(NH4)2SiF6 (5.0)
34
46
67
61
57
1
2
47%
47%
None Et2O
(NH4)2SiF6 (5.0) PhCH3
0
62
18
52
38
0
3
(NH4)2SiF6 (5.0), CsF (1.0)
(NH4)2SiF6 (5.0), CsF (2.0)
(NH4)2SiF6 (5.0), NaF (3.0)
3
47%
Na2SiF6 (5.0)
PhSiF3 (5.0)
PhMeSiF2 (5.0)
None
Et2O
PhCH3
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
4
4
47%
5
5
47%
Anhydrous
None
6
(NH4)2SiF6 (5.0), SnF2 (3.0) 47
6
7
Cs2SiF6 (2.0)
59
53
46
21
7
SiF4 (excess)
PhSiF3 (5.0)
SiF4 (excess)
PhSiF3 (5.0)
0
8
CaSiF6 (5.0)
BaSiF6 (5.0)
8
None
Anhydrous
Anhydrous
0
9
9
70
75
10
(BnMe3N)2SiF6 (2.4)
10
a The reaction was carried out according to the typical experimental
procedure.
b Isolated yield.
a The reaction was carried out according to the typical experimental
procedure.
b Isolated yield.
proceeded via an transition state A due to the steric con-
gestion between Ph and Me groups in intermediate B,
leading to predominant formation of syn-4 in every case
[19±21].
The ring-opening ¯uorination of 2,2-disubstituted epox-
ides was next examined, and the results are summarized in
Table 3.
As shown in Table 3, 47% hydro¯uoric acid in the
absence of additives did not effect the formation of ¯ur-
ohydrin 4 (entry 1), whereas the presence of (NH4)2SiF6
promoted its formation to give 4 in 62% yield. Although the
use of anhydrous HF, SiF4, or PhSiF3 itself also did not give
the desired ¯uorohydrin, a combined use of anhydrous HF
with SiF4 or PhSiF3 was considerably effective for the
formation of ¯uorohydrin 4 which might be produced
through a different reaction pathway from the other exam-
ples (entries 6±10).
The ring-opening ¯uorination of 2,2,3-trisubstituted
epoxide and epoxysilane was also examined. In the cases
of the epoxides 5 and 7, the presence of iPr2NEt was crucial
to prevent the rearrangement of the epoxides [22±24], and
the presence of added (NH4)2SiF6 and iPr2NEt was effective
for the formation of the ¯urohydrins 6 and 8 in moderate
yields (Scheme 1).
Table 2
Ring-opening fluorination of epoxide 3a
Entry
HF
Additive (eq)
Yield of
4 (%)b
syn : antic
1
2
3
47%
47%
47%
(NH4)2SiF6 (5.0)
iPr2NEt (1.0)
(NH4)2SiF6 (5.0),
CsF (1.2)
45
41
45
7.0 : 1.0
5.5 : 1.0
20.0 : 1.0
4
Anhydrous
PhSiF3 (5.0)
25
11.0 : 1.0
a The reaction was carried out according to the typical experimental
procedure.
b Isolated yield.
c Determined by 1H NMR.
low yield, whereas the presence of a certain hexa¯uorosi-
licate promoted the ring-opening ¯uorination. The best
result was obtained in the presence of (NH4)2SiF6
(5.0 eq) and CsF (1.0 eq), and the ¯uorohydrin 2 was
obtained in 67% yield (entry 4).
As shown in Table 2, an interesting selectivity was
observed in the ring-opening ¯uorination of epoxide 3.
The formation of syn-isomer syn-4 always predominated.
This may be due to the hydrogen bonding and/or silyl ether
formation as shown in Fig. 1. The ¯uorination probably
Fig. 1. Possible intermediates for the formation of 4.
Scheme 1. Ring-opening fluorination of trisubstituted epoxides.

M. Shimizu, Y. Nakahara / Journal of Fluorine Chemistry 99 (1999) 95±97
97
[8] S. Kanemoto, M. Shimizu, H. Yoshioka, J. Chem. Soc., Chem.
Commun. (1989) 690.
4. Conclusions
[9] M. Shimizu, G. Chang, H. Yoshioka, J. Fluorine Chem. 41 (1988)
245.
In conclusion, the present ring-opening ¯uorination of
epoxides using hydro¯uoric acid offers a convenient pro-
cedure for the synthesis of ¯uorohydrins. Since hydro¯uoric
acid and epoxides are readily accessible and the experi-
mental procedure is not tedious, this approach may broaden
the use of hydro¯uoric acid for the introduction of ¯uorine
atoms into organic molecules.
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