Iodofluorination of alkenes and alkyne using electrochemically generated iodonium cation

Article abstract of DOI:10.1055/s-2001-18775

Iodofluorination reaction of alkenes and alkynes using the iodonium ion electrochemically generated in situ from the iodide anion was carried out. The reaction proceeds at room temperature to provide iodofluorination products regioselectively.

Full text of DOI:10.1055/s-2001-18775

1938
LETTER
Iodofluorination of Alkenes and Alkyne using Electrochemically Generated
Iodonium Cation
I
odofluorinatio
h
n of Alkene
i
and
A
n
lkynes go Kobayashi, Masanori Sawaguchi, Shinichi Ayuba, Tsuyoshi Fukuhara, Shoji Hara*
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
Fax +81(11)7066556; E-mail: Hara@org-mc.eng.hokudai.ac.jp
Received 13 September 2001
Table 1 Effect of Iodide Anion Source on the Iodofluorination of 1-
Abstract: Iodofluorination reaction of alkenes and alkynes using
the iodonium ion electrochemically generated in situ from the io-
dide anion was carried out. The reaction proceeds at room tempera-
ture to provide iodofluorination products regioselectively.
Dodecenea
F
I –-Et3N-5HF
CH2Cl2
-2e
I
Key words: alkenes, fluorine, halogenation, iodine, regiose-
lectivity
C10H21
C10H21
I– Source
V (vs. Ag/Ag+)
Electricity
Yield (%)b
(Fmol–1)
The iodofluorination reaction has been used to produce
fluoroiodoalkanes from alkenes under mild conditions
(Equation).1 One disadvantage of the reaction is the inac-
Et4NI
Me4NI
Ph4PI
1.2
1.4
1.5
1.4
1.2
1.2
2.0
93
2.0
68
cessibility of iodonium cation (I+) sources. As the iodoni-
1.5
56 (44)
69 (25)
90
2,3
um cation source, I2,2 NIS,
IF,4 I(pyridine)2BF4,5 and
6
c
I(collidine)2BF4 have been used. However, application of
I2 caused the formation of diiodo compounds,2 and NIS is
expensive. Other iodonium cation sources are not com-
mercially available; furthermore, dangerous F2 gas,4 ex-
pensive Ag salts,4 or harmful Hg salts5 are necessary for
their preparation. Therefore, an economical and easily ac-
cessible source of the iodonium cation is necessary for de-
velopment of the iodofluorination reaction. We wish to
report here an iodofluorination reaction using the iodoni-
um cation electrochemically generated from cheap iodide
anion (I–).
I2
0.8
NaI
LiI
2.0
1.7
66 (21)d
a If otherwise not mentioned, the reaction was carried out at room
temperature using 1.1 equivalents of iodide anion source to dodecene
in a 1:1 mixture of Et3N-5HF and CH2Cl2.
b GC yield. In parentheses, the yield of recovered dodecene.
c 0.55 equivalents of I2 to dodecene was used.
d 1,2-Diiododecane was also formed in 5% yield.
F
lectivity could be improved to 96% by carrying out the re-
action at –10 °C.
R
I +
F
R
R
R
Various kinds of alkenes were subjected to the iodofluori-
nation reaction using the electrochemically generated io-
donium cation,8,9 and high stereo- and regioselectivity
could be realized compared with the previous methods2–6
(Table 2). For 2,2-disubstituted alkenes, less acidic Et3N-
4HF was used instead of Et3N-5HF because hydrofluori-
nation reaction of a double bond took place during the
electrolysis (entries 3 and 5).10 Functional groups such as
an ester or a hydroxy group can tolerate the reaction con-
ditions though 2 equivalents of Et4NI to the substrate was
necessary to complete the reaction (entries 6 and 7). In the
iodofluorination reactions of 1-alkynes, it is difficult to
obtain 2-fluoro-1-iodo-1-alkenes.1b However, in this reac-
tion using the electrochemically generated iodonium cat-
ion, (E)-2-fluoro-1-iodo-1-alkene could be obtained
stereo- and regioselectively (entry 9).11
I
Equation
Electrolysis for iodofluorination of dodecene was carried
out using a variety of iodide anion sources, and Et3N-5HF
as the electrolyte and fluorine source in CH2Cl2.7 The
electrolysis was continued at room temperature under
constant potential until dodecene was completely con-
sumed. When Ph4PI, I2, LiI were used, passivation on the
anode took place before the complete consumption of
dodecene. Consequently, Et4NI and NaI were found to be
suitable for the iodonium cation source, and 1-iodo-2-flu-
orododecane was obtained in more than 90% yield with
5% of 1-fluoro-2-iodododecane (Table 1). The regiose-
Synlett 2001, No. 12, 30 11 2001. Article Identifier:
1437-2096,E;2001,0,12,1938,1940,ftx,en;Y18201ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
Iodofluorination of Alkenes and Alkyne
1939
Table 2 Iodofluorination of Alkenes and Alkyne Using Eelectrochemically Generated Iodonium Cationa
Entry
Substrate
C10H21
V (vs. Ag/Ag+) Electricity
(Fmol–1)
Product
C10H21
Regioselectivi- Yield (%)b
ty (%)
F
1
2
1.2
1.0
2.0
2.0
96
80 (100)c, (100)c,d
(90), (100)d
I
F
I
F
3
4
1.4
1.2
2.0
2.1
> 98
(99)e, (100)d,e
I
f
F
84
I
F
5
6
7
1.2
1.5
1.4
2.1
2.9
3.7
> 98
77e
I
C9H19
C9H19
F
95
97
90g
75g
MeOOC-(CH2)8
HO-(CH2)9
I
MeOOC-(CH2)8
F
I
HO-(CH2)9
F
68
65
Ph
8
9
1.1
1.4
2.0
4.0
98
I
Ph
F
> 99
C10H21
C
CH
C10H21
I
a If otherwise not mentioned, the reaction was carried out at room temperature using 1.1 equivalents of Et4NI to substrate in a 1:1 mixture of
Et3N-5HF and CH2Cl2.
b Isolated yield based on substrate used, in parentheses, GC yield.
c The reaction was carried out at -10 °C.
d NaI was used instead of Et4NI.
e Et3N-4HF was used instead of Et3N-5HF.
f A 1:1 mixture of stereoisomers was used.
g 2 equivalents of Et4NI to substrate was used.
J. Org. Chem. 1989, 54, 4294. (g) Ichihara, J.; Funabiki, K.;
References
Hanafusa, T. Tetrahedron Lett. 1990, 31, 3167.
(1) (a) Hiyama, T. In Organofluorine Compounds; Springer:
(h) Shimizu, M.; Okamura, M.; Fujisawa, T. Bull. Chem.
Heidelberg, 2000, 56. (b) Feiring, A. E. In Chemistry of
Soc. Jpn. 1991, 64, 2596. (i) Tamura, M.; Shibakami, M.;
Organic Fluorine Compounds II; Hudlicky, M.; Pavlath, A.
Sekiya, A. Synthesis 1995, 515. (j) Kuroboshi, M.; Hiyama,
E., Eds.; ACS Monograph 187: Washington, 1995, 61.
(2) Olah, G. A.; Welch, J. T.; Vankar, Y. D.; Nojima, M.;
Kerekes, I.; Olah, J. A. J. Org. Chem. 1979, 44, 3872.
(3) (a) Bowers, A.; Ibáñez, L. C.; Denot, E.; Becerra, R. J. Am.
T. Bull. Chem. Soc. Jpn. 1995, 68, 1799.
(4) (a) Schmidt, H.; Meinert, H. Angew. Chem. 1960, 72, 493.
(b) Hall, L. D.; Manville, J. F. Can. J. Chem. 1969, 47, 361.
(c) Hall, L. D.; Jones, D. L. Can. J. Chem. 1973, 51, 2914.
Chem. Soc. 1960, 82, 4001. (b) Wood, K. R.; Kent, P. W.;
(d) Rozen, S.; Brand, M. J. Org. Chem. 1985, 50, 3342.
Fisher, D. J. Chem. Soc. C 1966, 912. (c) Olah, G. A.;
Nojima, M.; Kerekes, I. Synthesis 1973, 780. (d) Alvernhe,
(e) Rozen, S.; Brand, M. J. Org. Chem. 1986, 51, 222.
(f) Ando, T.; Cork, D. G.; Fujita, N.; Kimura, T.; Tatsuno, T.
G.; Laurent, A.; Haufe, G. Synthesis 1987, 562.
Chem. Lett. 1988, 1877.
(e) Gregorcic, A.; Zupan, M. Bull. Chem. Soc. Jpn. 1987, 60,
3083. (f) Camps, F.; Chamorro, E.; Gasol, V.; Guerrero, A.
Synlett 2001, No. 12, 1938–1940 ISSN 0936-5214 © Thieme Stuttgart · New York

1940
S. Kobayashi et al.
LETTER
(5) (a) Barluenga, J.; González, J. M.; Campos, P. J.; Asensio,
G. Angew. Chem., Int. Ed. Engl. 1985, 24, 319.
CDCl3): = 4.56 (dm, J = 47.6 Hz, 1 H), 4.15–4.08 (m, 1 H),
2.41–2.36 (m, 1 H), 2.26–2.16 (m, 1 H), 2.00–1.82 (m, 2 H),
(b) Barluenga, J.; Campos, P. J.; González, J. M.; Suárez, J.
L. J. Org. Chem. 1991, 56, 2234. (c) Eddarir, S.; Francesch,
C.; Mestdagh, H.; Rolando, C. Bull. Soc. Chim. Fr. 1997,
134, 741.
1.64–1.27 (m, 4 H); 19F NMR (376 MHz, CDCl3/C6F6):
–159.9 to –160.5 (m, 1 F).
=
trans-1-Fluoro-2-iodo-1-methylcyclohexane:3j 1H NMR
(400 MHz, CDCl3): = 4.40–4.35 (m, 1 H), 2.29–2.10 (m, 2
H), 1.98–1.90 (m, 1 H), 1.79–1.71 (m, 2 H), 1.64–1.42 (m, 3
H), 1.56 (d, J = 22.4 Hz, 3 H); 19F NMR (376 MHz, CDCl3/
C6F6): = –131.3 to –133.9 (m, 1 F).
(6) Evans, R. D.; Schauble, J. H. Synthesis 1987, 551.
(7) As for the electrochemical fluorination reaction using Et3N-
nHF as the electrolyte and fluorine source, see: (a) Hara, S.;
Chen, S.-Q.; Hoshio, T.; Fukuhara, T.; Yoneda, N.
Tetrahedron Lett. 1996, 37, 8511. (b) Chen, S.-Q.;
Hatakeyama, T.; Fukuhara, T.; Hara, S.; Yoneda, N.
Electrochim. Acta 1997, 42, 1951. (c) Sawaguchi, M.;
Ayuba, S.; Nakamura, Y.; Fukuhara, T.; Hara, S.; Yoneda,
N. Synlett 2000, 999.
(8) A typical procedure for the iodofluorination reaction using
electrochemically generated iodonium cation. Et3N-5HF
(12 mL) and CH2Cl2 (12 mL) were introduced into a divided
cell, made of Teflon™ PFA, equipped with a Nafion™
117 film as the diaphragm using two smooth Pt Sheets (20
mm 20 mm) for the anode and cathode under a nitrogen
atmosphere. 1-Dodecene (168 mg, 1 mmol) and Et4NI (283
mg, 1.1 mmol) were then added into the anodic cell. The
electrolysis was carried out at –10 °C with a constant
potential (1.20 V vs Ag/Ag+) until 2 F/mol of electricity had
passed. The content of the anode cell was then poured into
water and extracted three times with CH2Cl2. The combined
organic layers were successfully washed with aq Na2S2O3,
aq NaHCO3, and brine, and dried over MgSO4. The puri-
fication by column chromatography (silica gel/hexane) gave
2-fluoro-1-iodo-dodecane in 77% yield together with 3%
yield of 1-fluoro-2-iodododecane.
1-Fluoro-2-iodocyclododecane:3d 1H NMR (400 MHz,
CDCl3): = 4.50–4.30 (m, 2 H), 2.07–1.34 (m, 20 H); 19
F
NMR (376 MHz, CDCl3/C6F6): = –169.2 to –169.6 (m, 1
F).
2-Fluoro-1-iodo-2-methylundecane:3j 1H NMR (400 MHz,
CDCl3): = 3.34 (d, J = 16.6 Hz, 2 H), 1.84–1.74 (m, 2 H),
1.49 (d, J = 21.2 Hz, 3 H), 1.27 (br s, 14 H), 0.88 (t, J = 6.7
Hz, 3 H); 19F NMR (376 MHz, CDCl3/C6F6): = –140.42 to
–140.78 (m, 1 F).
Methyl 10-fluoro-11-iodoundecanoate:3i 1H NMR (400
MHz, CDCl3): = 4.45 (dm, J = 47.8 Hz, 1 H), 3.67 (s, 3 H),
3.53–3.37 (m, 2 H), 2.31 (t, J = 7.4 Hz, 2 H), 1.76–1.60 (m,
4 H), 1.31 (br s, 10 H); 19F NMR (376 MHz, CDCl3/C6F6):
= –171.2 to –171.6 (m, 1 F).
10-Fluoro-11-iodo-1-undecanol: IR(neat): 3321, 1467 cm–1;
1H NMR (400 MHz, CDCl3): = 4.45 (dm, J = 47.3 Hz, 1
H), 3.65 (t, J = 6.7 Hz, 2 H), 3.35–3.27 (m, 2 H), 1.79–1.68
(m, 2 H), 1.60–1.53 (m, 2 H), 1.31 (br s, 12 H); 19F NMR
(376 MHz, CDCl3/C6F6): = –171.2 to –171.6 (m, 1 F).
1-Fluoro-2-iodo-1-phenylethane:3i 1H NMR (400 MHz,
CDCl3): = 7.40–7.25 (m, 5 H), 5.55 (dm, J = 45.9 Hz, 1 H),
3.54–3.40 (m, 2 H); 19F NMR (376 MHz, CDCl3/C6F6):
–167.0 to –167.3 (m, 1 F).
=
(9) 2-Fluoro-1-iodododecane:3j IR(neat): 1467 cm–1; 1H NMR
(400 MHz, CDCl3): = 4.46 (dm, J = 47.8 Hz, 1 H), 3.37–
3.24 (m, 2 H), 1.78–1.63 (m, 2 H), 1.26 (br s, 16 H), 0.88 (t,
J = 6.4 Hz, 3 H); 19F NMR (376 MHz, CDCl3/C6F6): = –
171.2 to –171.6 (m, 1 F); HRMS (EI): m/z calcd for
C12H24FI: 314.0907; found 314.0904.
(E)-2-Fluoro-1-iodo-1-dodecene: IR(neat): 1645 cm–1; 1H
NMR (400 MHz, CDCl3): = 5.63 (d, J = 17.7 Hz, 1 H),
2.46 (dt, J = 23.0, 7.6 Hz, 2 H), 1.56–1.44 (m, 2 H), 1.32–
1.20 (m, 14 H), 0.85 (t, J = 6.5 Hz, 3 H); 19F NMR (376
MHz, CDCl3/C6F6): = –82.25 (dt, J = 17.7, 23.0 Hz, 1 F);
HRMS (EI): m/z calcd for C12H22FI: 312.0750; found
312.0742.
1-Fluoro-2-iodododecane: 1H NMR (400 MHz, CDCl3):
=
4.69–4.23 (m, 2 H), 4.23–4.13 (m, 1 H), 1.92–1.72 (m, 2 H),
1.27 (br s, 16 H), 0.88 (t, J = 6.7 Hz, 3 H); 19F NMR (376
MHz, CDCl3/C6F6): = –198.4 (dt, J = 13.4, 47.6 Hz, 1 F).
trans-1-Fluoro-2-iodocyclohexane:3j 1H NMR (400 MHz,
(10) Hara, S.; Kameoka, M.; Yoneda, N. Synlett 1996, 529.
(11) Recently, Mestdagh et al. succeeded to obtain 2-fluoro-1-
iodo-1-alkenes in the iodofluorination of 1-alkynes by using
I(pyridine)2BF4 as the iodonium cation source.5c
Synlett 2001, No. 12, 1938–1940 ISSN 0936-5214 © Thieme Stuttgart · New York