Meerwein arylation with 3-fluorobutenone

Article abstract of DOI:10.1016/j.jfluchem.2009.12.009

3-Fluorobutenone (7) reacts with aryl triazenes in the presence of zinc iodide to give 4-aryl-3-fluoro-3-iodo-2-butanones (9a-9f) in moderate yields. The products arise from a free radical process that terminated by iodination of an alkyl radical. The process yields unusual geminal iodo-fluoro compounds.

Full text of DOI:10.1016/j.jfluchem.2009.12.009

Journal of Fluorine Chemistry 131 (2010) 396–397
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Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Meerwein arylation with 3-fluorobutenone
*
Timothy B. Patrick , Dennis Awasabisah
Department of Chemistry, Southern Illinois University, Edwardsville, IL 62026, USA
A R T I C L E I N F O
A B S T R A C T
Article history:
3-Fluorobutenone (7) reacts with aryl triazenes in the presence of zinc iodide to give 4-aryl-3-fluoro-3-
iodo-2-butanones (9a–9f) in moderate yields. The products arise from a free radical process that
terminated by iodination of an alkyl radical. The process yields unusual geminal iodo-fluoro compounds.
ß 2009 Elsevier B.V. All rights reserved.
Received 30 November 2009
Received in revised form 9 December 2009
Accepted 10 December 2009
Available online 21 December 2009
Keywords:
Meerwein arylation
Aryltriazenes
Geminal iodo-fluoro function
Fluorovinyl ketone
1. Introduction
the first activated fluoroalkene. As seen in Scheme 3 several aryl
radicals produced from aryl triazenes (8a–8f) [8] and ZnI2 were
Meerwein arylation is a well known process for the addition
of an aryl radical to an activated unsaturated function to give
both unsaturated and saturated aryl products [1,2] (Scheme 1).
An aryl diazonium salt (1) reacts with a metal catalyst to
generate an aryl radical A. The radical reacts with an activated
unsaturated system, methyl vinyl ketone (2) in this example, to
give an alkyl radical B. The radical can be terminated by addition
of halogen to give the saturated product 3 that can be isolated or
can be dehydrohalogenated to give the arylated unsaturated
system 4. Yields are generally moderate to good depending on
the ratios of diazonium salt, vinyl compound and catalyst.
Sometimes appreciable amounts of aryl halide are formed from
a Sandmeyer process.
allowed to react with 7 to give the unusual geminal fluoro-iodo
products (9a–9f) in moderate yields (Table 1).
These reactions do not show any unsaturated products, but
products from iododediazotization (ArI) are always observed in
12–15% yields. The rates of aryl addition to 7 (approx. 108) and of
aryl iodination (approx. 107–8) should be very similar according to
Heinrich [1]. The best way to control the outcome is by varying the
amounts of reactants. We found after many attempts that the best
ratio of 7/8/ZnI2 is 10/1/2. We could not find conditions to stop
formation of the iodoaromatic compound.
The geminal fluoro-iodo function is rarely observed. We have
only found records of iodo-fluoro methanes and ethanes and some
minor products from iodofluorination [9]. In comparison of the F
NMR chemical shifts of products 9a–9f with a similar non-
iodinated compound [6], we find that the fluoro-iodo compounds
are approximately 67 ppm downfield from hydro-fluoro com-
pound. The large deshielding effect of iodine atoms on proton NMR
spectroscopy is reported in the literature and apparently holds also
for fluorine NMR [10].
2. Results and discussion
In 2001 we reported the use of aryl triazines as radical sources
for the Meerwein reaction with acrylonitrile to give addition
products terminated by iodination as shown in Scheme 2 [3].
Our recent studies on the chemistry of 3-fluorobutenone (7) [4–
6] led us to investigate the Meerwein arylation of this fluorinated
unsaturated system (Scheme 3). Although several non-activated
vinyl fluorides have been studied in the Meerwein reaction [7], 7 is
When equivalent amounts of 7 and methyl vinyl ketone, both in
excess, were allowed to react with phenyl triazine, equal amounts
of phenyl radical products from both substrates were observed.
Thus 7 and methyl vinyl ketone show the very similar reactivity in
the reaction, with little effect from the fluorine atom of 7.
3. Experimental procedure
* Corresponding author at: Department of Chemistry, Southern Illinois Universi-
ty, Box 1652, Edwardsville, IL 62026, USA. Tel.: +1 618 650 3582;
fax: +1 618 650 4665.
The preparation of 7 [4] and of aryl triazines (8a–8f) [9] have
E-mail address: tpatric@siue.edu (T.B. Patrick).
been reported.
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.12.009

T.B. Patrick, D. Awasabisah / Journal of Fluorine Chemistry 131 (2010) 396–397
397
J = 19.1 Hz, CH2),
(m, aromatic),
d
d
88.0, 91.6 (d, J = 271.9 Hz, CFI),
201.1 (d, J = 28.7 Hz, CO). Anal. Calcd for
d
128.0–134.0
C10H10FIO: m/e 291.976. Found, 291.977.
3-Fluoro-3-iodo-4-p-tolylbutan-2-one (9b): 1H NMR (CDCl3,
TMS)
3.77 (dq, JH–H = 14.7 Hz, JH–F = 10.0 Hz, JH–F = 2.0 Hz, 2H, CH2),
7.12 (s, 4 H aromatic); 13C NMR (CDCl3, TMS)
21.4 (s, Ph–CH3),
23.6 (d, J = 4.0 Hz, CH3), 48.4 (d, J = 19.1 Hz, CH2), 88.8, 92.4 (d,
J = 271.9 Hz, CFI), 129.3–137.7 (m, aromatic), 201.5 (d,
d 2.30 (d, J = 4.6 Hz, 3H, CH3), d 2.32 (s, 3H, Ph–CH3), d 3.67–
d
d
d
d
d
Scheme 1.
d
d
J = 28.7 Hz, CO). Anal. Calcd for C11H12FIO: m/e 305.991. Found,
305.989.
3-Fluoro-3-iodo-4-(4-methoxyphenyl)butan-2-one (9c): 1H
NMR (CDCl3, TMS)
(dq, JH–H = 15 Hz, JH–F = 8.5 Hz, JH–F = 1.5 Hz, 2H, CH2),
OCH3),
23.6 (d, J = 3.0 Hz, CH3),
88.5, 91.5 (d, J = 271.9 Hz, CFI),
d
2.29 (d, J = 4.9 Hz, 3H, CH3),
d
d
3.65–3.78
3.79 (s, 3H,
d
6.82–7.23 (dm, 4 H aromatic); 13C NMR (CDCl3, TMS)
d
Scheme 2.
d
48.0 (d, J = 19.1 Hz, CH2),
d 55.5 (s, OCH3),
d
d
114.0–159.3 (m, aromatic), d
201.7 (d, J = 28.7 Hz, CO). Anal. Calcd for C11H12FIO2: m/e 321.986.
Found, 321.984.
3-Fluoro-3-iodo-4-m-tolylbutan-2-one (9d): 1H NMR (CDCl3,
TMS)
3.77 (dq, JH–H = 14.6 Hz, JH–F = 9.3 Hz, JH–F = 1.5 Hz, 2H, CH2),
7.04–7.24 (m, 4 H aromatic); 13C NMR (CDCl3, TMS)
23.61
(d, J = 3.0 Hz, CH3), 48.70 (d, J = 19.1 Hz, CH2), 88.70, 92.30
(d, J = 272.5 Hz, CFI), 128.06–157.15 (m, aromatic), 201.10
d 2.31 (d, J = 4.9 Hz, 3H, CH3), d 2.34 (s, 3H, Ph–CH3), d 3.67-
d
d
Scheme 3.
d
d
d
d
Table 1
Fluoro-iodo products from Meerwein Arylation of 7.
(d, J = 28.2 Hz, CO). Anal. Calcd for C11H12FIO: m/e 305.991. Found,
305.990.
4-(4-Chlorophenyl)-3-fluoro-3-iodobutan-2-one (9e) 1H NMR
Fluoro-iodo products (9)
% yield
dF 19 (CFCl3)
(CDCl3, TMS)
H = 14.7 Hz, JH–F = 10.3 Hz, JH–F = 3.2 Hz, 2H, CH2),
4 H aromatic); 13C NMR (CDCl3, TMS)
23.42 (d, J = 2.0 Hz, CH3),
48.80 (d, J = 19.1 Hz, CH2), 87.98, 91.59 (d, J = 271.9 Hz, CFI),
128.04–134.0 (m, aromatic), 200.87 (d, J = 28.2 Hz, CO). Anal.
d
2.33 (d, J = 4.9 Hz, 3H, CH3),
d
3.66–3.76 (dq, JH–
H
9a
45
51
78
46
35
27
À122.1
À122.0
À122.2
À121.7
À123.3
À123.2
À115.3 p-F
d
7.13–7.27 (dm,
p-CH3
p-OCH3
m-CH3
p-Cl
9b
9c
9d
9e
9f
d
d
d
d
d
p-F
Calcd for C10H9ClFIO: m/e 325.937. Found, 325.927.
3-Fluoro-4-(4-fluorophenyl)-3-iodobutan-2-one (9f): 1H NMR
(CDCl3, TMS)
H = 15 Hz, JH–F = 10.3 Hz, JH–F = 3.2 Hz, 2H, CH2),
H aromatic); 13C NMR (CDCl3, TMS)
26.74 (d, J = 4.5 Hz, CH3),
37.47 (d, J = 20.1 Hz, CH2), 94.66, 97.16 (d, J = 188.3 Hz, CFI),
115.48–163.92 (m, aromatic), 208.0 (d, J = 28.2 Hz, CO). Anal.
d
2.32 (d, J = 4.9 Hz, 3H, CH3),
d
3.66–3.76 (dq, JH–
d 6.97–7.26 (dm, 4
3.1. General procedure for the ZnI2 catalyzed Meerwein arylation of 7
1-Phenyl-2-(piperidin-1-yl)diazene (8a) (1.14 mmol,
d
d
d
d
215.7 mg), ZnI2 (2.28 mmol, 727.7 mg), and 3-fluorobutenone
(7) (11.4 mmol, 1 g) in 10 mL of acetonitrile were placed in a clean
dry 25 mL round bottom flask. The flask was degassed and sealed
under argon. The flask was stirred vigorously overnight. Acetoni-
trile and excess 3-fluorobutenone (7) were removed by vacuum
evaporation followed by filtration on a short plug of silica gel to
remove excess ZnI2. The crude product was purified by flash
column chromatography using hexane/ethyl acetate solvent
gradient. An oily compound (9a) was obtained in 45% yield.
Compounds 9a–9f were all obtained as amber oils.
d
Calcd for C10H9F2IO: m/e 309.967. Found, 309.968.
Acknowledgement
This research was funded by the National Science Foundation
RUI program.
References
[1] M.R. Heinrich, Chem. Eur. J. 15 (2009) 820.
[2] C.S. Rondestvedt Jr., Org. React. 24 (1976) 225.
3.2. Analytical data for 9a–9f
[3] T.B. Patrick, T. Juehne, E. Reeb, D. Hennessy, Tetrahedron Lett. 42 (2001) 3553.
[4] T.B. Patrick, T.Y. Agboka, K. Gorrell, J. Fluorine Chem. 129 (2008) 983.
[5] T.B. Patrick, H. Li, J. Fluorine Chem. 130 (2009) 544.
[6] T.B. Patrick, U.P. Dahal, J. Fluorine Chem. 130 (2009) 470.
[7] C.S. Rondestvedt Jr., J. Org. Chem. 42 (1977) 2618.
[8] D.F. Shellhamer, V.L. Heasley, Adv. Org. Synth. 2 (2006) 43.
[9] T.B. Patrick, R.P. Willaredt, D.J. Degonia, J. Org. Chem. 50 (1985) 2232.
[10] R.J. Abraham, M.A. Warne, L. Griffiths, J. Chem. Soc., Perkin Trans. 2 (1997) 215.
F NMR spectra are reported in Table 1 with a reference of CFCl3.
3-Fluoro-3-iodo-4-phenylbutan-2-one (9a): 1H NMR (CDCl3,
TMS)
JH–F = 10.0 Hz, JH–F = 2.1 Hz, 2H, CH2),
ic); 13C NMR (CDCl3, TMS)
23.4 (d, J = 2.0 Hz, CH3),
d
2.30 (d, J = 4.6 Hz, 3H, CH3),
d
3.70–3.80 (dq, JH–H = 14.7 Hz,
7.26–7.32 (m, 5H aromat-
47.80 (d,
d
d
d