Preparation of α-bromo-β,β-difluorostyrenes

Full text of DOI:10.1021/jo971554w

1714
J . Org. Chem. 1998, 63, 1714-1715
Ta ble 1. Rea ction of Ar yl Iod id es w ith CF 2dCBr Zn X
P r ep a r a tion of
r-Br om o-â,â-d iflu or ostyr en es
Ca ta lyzed by P d (P P h 3)4 in DMF
Ba V. Nguyen and Donald J . Burton*
Department of Chemistry, University of Iowa,
Iowa City, Iowa 52242
Received August 20, 1997
In tr od u ction
R-Bromo-â,â-difluorostyrenes (II) are building blocks
in organofluorine chemistry due to the reactivity of the
gem-difluoromethylene terminus toward nucleophilic re-
agents, and the R-bromine provides a reaction site for
further functionalization. Until now, no methods for the
direct introduction of the CF2dCBr- group into organic
molecules have been reported. Some synthetic strategies
used to form R-halo-â,â-difluorostyrenes have been re-
ported. The first approach was the addition of a halogen
1
to RCHdCF2 followed by dehydrohalogenation.2 The
success of the dehydrohalogenation process depended on
the base employed. A more selective base was used to
improve the yields and to avoid undesired byproducts.
a
Isolated yields based on aryl iodides.
R-bromo-â,â-difluorostyrenes by the palladium-catalyzed
coupling reaction of CF2dCBrZnX with aryl iodides.
Resu lts a n d Discu ssion
An alternative method3 for the formation of R-halo-â,â-
difluorostyrenes was to heat benzotrichlorides in the
presence of chlorodifluoromethane at 575 °C. This
method gives (R,R,â-trichloro-â,â-difluoroethyl)benzene as
a byproduct, and the total yields were low. The temper-
ature was an important factor for the success of this
reaction. For example, the reaction gives 18%, 24%, and
3% yields of R-halo-â,â-difluorostyrene at 635, 575, and
535 °C, respectively.
CF2dCBrZnX (I) is prepared by treatment of CF2dCBrX
(X ) I, Br) with acid-washed zinc in DMF. This exother-
mic reaction is completed in 20 min and gives 19F NMR
yields of 98% (vs internal C6H5CF3). Zinc reagent I
reacted smoothly with aryl iodides in DMF in the
presence of catalytic amounts of Pd(PPh3)4 under mild
conditions (Table 1). Methyl, trifluoromethyl, nitro, and
methoxy groups substituted on the aryl iodides are
tolerated under the reaction conditions. For example, I
reacts with 1-iodotoluene at 60 °C in 5 h with 5 mol % of
Pd(PPh3)4 catalyst to form the corresponding coupled
product 2-methyl-R-bromo-â,â-difluorostyrene in 81%
isolated yield (Table 1, entry 1). Reaction of 2.7 equiv of
I with 1 equiv of 1,4-diiodobenzene gives 1,4-bis(1-bromo-
2,2-difluoroethenyl)benzene in 84% yield (Table 1, entry
5).
The R-bromo-â,â-difluorostyrenes and the starting aryl
iodides have similar Rf values on silica gel. Thus, it is
important to ensure that excess I is utilized so that the
reaction goes to completion. The R-bromo-â,â-difluoro-
styrenes are stable indefinitely in solvents such as
hexane, ether, and DMF; however, they are readily
decomposed (hydrolyzed) in air when solvent is absent.
Recent reports from our laboratory have demonstrated
the synthetic applications of CF2dCFZnX4 and (E)- and
(Z)-CF3CFdCFZnX.5 This success prompted us to ex-
amine the formation and synthetic applications of
F2CdCBrZnX. We now report the facile preparation of
(1) (a) Burton, D. J . J . Fluorine Chem. 1983, 23, 339. (b) Gillet, J .
P.; Sauvetre, R.; Normant, J . F. Synthesis 1986, 538. (c) Tellier, I.;
Sauvetre, R.; Normant J . F. J . Organomet. Chem. 1986, 303, 309.
(2) Burton, D. J .; Anderson, A. L.; Takei, R.; Koch, H, F.; Shih, T.
L. J . Fluorine Chem. 1980, 16, 229.
(3) Dvornikova, K. V.; Platonov, V. E.; Yakobson, G. G. J . Fluorine
Chem. 1985, 28, 99.
(4) (a) Heinze, P. L.; Burton, D. J . J . Org. Chem. 1988, 53, 2714. (b)
Spawn, T. D.; Burton, D. J . Bull. Soc. Chim. Fr., 1986, 6. (c) Hansen,
S. W.; Spawn, T. D.; Burton, D. J . J . Fluorine Chem. 1987, 35, 415.
(5) (a) Morken, P. A.; Burton, D. J . J . Org. Chem. 1993, 58, 1167.
(b) Morken, P. A.; Lu, H.; Nakamura, A.; Burton, D. J . Tetrahedron
Lett. 1991, 32, 4271.
S0022-3263(97)01554-5 CCC: $15.00 © 1998 American Chemical Society
Published on Web 02/14/1998

Notes
J . Org. Chem., Vol. 63, No. 5, 1998 1715
13C δ 153.4 (dd, J ) 293.9, 286.5 Hz), 138.4 (s), 134.0 (d, J )
19.7 Hz), 129.8 (s), 129.6 (m), 128.5 (s), 126.1 (t, J ) 5.8 Hz),
80.4 (dd, J ) 34.9, 25.6 Hz), 21.2 (s); FTIR (cm-1) 1709.0 (s),
1267.3 (s), 1172.8 (m); HRMS calcd for C9H779BrF2 231.9699,
found 231.9717.
P r ep a r a tion of 4-(1-Br om o-2,2-d iflu or oeth en yl)tolu en e
(3). Similarly, 3 was prepared from 1.1 g (5 mmol) of 4-iodo-
toluene, 7 mmol of CF2dCBrZnX, and 5 mol % of Pd(PPh3)4.
Purification of the reaction mixture by chromatography on silica
gel with hexane as eluent gave 0.9 g (77%) of clear liquid 3:
GLPC purity >99%; 19F δ -79.6 (d, J ) 32.4 Hz, 1F), -85.7 (d,
1
J ) 32.5 Hz, 1F); H δ 7.3 (d, J ) 7.5 Hz, 2H), 7.2 (d, J ) 7.5
Hz, 2H), 2.3 (s, 3H); 13C δ 153.3 (dd, J ) 293.9, 285.7 Hz), 139.1
(s), 134.0 (d, J ) 19.5 Hz), 129.4 (s), 128.9 (t, J ) 5.6 Hz), 80.4
(dd, J ) 34.3, 25.7 Hz), 21.1 (s); FTIR (cm-1) 1716.7 (s), 1276.9
(m), 1248.0 (m); HRMS calcd for C9H779BrF2 231.9699, found
231.9716.
Con clu sion
In conclusion, we have presented a new preparative
method for R-bromo-â,â-difluorostyrenes via coupling of
(R-bromo-â,â-difluoroethenyl)zinc reagent with aryl io-
dides catalyzed by Pd(PPh3)4 in DMF under mild condi-
tions. Since the zinc reagents can be produced in situ
from 1,1-dibromodifluoroethene or from 1-bromo-1-iodo-
difluoroethene, this route provides a convenient one-pot
reaction and produces the desired products directly from
commercially available materials.6
P r ep a r a t ion of 2-(1-Br om o-2,2-d iflu or oet h en yl)ben zo-
tr iflu or id e (4). Similarly, 4 was prepared from 1.4 g (5 mmol)
of 2-iodobenzotrifluoride, 8 mmol of F2CdCBrZnX, and 5 mol %
of Pd(PPh3)4. Purification of the reaction mixture by chroma-
tography on silica gel with hexane as eluent gave 1.2 g (83%) of
clear liquid 4: GLPC purity >99%; 19F δ -61.0 (s, 3F), -81.3
1
(m, 2F); H δ 7.7 (d, J ) 7.3 Hz, 1H), 7.6 (m, 1H), 7.5 (m, 2H);
13C δ 124.6 (t, J ) 181.0 Hz), 111.9 (m), 111.6 (s), 110.4 (s), 110.2
(s), 110.1 (s), 108.0 (q, J ) 3.3 Hz), 106.2 (q, J ) 170.9 Hz), 74.7
(dd, J ) 25.2, 18.6 Hz); FTIR (cm-1) 1739.9 (s), 1311.7 (s), 1284.7
(s), 1230.7 (m), 1172.8 (s), 1130.4 (s), 1112.9 (s); HRMS calcd
for C9H479BrF5 285.9416, found 285.9411.
Exp er im en ta l Section
Gen er a l Meth od s. All reactions were monitored by 19F NMR
analysis of the reaction mixtures on a 90 MHz spectrometer.
The 1H, 19F, and 13C NMR spectra of final products were obtained
on a 300 MHz spectrometer (CDCl3, CFCl3, or TMS internal
references). FT-IR spectra were recorded as CCl4 solutions in a
0.1 cm pathlength cell. Low-resolution mass spectra analyses
were performed at 70 eV in the electron-impact mode on a single
quadrapole instrument interfaced to a gas chromatograph fitted
with an OV-101 column. High-resolution mass spectral analyses
were performed by the University of Iowa High-Resolution Mass
Spectrometry Facility at 70 eV in the electron impact mode.
GLPC analyses were performed on a 5% OV-101 column and
thermal conductivity detector. The aryl iodides were obtained
from Aldrich and used directly.
P r ep a r a tion of CF 2dCBr Zn X (I). A 100 mL two-necked,
round-bottomed flask equipped with a septum, a Teflon-coated
magnetic stirbar, and N2 tee, which was connected to a mineral
oil bubbler, was charged with 1.0 g (15 mmol) of acid-washed
zinc, 8 mL of dry DMF, and 2.6 g (11.7 mmol) of CF2dCBr2.
The reaction mixture was stirred for 20 min, and 19F NMR
analysis showed two groups of signals: δ -68.8 (d, J ) 59.4 Hz,
0.3 F), -69.8 (d, J ) 56.3 Hz, 0.7 F), and -84.9 (d, J ) 56.9 Hz,
0.7 F), -85.8 (d, J ) 59.2 Hz, 0.3 F). The NMR yield was 98%
based on internal C6H5CF3.
P r ep a r a tion of 1,4-Bis(1-br om o-2,2-d iflu or oeth en yl)ben -
zen e (5). Similarly, 5 was prepared from 1.65 g (5 mmol) of
1,4-diiodobenzene, 13.6 mmol of CF2dCBrZnX, and 5 mol % of
Pd(PPh3)4. Purification of the reaction mixture by chromatog-
raphy on silica gel with hexane as eluent gave 1.5 g (84%) of
clear liquid 5: GLPC purity >99%; 19F δ -77.3 (d, J ) 27.8 Hz,
1
1F), -83.6 (d, J ) 27.5 Hz, 1F); H δ 7.5 (s); 13C δ 153.7 (dd, J
) 295.4, 288.0 Hz), 132.2 (d, J ) 4.5 Hz), 128.9 (t, J ) 3.6 Hz),
79.6 (dd, J ) 33.0, 26.8 Hz); FTIR (cm-1) 1724.5 (s), 1290.4 (s),
1251.9 (s), 995.3 (s), 910.4 (m); HRMS calcd for C10H479Br2F4
357.8615, found 357.8598.
P r ep a r a tion of 3-Nitr o-(1-br om o-2,2-d iflu or oeth en yl)-
ben zen e (6). Similarly, 6 was prepared from 2.5 g (10 mmol)
of 3-nitroiodobenzene, 13.2 mmol of CF2dCBrZnX, and 5 mol %
of Pd(PPh3)4. Purification of the reaction mixture by chroma-
tography on silica gel with hexane/ether (80/20) as eluent gave
2.54 g (96%) of clear liquid 6: GLPC purity >99%; 19F δ -75.6
(d, J ) 24.8 Hz, 1F), -82.0 (d, J ) 24.8 Hz, 1F); 1H δ 8.4 (t, J )
1.8 Hz, 1H), 8.2 (dm, J ) 8.2 Hz, 1H), 7.8 (dm, J ) 7.9 Hz, 1H),
7.6 (t, J ) 8.0 Hz, 1H); 13C δ 154.0 (dd, J ) 296.7, 288.3 Hz),
148.5 (s), 134.7 (t, J ) 3.3 Hz), 133.5 (d, J ) 4.7 Hz), 130.0 (s),
123.9 (m), 123.8 (s), 78.4 (dd, J ) 33.0, 27.2 Hz); FTIR (cm-1
)
1737.9 (s), 1535.4 (s), 1352.2 (s), 1305.9 (m), 1280.8 (m); HRMS
P r ep a r a tion of 2-(1-Br om o-2,2-d iflu or oeth en yl)tolu en e
(1). A 50 mL, two-necked, round-bottomed flask equipped with
a septum, a Teflon-coated magnetic stirbar, and N2 inlet, which
was connected to a mineral oil bubbler, was charged with 0.87
g (4 mmol) of 2-iodotoluene, 5 mmol of CF2dCBrZnX, and 5 mol
% of Pd(PPh3)4. The reaction mixture was stirred at 60 °C under
N2 atmosphere for 10 h. The reaction mixture was introduced
onto a silica gel column and eluted with hexane to give 0.76 g
(81%) of clear liquid 1: GLPC purity >99%; 19F δ -83.2 (d, J )
calcd for C8H479BrF2NO2 263.9383, found 263.9387.
P r ep a r a tion of 4-(1-Br om o-2,2-d iflu or oeth en yl)a n isole
(7). Similarly, 7 was prepared from 0.7 g (3 mmol) of 4-iodo-
anisole, 4.0 mmol of CF2dCBrZnX, and 5 mol % of Pd(PPh3)4.
Purification of the reaction mixture by chromatography on silica
gel with hexane/ether (80/20) as eluent gave 0.75 g (93%) of clear
liquid 7: GLPC purity >99%; 19F δ -80.4 (d, J ) 34.5 Hz, 1F),
1
-86.6 (d, J ) 34.5 Hz, 1F); H δ 7.4 (dm, J ) 8.1 Hz, 2H), 6.9
(dm, J ) 8.9 Hz, 2H), 3.8 (s, 3H); 13C δ 160.2 (s), 153.1 (dd, J )
292.7, 285.6 Hz), 130.3 (t, J ) 3.0 Hz), 123.9 (d, J ) 3.4 Hz),
1
32.8 Hz, 1F), -84.6 (d, J ) 32.9 Hz, 1F); H δ 7.2-7.1 (m, 4H),
2.3 (s, 3H); 13C δ 152.9 (t, J ) 288.7 Hz), 137.9 (s), 131.1 (s),
130.8 (d, J ) 3.7 Hz), 130.6 (s), 130.0 (s), 126.4 (s), 77.1 (dd, J )
41.5, 25.6 Hz), 19.3 (s); FTIR (cm-1) 1724.5 (s), 1267.3 (s), 1238.4
(m); HRMS calcd for C9H779BrF2 231.9699, found 231.9709.
P r ep a r a tion of 3-(1-Br om o-2,2-d iflu or oeth en yl)tolu en e
(2). Similarly, 2 was prepared from 0.87 g (4 mmol) of 3-iodo-
toluene, 5 mmol of CF2dCBrZnX, and 5 mol % of Pd(PPh3)4.
Purification of the reaction mixture by chromatography on silica
gel with hexane as eluent given 0.87 g (93%) of clear liquid 2:
GLPC purity >99%; 19F δ -79.2 (d, J ) 31.1 Hz, 1F), -85.2 (d,
J ) 31.4 Hz, 1F); 1H δ 7.3-7.2 (m, 3H), 7.1 (m, 1H), 2.3 (s, 3H);
114.1 (s), 80.0 (dd, J ) 35.2, 25.8 Hz), 55.2 (s); FTIR (cm-1
)
1722.5 (s), 1612.6 (s), 1302.0 (s), 1176.6 (s); HRMS calcd for
C9H779BrF2O 248.9638, found 248.9727.
Ack n ow led gm en t. We would like to thank the
National Science Foundation for support of this work.
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra of
all compounds (7 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
(6) CF2dCBr2 is available from PCR or can be readily prepared from
F2CdCH2 via a succession of bromination, dehydrobromination reac-
tions. F2CdCBrI was prepared by quenching [F2CdCBrZnBr] with I2.
J O971554W