Stereoselective preparation of (Z)-α,β-difluorostyrenes and stereospecific conversion to (E)-α,β-difluoro-β-iodostyrenes

Article abstract of DOI:10.1021/jo971434o

Substituted aromatic iodides coupled with (E)-HFC=CFZnI (E:Z 95.5) under mild conditions, in the presence of catalytic Pd(PPh₃)₄, in DMF to give (Z)-α,β-difluorostyrenes in good yields. The coupling reaction was tolerant of a variety of functionalities. Isomerically pure (Z)-α,β-difluorostyrenes were readily converted to the corresponding (E)-α,β-difluoro-β- iodostyrenes in good yields by two methods; in one method, treatment of the (Z)-α,β-difluorostyrenes with LTMP at low-temperature gave vinyllithium reagents which were captured in situ with Bu₃SnCl to form vinylstannanes. The intermediate vinylstannanes could be isolated or treated directly with I₂ to give (E)-α,β-difluoro-β-iodostyrenes in a one-flask procedure. In a second approach, n-BuLi was utilized to pregenerate vinyllithium reagents which were quenched with I₂ to afford (E)-α,β-difluoro-β-iodostyrenes.

Full text of DOI:10.1021/jo971434o

J . Org. Chem. 1997, 62, 9217-9222
9217
Ster eoselective P r ep a r a tion of (Z)-r,â-Diflu or ostyr en es a n d
Ster eosp ecific Con ver sion to (E)-r,â-Diflu or o-â-iod ostyr en es1
Charles R. Davis2 and Donald J . Burton*
Department of Chemistry, University of Iowa, Iowa City, Iowa 52242
Received August 4, 1997X
Substituted aromatic iodides coupled with (E)-HFCdCFZnI (E:Z 95:5) under mild conditions, in
the presence of catalytic Pd(PPh3)4, in DMF to give (Z)-R,â-difluorostyrenes in good yields. The
coupling reaction was tolerant of a variety of functionalities. Isomerically pure (Z)-R,â-difluorosty-
renes were readily converted to the corresponding (E)-R,â-difluoro-â-iodostyrenes in good yields by
two methods; in one method, treatment of the (Z)-R,â-difluorostyrenes with LTMP at low-
temperature gave vinyllithium reagents which were captured in situ with Bu3SnCl to form
vinylstannanes. The intermediate vinylstannanes could be isolated or treated directly with I2 to
give (E)-R,â-difluoro-â-iodostyrenes in a one-flask procedure. In a second approach, n-BuLi was
utilized to pregenerate vinyllithium reagents which were quenched with I2 to afford (E)-R,â-difluoro-
â-iodostyrenes.
In tr od u ction
but this method is applicable to the preparation of only
the (Z)-isomers.6 (Z)-PhCFdCFI has been prepared via
iodination of (E)-PhCFdCFLi.11 More recently, a series
of the (Z)-isomers has been prepared by iodination of (Z)-
2-aryl-1,2-difluorovinylphosphoranes.13 The paucity of
methodology for the preparation of (E)-â-iodostyrenes
analogues has impeded their utility as synthetic inter-
mediates and has been due, in part, to the lack of suitable
stereodefined precursors. Here we describe in detail the
stereoselective preparation of (Z)-R,â-difluorostyrenes
and their subsequent conversion to (E)-R,â-difluoro-â-
iodostyrenes.
Fluorinated styrenes are useful building blocks in
organofluorine chemistry and have found application as
monomers,3 as precursors for antiinflammatory4 and
antifertility5 compounds, and as precursors for 1,4-diaryl-
perfluoro-1,3-butadienes.6
Several strategies have been applied in the preparation
of R,â-difluorostyrenes. R,â-Difluorostyrene has been
prepared in low yield by dehalogenation of 1-chloro-1-
phenyl-1,2,2-trifluoroethane.7 The stereochemistry of the
resultant styrene was not reported. Dehydrofluorination
of 1-phenyl-1,1,2-trifluoroethane resulted in a low yield
of R,â-difluorostyrene; this dehydrofluorination was not
extended to other 1-aryl-1,1,2-trifluoroethanes.8 Low-
temperature metalation of several isomeric R,â-difluoro-
â-chlorostyrenes with an alkyllithium reagent, followed
by hydrolysis, has been reported to give predominantly
(E)-R,â-difluorostyrenes.9 Protodesilylation of (Z)-1,2-
difluoro-2-arylvinylsilanes by potassium fluoride in aque-
ous DMSO gave (E)-R,â-difluorostyrenes.10,11 In a recent
preliminary communication,12 we briefly described a
procedure for the preparation of (Z)-R,â-difluorostyrenes.
However, a general, stereoselective preparation of (E)-
R,â-difluoro-â-iodostyrenes has not been reported. Sev-
eral R,â-difluoro-â-iodostyrenes have been obtained by a
Hunsdiecker reaction of R,â-difluorocinnamic acid salts,
Resu lts a n d Discu ssion
Our recent development of (E) and (Z)-difluoroethene
synthons14 and our prior studies with fluorinated zinc
reagents15 prompted us to investigate a route to (Z)-R,â-
difluorostyrenes via the Pd(PPh3)4-catalyzed arylation of
(E)-HFCdCFZnI, 3. Vinylzinc reagent 3 was prepared
in two steps from 1, which is readily prepared from
bromotrifluoroethylene14 or chlorotrifluoroethylene.16 Io-
dodesilylation17 of 1 with KF/I2 gave a mixture of (E)-
HFCdCFI, 2, and Et3SiF (eq 1).
X Abstract published in Advance ACS Abstracts, December 1, 1997.
(1) Presented in part at the 15th International Symposium of
Fluorine Chemistry, Vancouver, B. C., Aug 1997.
(2) Current address: Department of Chemistry, Augustana College,
Rock Island, IL, 61201.
The mixture of Et3SiF and 2, after removal from the
reaction mixture under vacuum, was treated with acti-
vated zinc metal in DMF to give 3 (55-63%, based on 1,
as determined by internal PhCF3 standard) and 1,2-
difluoroethylene, 4 (eq 2). Zinc reagent 3 exhibits excel-
(3) Reynolds, D. W.; Cassidy, P. E.; J ohnson, C. G.; Cameron, M. L.
J . Org. Chem. 1990, 55, 4448-4454.
(4) Middleton, W. J .; Bingham, E. M. J . Fluorine Chem. 1983, 22,
561-574.
(5) .Middleton, W. J .; Metzger, D.; Snyder, J . A. J . Med. Chem. 1971,
14, 1193-1197.
(6) Sevestiyan, A. P.; Fialkov, Yu. A.; Khranovskii, V. A.; Yagupol-
skii, L. M. Zh. Org. Khim. 1978, 14, 204-205.
(7) Prober, M. J . Am. Chem. Soc. 1953, 75, 968-973.
(8) Leroy, J . J . Org. Chem. 1980, 46, 206-209.
(9) Martin, S.; Sauvetre, R.; Normant, J . F. Tetrahedron Lett. 1982,
23, 4329-4332.
(10) Yagupolskii, L. M.; Cherednichenko, P. G.; Kremlev, M. M. J .
Org. Chem. USSR (English Transl.) 1987, 23, 246-248.
(11) Martin, S.; Sauvetre, R.; Normant, J . F. Tetrahedron Lett. 1983,
24, 5615-5618.
(12) Davis, C. R.; Burton, D. J . Tetrahedron Lett. 1996, 37, 7237-
7240.
(13) Ling Xue, Ph.D. Thesis, University of Iowa, 1996; presented,
in part, at the 11th ACS Winter Fluorine Conference, Abstr. No. P56.
(14) Fontana, S. A.; Davis, C. R.; He, Y. H.; Burton, D. J . Tetrahe-
dron 1996, 52, 37-44.
(15) For a review, see: Burton, D. J .; Yang, Z. Y.; Morken, P. A.
Tetrahedron 1994, 50, 2993-3063.
(16) Hiyama, T.; Nishide, K.; Obayashi, M. Chem. Lett. 1984, 10,
1765-1768.
(17) Iododesilylation has been used extensively in our group to
prepare (E)- and (Z)-RCFdCFI from (E)- and (Z)-RCFdCFSiR3,
unpublished results, University of Iowa.
S0022-3263(97)01434-5 CCC: $14.00 © 1997 American Chemical Society

9218 J . Org. Chem., Vol. 62, No. 26, 1997
Davis and Burton
Ta ble 1. P d (P P h 3)4 Ca ta lyzed Ar yla tion of
Sch em e 1
(E)-HF CdCF Zn I
ArI
product
C6H5CFdCFH
no. yield (%)a
C6H5I
5
6
65
85
66b
78
72
93
71
60
80
70
55c
p-CH3OC6H4I
p-NO2C6H4I
o-NO2C6H4I
p-CH3C6H4I
p-EtO2CC6H4I
p-CH3C(O)C6H4I
m-ClC6H4I
p-CH3OC6H4CFdCFH
p-NO2C6H4CFdCFH
o-NO2C6H4CFdCFH
p-CH3C6H4CFdCFH
p-EtO2CC6H4CFdCFH
p-CH3C(O)C6H4CFdCFH
m-ClC6H4CFdCFH
7
8
9
10
11
12
1,4-C6H4I2
p-CF3C6H4I
p-HFCdCFC6H4CFdCFH 13
p-CF3C6H4CFdCFH 14
o-(CH3)2CHC6H4I o-(CH3)2CHC6H4CFdCFH 15
ArPdL2(CFdCFH) affords the styrene product and re-
generates Pd0L2.18,19
Although reaction of 3 with aryl iodides proceeds under
mild conditions, 3 did not undergo arylation with
p-CH3C6H4Br under similar conditions (12 h, room tem-
perature).
Reaction of 16 with 1.5 equiv of 3, however, gave a
mixture from which 13 was isolated, strongly suggesting
that aryl bromides containing electron-withdrawing groups
will undergo similar coupling (eq 4).
a
b
Isolated yield of (Z)-isomer only. Isolated as a 95:5 (Z:E)
mixture; reaction was carried out at 0 °C. c Reaction conditions:
60 °C, 8 h.
lent thermal stability. Significant loss of molarity, with
concomitant formation of 4, occurred only after extended
heating (12 h) at temperatures at or above 100 °C.
Treatment of 3 with HCl resulted in quantitative forma-
tion of 4 by 19F NMR analysis.
Substituted aromatic iodides coupled smoothly under
mild conditions with 3, in the presence of catalytic Pd-
(PPh3)4, to give (Z)-R,â-difluorostyrenes in good to excel-
lent yields (eq 3).
(Z)-R,â-Difluorostyrenes were readily converted to (E)-
R,â-difluoro-â-iodostyrenes in good yields. In one ap-
proach (method A), (Z)-R,â-difluorostyrenes, 18, were
treated with Li-2,2,6,6-tetramethylpiperidide (LTMP) at
-78 °C, and the resultant vinyllithium reagents were
trapped in situ with Bu3SnCl to form the vinylstannanes,
19 (Scheme 2). Subsequent cleavage of the tin moiety
with I2 gave the iodostyrenes, 20. Although vinylstan-
nanes 19a and 19b were isolated, the transformation was
amenable to a one-flask procedure. Reaction mixtures
containing the intermediate vinylstannanes 19c and 19d
were treated directly with I2 (entries 9 and 10, Table 2)
to give 27 and 28, respectively. The hindered LTMP base
was employed to hinder side reaction of the base with
Bu3SnCl. In a second approach (method B), the iodosty-
renes were directly prepared by low-temperature iodi-
nation of pregenerated vinyllithium reagents, 21 (Scheme
2). Method B is particularly convenient for preparation
of iodostyrenes containing functionalities compatible with
n-BuLi, as preparation of LTMP is not required and
separation of Bu3SnI is avoided. Our results utilizing
both approaches are summarized in Table 2.
Table 1 summarizes our results. The coupling reaction
was tolerant of a variety of functionalities; significant
differences in reaction time or yield were not observed
between electron-releasing and electron-withdrawing
groups. One exception was the reaction of p-NO2C6H4I
with 3 which gave 7 in reasonable yield when carried
out at 0 °C. Arylation of 3 with the sterically hindered
o-(CH3)2CHC6H4I substrate was optimized on heating.
p-Diiodobenzene coupled with 2 equivalents of 3 to give
the 1,4-disubstituted product 13. In each case, an excess
of 3 (1.3-1.5 equiv) was utilized to completely consume
the aryl iodide, thus avoiding a separation problem. In
no case was the minor (E)-R,â-difluorostyrene isomer
detected at a level above 5% of the product mixture.
Except for 7, the major (Z)-isomer was separated from
the (E)-isomer impurity by silica gel column chromatog-
raphy. The coupling reaction is proposed to proceed via
the following catalytic cycle (Scheme 1). Oxidative ad-
dition of ArI to Pd0L2 is followed by metathesis with
vinylzinc reagent 3; subsequent reductive elimination of
Although the vinyllithium reagents were successfully
trapped in situ with Bu3SnCl at -78 °C in method A,
method B was not attempted at -78 °C. As a minor
component of a (E/Z) mixture, (Z)-PhCFdCFLi has been
(18) Heinze, P. L.; Burton, D. J . J . Org. Chem. 1988, 53, 2714-
2720.
(19) Negishi, E. Acc. Chem. Res. 1982, 15, 340-348.

Stereoselective Preparation of (Z)-R,â-Difluorostyrenes
J . Org. Chem., Vol. 62, No. 26, 1997 9219
Ta ble 3. 19F NMR Da ta of (Z)-r,â-Diflu or ostyr en esa
Sch em e 2
no.
subst
a
b
J ab
J ac
J bc
5
6
7
8
9
10
11
12
13
14
15
H
-142.6
-140.9
-143.7
-145.8
-142.1
-143.7
-143.9
-142.9
-143.6
-143.7
-121.2
-164.8
-167.1
-157.3
-156.4
-166.1
-161.2
-160.6
-162.5
-162.9
-161.0
-159.4
11.8
12.8
9.8
17.0
14.9
16.0
12.9
15.9
15.7
16.9
16.9
16.7
16.9
17.8
73.2
73.4
71.2
71.9
73.2
71.9
72.0
71.9
72.3
71.8
74.3
p-CH3O
p-NO2
o-NO2
15.8
12.0
10.2
10.1
10.5
11.4
10.3
19.1
p-CH3
p-EtO2C
p-CH3C(O)
m-Cl
p-HFCdCF
p-CF3
b
o-(CH3)2CH
a
All spectra were recorded in CDCl3 and chemical shifts are
b
reported in ppm vs internal CFCl3 standard. p-CF3 appears at
-63.6 (s, 3F).
R,â-difluoro-â-iodostyrenes. Work aimed at utilizing the
resultant styrenes in the stereospecific construction of
functionalized fluorinated alkenes is in progress.
Ta ble 2. Con ver sion of (Z)-r,â-Diflu or ostyr en es to
(E)-r,â-Diflu or o-â-iod ostyr en es
Exp er im en ta l Section
Gen er a l. All glassware was oven-dried prior to use. 1H
NMR and {1H}13C NMR spectra were recorded at 300 MHz
and referenced against internal tetramethylsilane (TMS). 19F
NMR spectra were recorded at 300 or 90 MHz and referenced
vs internal CFCl3. GC-MS spectra were obtained at 70 eV in
the electron impact mode and reported as m/z (rel intens).
High-resolution mass spectral determinations were made at
the University of Iowa High-Resolution Mass Spectrometry
Facility. GLPC analyses were carried out on a 5% OV-101
column with a thermal conductivity detector.
Ma ter ia ls. DMF and DMSO were distilled from CaH2.
THF and Et2O were distilled from sodium benzophenone ketyl.
KF was dried by azeotropic distillation with benzene. Pd-
(PPh3)4 was prepared according to Coulson’s procedure.21
n-BuLi, 2,2,6,6-tetramethylpiperidine, and all aryl iodides were
obtained from commercial sources and used without further
purification.
entry
product
no.
method
yielda
1
2
3
4
5
6
7
8
9
p-CH3OC6H4CFdCFI
p-CH3OC6H4CFdCFI
C6H5CFdCFI
p-CH3C6H4CFdCFI
o-(CH3)2CHC6H4CFdCFI
p-CF3C6H4CFdCFI
p-CF3C6H4CFdCFI
p-EtO2CC6H4CFdCFI
p-EtO2CC6H4CFdCFI
m-ClC6H4CFdCFI
22
22
23
24
25
26
26
27
27
28
A
B
B
B
B
A
B
B
A
A
87
85
83
65
54
92b
81
39c
77d
85d
10
a
b
Isolated yields, based on ArCFdCFH. Product obtained as
a mixture containing Bu3SnI; an analytical sample of 26 (30%)
was obtained by chromatography. c LTMP substituted for n-BuLi.
P r ep a r a tion of (E)-HF CdCF Zn I (3). A 250 mL, three-
necked flask equipped with a magnetic stir bar, thermometer
adapter, coldfinger condenser set to -20 °C, and N2 source,
was charged with anhydrous KF (12.7 g, 219 mmol), I2 (38 g,
150 mmol), and 90 mL of DMSO. To the stirred mixture was
added (E)-HFCdCFSiEt3, 1 (13.0 g, 73 mmol, E:Z 95:5), via
syringe, in one portion. An exotherm resulted (60-70 °C)
followed by cooling to rt. The reaction mixture was stirred at
rt for an additional 36 h or until no starting material was
detected by 19F NMR analysis. The reaction flask was con-
nected to a liquid N2 cooled receiver and flash distilled (ca. 60
°C bath temperature, 10 mmHg). The contents of the reaction
flask were periodically analyzed by 19F NMR to determine
when all product had been removed from the reaction mixture.
The cooled receiver contained 2, Et3SiF, and DMSO. The
distillate was then redistilled through a short path apparatus
at atmospheric pressure, and a mixture of 2 and Et3SiF was
collected and used without further purification (bp 50-105 °C).
19F NMR for 2 (CDCl3) -106.5 (d, 3J F,H ) 15.2 Hz, 1 F), -130.7
d
One-flask procedure: the vinylstannane intermediate was
treated directly with I2.
reported to undergo decomposition at temperatures above
-85 °C whereas the major (E)-isomer exhibited thermal
stability up to -5 °C.9,20 The difference in stability is
presumably due to facile decomposition of (Z)-PhCFdCFLi
via an anti â-elimination pathway, unavailable to the (E)-
isomer, to give PhCtCF and LiF.9
The stereochemistry of both the (Z)-R,â-difluorosty-
renes and the (E)-R,â-difluoro-â-iodostyrenes was unam-
biguously assigned on the basis of 19F NMR coupling
constants. All products exhibited vicinal couplings (3J F,F
) 0-22 Hz) consistent with the cis-CFdCF stereochem-
istry vs the corresponding trans-CFdCF analogues (3J F,F
) 100-140 Hz).9,11 19F data for the (Z)-R,â-difluorosty-
renes is presented in Table 3. The (Z)-R,â-difluorosty-
renes and the (E)-R,â-difluoro-â-iodostyrenes, once puri-
fied, were stored for extended periods at 0-10 °C without
significant decomposition or detectable isomerization.
In conclusion, we have described a general method for
the stereoselective preparation of (Z)-R,â-difluorostyrenes
and for their subsequent stereospecific conversion to (E)-
2
(d, J F,H ) 75.2 Hz, 1 F).
A 50 mL flask equipped with a cold-water condenser,
magnetic stir bar, N2 source, and septum port, was charged
with acid-washed Zn metal (4.9 g, 75 mmol) and 30 mL of
DMF. A volume of 2/Et3SiF mixture (ca. 25 mmol) was added
via syringe in one portion. Induction occurred in 20-30 min
and an exotherm was observed. The remainder of the starting
material (25 mmol) was added dropwise, with the temperature
maintained at e60 °C. The dark-colored mixture was stirred
(20) Normant, J . F. J . Organomet. Chem. 1990, 400, 19-34.
(21) Coulson, D. R. Inorg. Synth. 1972, 13, 121-124.

9220 J . Org. Chem., Vol. 62, No. 26, 1997
Davis and Burton
an additional 45 min, and formation of 3 was confirmed by
19F NMR analysis of the reaction mixture (3:4 93:7). The
molarity of the vinylzinc reagent was determined by internal
PhCF3 standard. The excess Zn was allowed to settle, and
the solution was filtered through a coarse-fritted funnel and
the vinylzinc reagent was stored under N2 at rt. 19F NMR for
261.5, 15.2 Hz), 133.4, 131.5, 131.3, 125.0, 123.0 (dd, J ) 21.8,
3.8 Hz); GC-MS 185 (M+, 10), 138 (14), 127 (50), 119 (29), 109
(100), 107 (24), 101 (27), 99 (36), 89 (22), 63 (34); HRMS calcd
for C8H5F2NO2 185.0288, obsd 185.0272; FTIR (CCl4) 3117 (w),
1541 (s), 1338 (s), 1258 (w), 1142 (s), 1017 (m), 861 (w) cm-1
.
(Z)-p-CH3C6H4CF dCF H (9). According to the general
procedure, p-CH3C6H4I (1.75 g, 8.0 mmol), Pd(PPh3)4, and 3
(12 mmol) were stirred 2 h at rt. Following the standard
workup, the solvent was removed at atmospheric pressure.
Chromatography on SiO2 (pentane, Rf 0.4) gave 0.89 g (72%)
2
3 (DMF solution) -149.2 (d, J F,H ) 83 Hz, 1 F), -146.8 (d,
3J F,H ) 29 Hz, 1 F); 19F NMR for (Z)-HFCdCFH, 4 (DMF
2
3
solution) -164.2 (dd, J F,H ) 66 Hz, J F,H ) 32 Hz).
Gen er a l P r oced u r e for th e P r ep a r a tion of (Z)-r,â-
Diflu or ost yr en es. P r ep a r a t ion of (Z)-p -CO2E t C6H 4-
CF dCF H (10). A two-necked, 25 mL flask equipped with a
N2 source, magnetic stir bar, and rubber septum was charged
with Pd(PPh3)4 (0.29 g, 0.25 mmol, 3 mol %) and p-CO2EtC6H4I
(2.3 g, 8.3 mmol). A DMF solution of 3 (12 mmol) was added
via syringe, and the resultant mixture was stirred 2 h at rt.
The reaction mixture was diluted with cold water (75 mL) and
extracted with 1:1 pentane:Et2O (4 × 50 mL). The combined
extracts were dried (MgSO4) and concentrated by rotary
evaporation. Chromatography on SiO2 (80% pentane-EtOAc,
Rf 0.5) gave 1.63 g (93%) of 10 as a pale-yellow solid: mp 52-
53 °C; 1H NMR (CDCl3) δ 1.4 (t, 7.1 Hz, 3 H), 4.4 (q, 7.1 Hz, 2
H), 7.1 (dd, 72.5, 16.9 Hz, 1 H), 7.5 (d, 8.4 Hz, 2 H), 8.0 (d, 8.3
Hz, 2 H); 13C NMR (CDCl3) δ 14.3, 61.3, 123.2, (t, 4.2 Hz),
130.0, 131.2, 133.1 (d, 23.5 Hz), 135.4 (dd, 260.6, 15.1 Hz),
145.7 (dd, 247.5, 10.9 Hz), 165.8; FTIR (CCl4) 3122 (w), 2984
(w), 1724 (s), 1694 (s), 1411 (m), 1275 (s), 1146 (s), 1108 (s),
1013 (m) cm-1; HRMS calcd for C11H10F2O2 212.0649, obsd
212.0641.
1
of 9 as an oil: GLPC > 99%; H NMR (CDCl3) δ 2.3 (s, 3 H),
6.9 (dd, J ) 73.2, 17.2 Hz, 1 H), 7.1 (d, J ) 8.2 Hz, 2 H), 7.2
(d, J ) 8.2 Hz, 2 H); 13C NMR (CDCl3) δ 148.7 (dd, J ) 246.7,
10.8 Hz), 139.5 (d, J ) 3.8 Hz), 133.6 (dd, J ) 255.7, 15.9 Hz),
129.4, 127.0 (d, J ) 24.2 Hz), 123.6 (t, J ) 5.2 Hz), 21.1; GC-
MS 154 (M+, 100), 153 (65), 134 (17), 133 (59), 127 (14), 115
(6), 104 (10), 91 (6), 63 (11); HRMS calcd for C9H8F2 154.0594,
obsd 154.0585; FTIR (CCl4) 3122 (w), 3036 (w), 2924 (w), 1698
(s), 1542 (s), 1331 (s), 1291 (m), 1137 (s), 1012 (s) cm-1
(Z)-p-CH3(CO)C6H4CF dCF H (11). According to the gen-
eral procedure, p-CH3C(O)C6H4I (1.85 g, 7.5 mmol), Pd(PPh3)4,
and 3 (11 mmol) were stirred 3 h at rt. Following the standard
workup, chromatography on SiO2 (90% pentane-EtOAc, Rf 0.2)
gave 0.97 g (71%) of 11 as a pale-yellow solid: mp 48-49 °C;
1H NMR (CDCl3) δ 2.6 (s, 3 H), 7.1 (dd, J ) 72.5, 16.9 Hz, 1
H), 7.5 (d, J ) 8.4 Hz, 2 H), 7.9 (d, 8.4 Hz, 2 H); 13C NMR
(CDCl3) δ 197.0, 147.5 (dd, J ) 247.6, 11.0 Hz), 137.4 (d, J )
2.3 Hz), 135.5 (dd, J ) 261.2, 15.1 Hz), 133.2 (d, J ) 23.4 Hz),
123.3 (t, J ) 5.5 Hz), 128.7, 26.4; GC-MS 182 (M+, 35), 167
(100), 139 (36), 119 (52), 99 (14), 63 (9), 43 (28); HRMS calcd
for C10H8F2O 182.0543, obsd 182.0545; FTIR (CCl4) 3122 (w),
(Z)-C6H5CF dCF H (5). According to the general procedure,
C6H5I (1.63 g, 8.0 mmol), Pd(PPh3)4, and 3 (12 mmol) were
stirred 2 h at rt. Following the standard workup, the solvent
was removed at atmospheric pressure. Chromatography on
SiO2 (pentane, Rf 0.4) gave 0.73 g (65%) of 5 as an oil: GLPC
> 99%; 1H NMR (CDCl3) δ 6.9 (dd, J ) 72.9, 17.1 Hz, 1 H), 7.4
(m, 5 H); 13C NMR (CDCl3) δ 148.5 (dd, 247.0, 10.2 Hz), 134.1
(dd, J ) 256.7, 15.6 Hz), 129.3, 129.0, 128.7, 123.6 (J ) t, 5.5
Hz); GC-MS 140 (M+, 100), 139 (26), 120 (17), 119 (18), 114
(26), 101 (13), 89 (13), 63 (18), 51 (17); HRMS calcd for C8H6F2
140.0438, obsd 140.0430; FTIR (CCl4) 3120 (w), 3066 (w), 1697
1691 (s), 1609 (m), 1359 (m), 1267 (s), 1148 (s), 1011 (m) cm-1
.
(Z)-m -ClC6H4CF dCF H (12). According to the general
procedure, m-ClC6H4I (1.55 g, 6.5 mmol), Pd(PPh3)4, and 3 (9
mmol) were stirred 2 h at rt. Following the standard workup,
the solvent was removed at atmospheric pressure. Chroma-
tography on SiO2 (pentane, Rf 0.4) gave 0.68 g (60%) of 12 as
an oil: GLPC > 99%; 1H NMR (CDCl3) δ 7.0 (dd, J ) 71.9,
16.9 Hz, 1 H), 7.2-7.4 (m, 4 H); 13C NMR (CDCl3) δ 147.5 (dd,
J ) 247.8, 11.0 Hz), 134.8 (dd, J ) 259.3, 15.1 Hz), 135.0, 130.8
(d, J ) 23.9 Hz), 130.2, 123.8 (t, J ) 4.7 Hz), 129.5, 121.7 (t,
J ) 4.2 Hz); GC-MS 174 (M+, 100) 176 (M+, 32) 139 (56), 138
(16), 120 (10), 119 (48), 99 (11), 63 (7); HRMS calcd for C8H5-
35ClF2 174.0048, obsd 174.0063; FTIR (CCl4) 3126 (w), 1698
(s), 1335 (s), 1292 (m), 1142 (s), 1041 (s), 837 (s) cm-1
.
(Z)-p-CH3OC6H4CF dCF H (6). According to the general
procedure, p-CH3OC6H4I (4.2 g, 18.0 mmol), Pd(PPh3)4, and 3
(25 mmol) were stirred 2 h at rt. Following the standard
workup, chromatography on SiO2 (85% pentane-EtOAc, Rf
0.6) gave 2.6 g (85%) of 6 as a low-melting solid: GLPC 96%;
1H NMR (CDCl3) δ 3.8 (s, 3 H), 6.8 (dd, J ) 73.4, 17.3 Hz, 1
H), 6.9 (d, J ) 8.7 Hz, 2 H), 7.3 (d, J ) 8.7 Hz, 2 H); 13C NMR
(CDCl3) δ 160.7, 148.7 (dd, J ) 246.3, 10.0 Hz), 133.2 (dd, J )
254.3, 16.3 Hz), 125.6 (t, J ) 4.5 Hz), 121.3 (d, J ) 24.4 Hz),
114.3, 55.3; GC-MS 170 (M+, 100) 171 (10), 155 (55), 127 (67),
101 (15); HRMS calcd for C9H8F2O 170.0543, obsd 170.0543;
FTIR (CCl4) 2959 (w), 2839 (w), 1699 (m), 1610 (s), 1252 (s),
(m), 1566 (s), 1327 (w), 1148 (m), 1038 (m) cm-1
.
(Z,Z)-p-(HF CdCF )C6H4(CF dCF H) (13). According to the
general procedure, p-C6H4I2 (1.65 g, 5.0 mmol), Pd(PPh3)4, and
3 (15 mmol) were stirred 2 h at rt. Following the standard
workup, chromatography on SiO2 (95% pentane-EtOAc, Rf
0.4) gave 0.81 g (80%) of 13 as a yellow solid: mp 41-42 °C;
1H NMR (CDCl3) δ 7.0 (dd, J ) 72.3, 17.1 Hz, 2 H), 7.4 (s, 4
H); 13C NMR (CDCl3) δ 147.9 (dd, J ) 246.9, 11.0 Hz), 134.6
(dd, J ) 259.2, 15.4 Hz), 129.7 (d, 24.0 Hz), 123.8 (t, J ) 3.8
Hz); GC-MS 202 (M+, 100), 200 (7), 183 (5), 182 (20), 151 (36),
133 (9), 114 (3); HRMS calcd for C10H6F4 202.0406, obsd
202.0408; FTIR (CCl4) 3122 (w), 1696 (s), 1413 (w), 1339 (m),
1138 (s), 1023 (s), 820 (m) cm-1
.
(Z)-p-NO2C6H4CF dCF H (7). According to the general
procedure, p-NO2C6H4I (1.25 g, 5.0 mmol), Pd(PPh3)4, and 3
(7.5 mmol) were stirred 1 h at 0 °C and 3 h at rt. Following
the standard workup, chromatography on SiO2 (85% hexanes-
EtOAc, Rf 0.4) gave 0.62 g (66%) of 7 as a yellow solid: mp
78-79 °C; 1H NMR (CDCl3) δ 7.2 (dd, J ) 71.2, 16.7 Hz, 1 H),
7.6 (d, J ) 8.9 Hz, 2 H), 8.3 (d, J ) 8.7 Hz, 2 H); 13C NMR
(CDCl3) δ 148.2, 147.0 (dd, J ) 248.0, 11.9 Hz), 136.4 (dd, J )
264.3, 14.9 Hz), 135.2 (d, J ) 23.9 Hz), 124.2, 124.1 (t, J ) 4.5
Hz); GC-MS 185 (M+, 100), 155 (36), 139 (13), 138 (17), 127
(37), 119 (77), 99 (44), 88 (16), 63 (31); HRMS calcd for C8H5F2-
NO2 185.0288, obsd 185.0295; FTIR (CCl4) 3122 (w), 2927 (w),
2856 (w), 1693 (m), 1528 (s), 1337 (s), 1151 (s), 1020 (m), 870
1296 (w), 1146 (s), 1040 (s), 1009 (m), 840 (m) cm-1
.
P r ep a r a tion of 13 by Rea ction of 3 a n d p-Br C6H4I, 16.
According to the general procedure, 16 (1.43 g, 5.0 mmol), Pd-
(PPh3)4, and 3 (10 mmol) were stirred 8 h at rt. Following the
standard workup, chromatography on SiO2 (85% pentane-
EtOAc, Rf 13 0.6, Rf 17 0.7) gave 0.33 g (33%) of 13 (mp 41-
42 °C) and 0.17 g of a mixture containing 17 and 13 (17:13
1:1). Data for 17: 19F NMR (CDCl3) δ -143.1 (dd, 17.6, 10.6
1
Hz, 1 F), -163.4 (dd, 72.4, 11.9 Hz, 1 F); H NMR (CDCl3) δ
6.9 (dd, 72.4, 17.0 Hz, 1 H), 7.2 (d, 8.6 Hz, 2 H), 7.5 (d, 8.4 Hz,
2 H); GC-MS 220 (M+, 95.4), 218 (M+, 100), 139 (38.4), 138
(18.6), 120 (16.6), 119 (84.7), 99 (26.5), 88 (11.0), 63 (10.1), 50
(11.9).
(m) cm-1
.
(Z)-o-NO2C6H4CF dCF H (8). According to the general
procedure, o-NO2C6H4I (1.25 g, 5.0 mmol), Pd(PPh3)4, and 3
(7.5 mmol) were stirred 2 h at rt. Following the standard
workup, chromatography on SiO2 (CH2Cl2, Rf 0.75) gave 0.72
g (78%) of 8 as a yellow-orange solid: mp 69-70 °C; 1H NMR
(CDCl3) δ 6.8 (dd, J ) 71.9, 15.8 Hz, 1 H), 7.5 (d, J ) 7.0 Hz,
1 H), 7.7 (m, 2 H), 8.0 (dd, J ) 7.3, 1.8 Hz, 1 H); 13C NMR
(CDCl3) δ 147.9, 145.8 (dd, J ) 251.5, 12.9 Hz), 135.4 (dd, J )
(Z)-p-CF 3C6H4CF dCF H (14). According to the general
procedure, p-CF3C6H4I (3.2 g, 11.7 mmol), Pd(PPh3)4, and 3
(17 mmol) were stirred 2 h at rt. Following the standard
workup, the solvent was removed at atmospheric pressure.
Chromatography on SiO2 (95% pentane-CH2Cl2, Rf 0.6) gave
1.7 g (70%) of 14 as an oil: GLPC 99%; 1H NMR (CDCl3) δ 7.1
(dd, J ) 71.8, 16.9 Hz, 1 H), 7.5 (d, J ) 8.4 Hz, 2 H), 7.6 (d, J

Stereoselective Preparation of (Z)-R,â-Difluorostyrenes
J . Org. Chem., Vol. 62, No. 26, 1997 9221
) 8.4 Hz, 2 H); 13C NMR (CDCl3) δ 147.5 (dd, J ) 247.7, 11.1
Hz), 135.3 (dd, J ) 260.8, 15.0 Hz), 132.5 (d, J ) 24.1 Hz),
131.3 (q, J ) 33.5 Hz), 125.8, 123.5 (q, J ) 272.2 Hz), 123.7 (t,
J ) 5.5 Hz); GC-MS 208 (M+, 100), 189 (27), 187 (11), 169 (13),
158 (28), 139 (34), 138 (15), 119 (22), 63 (6); HRMS calcd for
C9H5F5 208.0311, obsd 208.0289; FTIR (CCl4) 3123 (w), 1696
with 3:2 THF:Et2O (30 mL) and 6 (1.25 g, 7.35 mmol) and
cooled to -100 °C via liquid N2/pentane bath. n-BuLi (9.6
mmol, 2.5 M in hexanes) was added dropwise via syringe at
-95 to -100 °C. After addition was complete, the solution
was stirred 30 min at -100 °C. A solution of I2 (2.8 g, 11 mmol,
in 15 mL THF) was added dropwise at -100 °C. The resultant
solution was stirred an additional 30 min at -100 °C and
allowed to warm to -20 °C. Dilute HCl (2 mL) was added
dropwise and the solution was allowed to warm to rt. The
mixture was poured into saturated aq NaHSO3 (50 mL) and
extracted with Et2O (3 × 75 mL). The Et2O fractions were
dried (MgSO4) and concentrated by rotary evaporation. Chro-
matography on SiO2 (80% hexanes-EtOAc, Rf 0.4) gave 1.75
g (85%) of 22: GLPC > 99%.
(m), 1622 (w), 1334 (s), 1163 (s), 1070 (w), 1020 (m) cm-1
.
(Z)-o-(CH3)2CHC6H4CF dCF H (15). According to the gen-
eral procedure, o-(CH3)2CHC6H4I (2.46 g, 10.0 mmol), Pd-
(PPh3)4, and 3 (15 mmol) were stirred 8 h at 60 °C. Following
the standard workup, chromatography on SiO2 (pentane, Rf
1
0.5) gave 1.0 g (55%) of 15 as an oil: GLPC > 99%; H NMR
(CDCl3) δ 3.2 (septet of doublets, J ) 6.8, 2.8 Hz, 1 H), 1.2 (d,
J ) 6.8 Hz, 6 H), 6.5 (dd, J ) 74.3, 16.2 Hz, 1 H), 7.1-7.3 (m,
2 H), 7.3-7.4 (m, 2 H); 13C NMR (CDCl3) δ 149.8 (d, J ) 4.2
Hz), 148.0 (dd, J ) 253.2, 9.4 H), 135.0 (dd, J ) 258.5, 17.0
Hz), 131.0 (d, J ) 1.8 Hz), 130.6 (t, J ) 2.4 Hz), 126.7 (dd, J
) 20.7, 1.8 Hz), 126.0 (d, J ) 1.5 Hz), 125.7, 30.5 (d, J ) 2.3
Hz), 24.0; FTIR (CCl4) 2967 (m), 1709 (m), 1559 (s), 1449 (w),
1320 (m), 1131 (m), 1011 (m), 826 (w) cm-1; GC-MS 182 (M+,
12), 167 (100), 149 (13), 147 (85), 146 (48), 133 (23), 129 (34),
128 (13), 127 (37), 115 (18); HRMS calcd for C11H12F2 182.0907,
obsd 182.0893.
(E)-C6H5CF dCF I (23). Meth od B. Preparation of 23 was
carried out according to the general procedure using 5 (0.55
g, 3.9 mmol), 1:1 THF:Et2
O (30 mL), n-BuLi (5.1 mmol), and
I2 (1.6 g, 6.2 mmol). Following the standard workup, chro-
matography on SiO2 (pentane, Rf 0.4) gave 0.86 g (83%) of 23
as an oil: GLPC > 98%; 19F NMR (CDCl3) δ -101.1 (d, J )
1
5.1 Hz, 1 F), -109.0 (d, J ) 5.1 Hz, 1 F); H NMR (CDCl3) δ
7.4 (m, 3 H), 7.6 (m, 2 H);
13C NMR (CDCl3) δ 147.9 (dd, J )
257.0, 12.8 Hz), 130.3, 128.8 (d, J ) 7.0 Hz), 128.7, 128.3, 96.1
(dd, J ) 362.2, 33.6 Hz); GC-MS 266 (M+, 100.0), 140 (3.3),
139 (33.3), 138 (11.3), 127 (5.1), 119 (35.8), 99 (14.4), 75 (3.7),
63 (7.1); FTIR (CCl4) 3063 (w), 1653 (m), 1495 (w), 1446 (w),
Gen er a l P r oced u r e for Con ver sion of (Z)-r,â-Diflu o-
r ostyr en es to (E)-r,â-Diflu or o-â-iod ostyr en es. P r ep a r a -
tion of (E)-p-MeOC6H4CF dCF I (22). Meth od A. A three-
necked, 50 mL flask equipped with a magnetic stir bar, N2
source, low-temperature thermometer adapter, and septum
port was charged with THF (20 mL) and 2,2,6,6-tetrameth-
ylpiperidine (1.2 g, 8.1 mmol). The solution was cooled to -20
°C via dry ice/IPA bath. n-BuLi (8.1 mmol, 2.5 M in hexanes)
was added dropwise at e0 °C. The resultant LTMP solution
was stirred an additional 5 min at 0 °C. A 50 mL, three-
necked flask equipped with a low-temperature thermometer
adapter, N2 source, magnetic stir bar, and septum port was
charged with 6 (1.05 g, 6.27 mmol), THF (20 mL), and Bu3-
SnCl (2.6 g, 7.9 mmol). The solution was cooled to -78 °C via
dry ice/IPA bath. The LTMP base solution was added drop-
wise via syringe at -78 °C. After addition was complete, the
solution was stirred at -78 °C for 1 h and allowed to warm to
rt. The mixture was poured into water (75 mL) and extracted
with Et2O (3 × 75 mL). The Et2O fractions were dried (MgSO4)
and concentrated by rotary evaporation. Chromatography on
SiO2 (85% hexanes-EtOAc, Rf 0.6) gave 2.77 g (95%) of (E)-
p-MeOC6H4CFdCFSnBu3, 19a , as an oil: 19F NMR (CDCl3) δ
-109.7 (d, J ) 5.6 Hz, 1 F), -140.6 (d, J ) 5.6 Hz, 1 F), -140.6
(dd J FSn ) 168.5 Hz, J FF ) 5.6 Hz; 1H NMR (CDCl3) δ 0.9-1.5
(m, 27 H), 3.8 (s, 3 H), 6.9 (d, J ) 9.0 Hz, 2 H), 7.3 (d, J ) 9.0
Hz, 2 H); 13C NMR (CDCl3) δ 160.9, 155.4 (dd, J ) 258.9, 11.1
Hz), 153.2 (d, J ) 308.0 Hz), 129.9, 123.3 (dd, J ) 26.1, 3.2
Hz), 113.9, 55.3, 28.8, 28.8 (d, J CSn ) 23 Hz), 27.2, 27.2 (d,
J CSn ) 64 Hz), 13.6, 10.8, 10.8 (d, J CSn ) 362 Hz); FTIR (CCl4)
2958 (s), 2926 (s), 2873 (m), 1643 (w), 1609 (m), 1512 (s), 1458
(m), 1250 (s), 1030 (s) cm-1; GC-MS 403 (M+ - C4H8, 35), 401
(27), 399 (16), 253 (67), 251 (54), 249 (33), 177 (60), 159 (83),
150 (100), 135 (70), 107 (57), 57 (60). A two-necked, 25 mL
flask equipped with a magnetic stir bar, N2 source, and septum
port was charged with I2 (2.1 g, 8.0 mmol) and DMF (15 mL).
A solution of vinylstannane 19a (2.3 g, 5.0 mmol, in 5 mL
DMF) was added in one portion via syringe, and the mixture
was stirred 1 h at rt. The mixture was diluted with hexane
(250 mL) and washed with saturated aq NaHSO3 (75 mL). The
hexane fraction was dried (MgSO4) and concentrated by rotary
evaporation. Chromatography on SiO2 (85% hexanes-EtOAc,
Rf 0.4) gave 1.35 g (87%, based on 6) of 22 as a clear oil: GLPC
g 99%; 19F NMR (CDCl3) δ -102.9 (bs, 1 F), -107.6 (bs, 1 F);
1H NMR (CDCl3) δ 3.8 (s, 3 H), 6.9 (d, J ) 8.9 Hz, 2 H), 7.5 (d,
J ) 8.9 Hz, 2 H); 13C NMR (CDCl3) δ 160.9, 147.8 (dd, J )
256.7, 13.0 Hz), 130.4, 120.5 (d, J ) 24.5 Hz), 113.7, 95.2 (dd,
J ) 325.8, 34.4 Hz), 55.3; GC-MS 296 (M+, 77), 281 (18), 169
(12), 154 (54), 126 (100), 107 (20), 101 (16), 75 (21), 62 (17);
HRMS calcd for C9H7OF2I 295.9510, obsd 295.9505; FTIR
(CCl4) 2960 (w), 2841 (w), 1610 (s), 1513 (s), 1255 (s), 1033 (s),
1302 (m), 1280 (m), 1130 (s), 1057 (s), 1025 (m), 884 (s) cm-1
HRMS calcd for C8H5F2I 265.9404, obsd 265.9391.
;
(E)-p-CH3C6H4CF dCF I (24). Meth od B. Preparation of
24 was carried out according to the general procedure using 9
(2.3 g, 14.9 mmol), 3:2 THF:Et2O (50 mL), n-BuLi (19.5 mmol),
and I2 (6.1 g, 24 mmol). Following the standard workup,
chromatography on SiO2 (pentane, Rf 0.4) gave 2.7 g (65%) of
24 as an oil: GLPC > 98%; 19F NMR (CDCl3) δ -102.2 (d, J
) 4.2 Hz, 1 F), -108.6 (d, J ) 4.2 Hz, 1 F); 1H NMR CDCl3) δ
2.4 (s, 3 H), 7.2 (d, J ) 8.0 Hz, 2 H), 7.5 (d, J ) 8.2 Hz, 2 H);
13C NMR (CDCl3) δ 148.0 (dd, J ) 256.6, 12.8 Hz), 140.6, 129.0,
128.7 (t, J ) 3.4 Hz), 125.7 (d, J ) 24.0 Hz), 95.7 (dd, J )
325.9, 34.2 Hz), 21.4; FTIR (CCl4) 3036 (w), 2925 (w), 1657
(m), 1612 (m), 1514 (m), 1300 (s), 1130 (s), 1052 (s), 886 (s)
cm-1; GC-MS 280 (M+, 100.0), 153 (20.6), 151 (35.9), 138 (13.1),
133 (79.4), 127 (31.9), 125 (52.2), 107 (9.1), 101 (7.5), 75 (10.3);
HRMS calcd for C9H7F2I 279.9561, obsd 279.9587.
(E)-o-(CH3)2CHC6H4CF dCF I (25). Meth od B. Prepara-
tion of 25 was carried out according to the general procedure
using 15 (0.75 g, 4.1 mmol), 1:1 THF:Et2O (20 mL), n-BuLi
(5.3 mmol), and I2 (1.7 g, 6.6 mmol). Following the standard
workup, chromatography on SiO2 (pentane, Rf 0.5) gave 0.67
g (54%) of 25 as an oil: GLPC 98%; 19F NMR (CDCl3) δ -98.1
(bs, 1 F), -103.5 (bs, 1 F); 1H NMR (CDCl3) 1.2 (d, J ) 7.0 Hz,
6 H), 3.1 (septet of doublets, J ) 2.5 Hz, 1 H), 7.1-7.5 (m, 4
H);
13C NMR (CDCl3) δ 149.8 (d, J ) 3.4 Hz), 147.5 (dd, J )
263.0, 11.0 Hz), 132.0 (dd, J ) 3.4, 1.2 Hz), 131.5 (d, J ) 3.0
Hz), 98.6 (dd, J ) 329.6, 33.6 Hz), 127.5 (d, J ) 21.0 Hz), 126.5
(d, J ) 12.5 Hz), 126.0 (dd, J ) 4.5, 2.1 Hz), 30.9, 24.0; FTIR
(CCl4
) 2967 (s), 2871 (w), 1676 (m), 1457 (m), 1295 (s), 1267
(m) 1128 (s), 1026 (s), 872 (s) cm-1; GC-MS 308 (M+, 8.7), 181
(44.1), 166 (19.5), 165 (23.3), 164 (19.5), 151 (49.3), 146 (100.0),
133 (28.7), 115 (29.2); HRMS calcd for C11H11F2I 307.9874, obsd
307.9862.
(E)-p-CF 3C6H4CF dCF I (26). Meth od A. Preparation of
26 was carried out according to the general procedure using
14 (1.7 g, 8.2 mmol), Bu3SnCl (3.25 g, 10.0 mmol), THF (25
mL), and a solution of LTMP prepared from 2,2,6,6-tetram-
ethylpiperidine (1.50 g, 10.4 mmol), n-BuLi (10.4 mmol), and
THF (20 mL). Following the standard workup, chromatogra-
phy on SiO2 (85% hexanes-EtOAc, Rf 0.7) gave 3.9 g (96%) of
(E)-p-CF3C6H4CFdCFSnBu3, 19b, as an oil: 19F NMR (CDCl3)
δ -135.0 (bs, 1 F), -135.0 (d, J FSn ) 192 Hz), -115.5 (bs, 1 F),
-64.6 (s, 3 F); 1H NMR (CDCl3) δ 0.8-1.5 (m, 27 H), 7.5 (d, J
) 8.2 Hz, 2 H), 7.6 (d, J ) 8.2 Hz, 2 H); 13C NMR (CDCl3) δ
156.4 (d, J ) 312.0 Hz), 154.6 (dd, J ) 269.0, 12.3 Hz), 134.7
(d, J ) 26.9 Hz), 131.6 (q, J ) 32.9 Hz), 127.8 (t, J ) 3.2 Hz),
766 (s) cm-1
.
125.5 (q, J ) 3.6 Hz), 123.9 (q, J ) 271.7 Hz), 28.9 (d, J CSn
)
Meth od B. A three-necked, 50 mL flask equipped with a
magnetic stir bar, N2 source, and septum port was charged
22 Hz), 27.2 (d, J CSn ) 54 Hz), 13.6, 11.0 (d, J CSn ) 366 Hz);
FTIR (CCl4) 2960 (s), 2926 (s), 2855 (m), 1326 (s), 1173 (m),

9222 J . Org. Chem., Vol. 62, No. 26, 1997
Davis and Burton
1137 (m), 1070 (s), 847 (m) cm-1. Conversion of 19b to 26 was
carried out using 19b (3.9 g, 7.85 mmol), I2 (3.20 g, 12.6 mmol),
and DMF (20 mL). Following analogous workup, the residue
was twice chromatographed on SiO2 (pentane, Rf 0.5) to give
3.0 g of an oil containing 26 and Bu3SnI (26:Bu3SnI 1.6:1.0)
and an additional 0.83 g (30%) of 26 as an analytically pure
sample: GLPC > 99%; 19F NMR (CDCl3) δ -63.6 (s, 3 F),
-97.5 (d, J ) 4.2 Hz, 1 F), -111.0 (d, J ) 4.2 Hz, 1 F); 1H
NMR (CDCl3) δ 7.7 (d, J ) 8.3 Hz, 2 H), 7.8 (d, J ) 8.3 Hz, 2
H ); 13C NMR (CDCl3) δ 146.9 (dd, J ) 257, 14 Hz), 132.4 (d,
J ) 23 Hz), 132.3 (q, J ) 32.8 Hz), 129.0 (t, J ) 3.5 Hz), 125.5
(q, J ) 1.9 Hz), 123.7 (q, J ) 272 Hz), 97.4 (dd, J ) 328, 32
Hz); GC-MS 334 (M+, 58), 315 (6), 207 (35), 133 (13), 187 (67),
156 (11), 142 (17), 138 (100), 69 (13); HRMS calcd for C9H4F5I
333.9278, obsd 333.9283; FTIR (CCl4) 2959 (m), 2928 (m), 2860
Meth od B. Preparation of 27 was carried out according to
the general procedure using 10 (1.04 g, 4.95 mmol), 3:2 THF:
Et2O (30 mL), a solution of LTMP prepared from 2,2,6,6-
tetramethylpiperidine (0.88 g, 6.2 mmol) and n-BuLi (6.2
mmol) in 10 mL of THF, and I2 (2.0 g, 8.0 mmol). Following
the standard workup, chromatography on SiO2 (75% hexanes-
EtOAc, Rf 0.5) gave 0.56 g (39%) of 27.
(E)-m -ClC6H4CF dCF I (28). Meth od A. Preparation of
28 was carried out according to the general procedure using
12 (0.39 g, 2.24 mmol), 3:2 THF:Et2O (30 mL), Bu3SnCl (0.93
g, 2.86 mmol), and a solution of LTMP prepared from 2,2,6,6-
tetramethylpiperidine (0.41 g, 2.9 mmol) and n-BuLi (2.9
mmol) in 10 mL of THF. The reaction mixture containing the
intermediate (E)-m-ClC6H4CFdCFSnBu3, 19d , was treated
directly with I2 (1.4 g, 5.5 mmol) at rt and stirred overnight.
Following the standard workup, chromatography on SiO2
(hexane, Rf 0.5) gave 0.56 g (85%) of 28 as an oil: GLPC 93%;
19F NMR (CDCl3) δ -98.7 (d, J ) 5.1 Hz, 1 F), -110.1 (d, J )
(w), 1326 (s) 1175 (s), 1138 (s), 1074 (s), 886 (m) cm-1
.
Meth od B. Preparation of 26 was carried out according to
the general procedure using 14 (1.37 g, 6.6 mmol), 1:1 THF:
Et2O (50 mL), n-BuLi (8.6 mmol), and I2 (2.7 g, 10.6 mmol).
Following the standard workup, chromatography on SiO2
(pentane, Rf 0.5) gave 1.78 g (81%) of 26: GLPC > 99%.
(E)-p-CO2EtC6H4CF dCF I (27). Meth od A. Preparation
of 27 was carried out according to the general procedure using
10 (1.21 g, 5.7 mmol), THF (25 mL), Bu3SnCl (2.3 g, 7.1 mmol),
and a solution of LTMP prepared from 2,2,6,6-tetramethylpi-
peridine (1.05 g, 7.4 mmol) and n-BuLi (7.5 mmol) in 10 mL
of THF. The reaction mixture containing the intermediate (E)-
p-CO2EtC6H4CFdCFSnBu3, 19c, was treated directly with I2
(2.3 g, 9.1 mmol) at rt and stirred overnight. Following the
standard workup, chromatography on SiO2 (80% hexanes-
EtOAc, Rf 0.45) gave 1.49 g (77%) of 27 as yellow-orange
solid: mp 44 °C; 19F NMR (CDCl3) δ -97.7 (d, J ) 5.7 Hz, 1
F), -111.1 (d, J ) 5.7 Hz, 1 F); 1H NMR (CDCl3) δ 8.1 (d, J )
8.1 Hz, 2 H), 7.7 (d, J ) 8.3 Hz, 2 H), 4.4 (q, J ) 7.0 Hz, 2 H),
1.4 (t, J ) 7.0 Hz, 3 H); 13C NMR (CDCl3) δ 165.5, 147.2 (dd,
J ) 256.3, 13.8 Hz), 132.5 (d, J ) 23.8 Hz), 131.8, 129.4, 128.4
(t, J ) 3.3 Hz), 97.1 (dd, J ) 328.1, 32.4 Hz), 61.3, 14.2; GC-
MS 338 (M+, 47.4), 310 (31.9), 293 (100.0), 265 (9.9), 183 (3.2),
138 (81.0), 119 (14.0), 112 (10.5), 88 (17.5), 87 (14.3); FTIR
(CCl4) 2983 (m), 2961 (m), 2931 (m), 1726 (s), 1408 (w), 1276
(s), 1108 (s), 1054 (s), 888 (m) cm-1; HRMS calcd for C11H9F2-
IO2 337.9615, obsd 337.9611.
1
5.1 Hz, 1 F); H NMR (CDCl3) δ 7.3-7.4 (m, 2 H), 7.5 (m, 1
H), 7.6 (m, 1 H); 13C NMR (CDCl3) δ 146.7 (dd, J ) 256.9, 13.7
Hz), 140.2, 134.4, 130.3, 129.6, 128.6 (t, J ) 3.6 Hz), 126.8 (t,
J ) 3.4 Hz), 96.8 (dd, J ) 328.1, 33.0 Hz); FTIR (CCl4) 3072
(w), 1653 (w), 1558 (s), 1479 (w), 1415 (w), 1286 (m), 1134 (s),
1062 (s), 906 (s) cm-1; GC-MS 300 (M+, 64.4), 302 (M+, 21.5),
173 (31.3), 175 (10.5), 139 (9.4), 138 (100.0), 127 (9.1), 118 (6.3),
88 (7.8), 87 (15.1).
Ack n ow led gm en t. We would like to thank the
National Science Foundation for financial support of this
work.
Su p p or tin g In for m a tion Ava ila ble: Copies of NMR
spectra for compounds 5-15, 17, and 22-28 (42 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.
J O971434O