Coupling of 2-substituted 1-fluorovinylstannanes with organic halides catalyzed by palladium(0)/copper(I) iodide. A mild and stereospecific method to monofluoroolefins

Article abstract of DOI:10.1021/jo982200n

The palladium-catalyzed cross-coupling reactions of (E)- or (Z)-1- fluorovinylstannanes with aryl iodides and vinyl iodides provide good yields of stereoisomerically pure substituted fluoroolefins with retention of the double bond geometry. The reaction t

Full text of DOI:10.1021/jo982200n

3
476
J . Org. Chem. 1999, 64, 3476-3482
Cou p lin g of 2-Su bstitu ted 1-F lu or ovin ylsta n n a n es w ith Or ga n ic
Ha lid es Ca ta lyzed by P a lla d iu m (0)/Cop p er (I) Iod id e. A Mild a n d
Ster eosp ecific Meth od to Mon oflu or oolefin s
Chen Chen,* Keith Wilcoxen, Yun-Fei Zhu, Kyung-il Kim, and J ames R. McCarthy*
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 10555 Science Center Drive,
San Diego, California 92121
Received November 2, 1998
The palladium-catalyzed cross-coupling reactions of (E)- or (Z)-1-fluorovinylstannanes with aryl
iodides and vinyl iodides provide good yields of stereoisomerically pure substituted fluoroolefins
with retention of the double bond geometry. The reaction takes place with copper(I) iodide present
as a cocatalyst at ambient temperature or in refluxing tetrahydrofuran and is tolerant of a variety
of functional groups. Highly functionalized and stereoisomerically pure monofluorovinyl ketones
also were obtained under mild conditions by the coupling of 1-fluorovinylstannanes with acid
1
19
chlorides. H-{ F} NOE NMR experiments unequivocally established the stereochemistry of the
coupling products E-14 and Z-14.
In tr od u ction
of the somewhat capricious trimethylsilyl group.7 It
should be noted that 1-fluorovinylstannane enol ethers
have proved useful for the synthesis of monoofluorovinyl
There has been considerable interest in fluoroorganic
compounds as agrochemical and pharmaceutical agents.1
It is believed that fluorine alters the physiochemical
properties of organic compounds, thereby modifying
8
ethers as well. Shi and co-workers reported the synthesis
of â-fluorophenylalanine via palladium-catalyzed cross-
coupling of ethyl 3-fluoro-3-tributylstannyl-2-methoxy-
acrylate (1c) with aryl iodides or triflates. Percy and
2
biological activity. This has been particularly true for
olefins, and new methods for the synthesis of fluoroolefins
have received considerable attention. The use of 1-fluo-
9
Wilkes demonstrated in an informative paper the utility
3
of 1-lithio-1-fluorovinyl enol ethers, derived from trifluo-
roethanol, for the synthesis of substituted analogues.
Interestingly, the corresponding fluorovinylstannane ether
obtained by reacting the 1-lithio-1-fluorovinyl enol ether
with tributyltin chloride provided only moderate yields
of coupling products with aryl iodides. However, it was
felt that 2-substituted-1-fluorovinylstannanes would be
an efficient synthetically equivalent 1-fluoroalkene anion
for the synthesis of di- and trisubstituted fluoroolefins
rovinylstannanes has provided an entry to monosubsti-
tuted 2-fluoro-1-olefins. The palladium-catalyzed cross-
coupling of 2-trimethylsilyl-1-fluorovinylstannane (1b)
4
with aryl iodides or acid chlorides under Stille coupling
5
conditions has been demonstrated to be useful for the
design and synthesis of mechanism-based enzyme inhibi-
tors containing 2-fluorinated terminal olefins. A similar
coupling reaction of an unsubstituted 1-fluorovinylstan-
nane (1a ) with an acid chloride, aryl iodide, or aryl
triflate was subsequently developed to avoid the removal
6
based on the successful synthesis of terminal 1-fluoro-
4,6,7
2
-substituted olefins.
Such fluorovinylstannanes would
3
b,3c
be an alternative for labile 1-fluoro-1-lithioalkenes.
(
1) (a) Welch, J . T. Tetrahedron 1987, 43, 3123. b) Man, J . Chem.
Herein, we report the scope of the stereospecific pal-
ladium-catalyzed cross-coupling reactions of 2-monosub-
stituted- and 2,2-disubstituted-1-fluorovinylstannnanes
with aryl iodides and acid chlorides to form multisubsti-
tuted monofluoroolefins. A portion of this work was
published as a communication.10
Soc. Rev. 1987, 16, 381. c) Welch, J . T.; Eswarakrishman, S. Fluorine
in Bioorganic Chemistry; Wiley: New York, 1991.
(
Application; Filler, R., Kobayashi, Y., Yagupolskii, L. M., Eds.;
Elsevier: Amsterdam, 1993. (b) Banks, R. E., Smart, B. E., Tatlow, J .
C., Eds.; Organofluorine Chemistry: Principle and Commercial Ap-
plications; Plenum Press: New York, 1994. (c) Resnati, G.; Soloshnok,
V. A. Fluoroorganic Chemistry: Synthetic Challenges and Biomedical
Rewards; Tetrahedron Symposia in-Print No. 58; Tetrahedron 1996,
2) (a) Organofluorine Compounds in Medicinal and Biomedical
Resu lts a n d Discu ssion
5
2, 1. (d) Hibi, S.; Kikuchi, K.; Yoshimura, H.; Nagai, M.; Tai, K.; Hida,
T. J . Med. Chem. 1998, 41, 3245.
3) (a) McCarthy, J . R.; Huber, E. W.; Le, T.-B.; Laskovics, F. M.;
(
The condensations of carbonyl compounds with the in
situ generated Horner-Wittig reagent formed between
fluoromethyl phenyl sulfone11 and diethyl chlorophos-
phate in the presence of lithium hexamethyldisilazane
Matthews, D. P. Tetrahedron 1996, 52, 45 and references therein. (b)
Kuroboshi, M.; Yamada, N.; Takebe, Y.; Hiyama, T. Tetrahedron Lett.
995, 36, 6271. (c) Pelter, A.; Kvicala, J . Tetrahedron Lett. 1997, 38,
877. (d) Hossain, M. A. Tetrahedron Lett. 1997, 38, 49. (e) Shimizu,
M.; Hata, T.; Hiyama, T. Tetrahedron Lett. 1997, 38, 4591. (f) Eddarir,
S.; Francesch, C.; Mestdagh, H. Rolando, C. Bull. Soc. Chim. Fr. 1997,
1
4
1
34, 741. (g) Benayoud, F.; Chen, L. Moniz, G. A.; Zapata, A. J .;
Hammond, G. B. Tetrahedron 1998, 54, 15541.
4) Matthews, D. P.; Gross, R. S.; McCarthy, J . R.Tetrahedron Lett.
994, 35, 1027.
5) (a) Stille, J . K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (b)
Stille, J . K.; Groh, B. L. J . Am. Chem. Soc. 1987, 109, 813.
6) (a) McCarthy, J . R.; Matthews, D. P.; Stemerick, D. M.; Huber,
(7) Matthews, D. P.; Waid, P. P.; Sabol, J . S.; McCarthy, J . R.
Tetrahedron Lett. 1994, 35, 5177.
(8) Shi, G-q.; Cao, Z-y.; Zhang, X-b. J . Org. Chem. 1995, 60, 6608.
(9) Percy, J . M,; Wilkes, R. D. Tetrahedron 1997, 53, 14749.
(10) Chen, C.; Wilcoxen, K.; Kim, K.-I.; McCarthy, J . R. Tetrahedron
Lett. 1997, 38, 7677. Also see: Lu, L.; Burton, D. J . Tetrahedron Lett.
1997, 38, 7673.
(
1
(
(
E. W.; Bey, P.; Lippert, B. J .; Snyder, R. D.; Sunkara, P. J . Am. Chem.
Soc. 1991, 113, 7439. (b) Moore, W. R.; Schatzman, G. L.; J arvi, E. T.;
Gross, R. S.; McCarthy, J . R. J . Am. Chem. Soc. 1992, 114, 360.
(11) (a) McCarthy, J . R.; Matthews, D. P.; Paolini, J . P. Org. Synth.
1993, 72, 209. (b) Matthews, D. P.; Persichepti, R.; McCarthy, J . R.
Org. Prep. Proced. Int. 1994, 605.
1
0.1021/jo982200n CCC: $18.00 © 1999 American Chemical Society
Published on Web 04/15/1999

Mild and Stereospecific Method to Monofluoroolefins
J . Org. Chem., Vol. 64, No. 10, 1999 3477
Sch em e 1
Sch em e 2
Sch em e 3
proceeded readily to give 1-fluorovinyl sulfones 2a -f.12,18a
The E- and Z-isomers were easily separated on a silica
gel column. Reaction of the 1-fluorovinyl sulfones with 2
1
3
equiv of tributyltin hydride in refluxing benzene af-
forded the required 1-fluorovinylstannanes 3-8 in good
to excellent yields (Scheme 1).3 This transformation is
stereoselective when the 1-fluorovinyl sulfone is 2,2-
disubstituted. The two stereoisomers of 2-monosubsti-
tuted-1-fluorovinylstannanes were separable by silica gel
chromatography. The E configuration of the fluorovinyl-
a
along with the reduced product, 1-methyl-2-fluorostyrene
3
stannanes 3-5 were established on the basis of the J H-F
(18) (Scheme 2). The modest yields and sluggish nature
1
4
coupling constant (about 60 Hz). The stereochemistry
of the coupling are consistent with results reported by
1
19
of 6 was determined by H-{ F} NOE NMR experiments,
9
Percy for the condensation of monofluorovinylstannane
which were reported earlier for compound 7.3
a
enol ethers with aryl iodides.
The palladium-catalyzed coupling reaction of orga-
It has been reported that copper(I) iodide cocatalyst
accelerates sluggish or otherwise unsuccessful Stille
coupling reactions.16 When 1-fluorovinylstannane E-6
was coupled with 4′-iodoacetophenone (9b) in refluxing
THF under nitrogen for 30 min, using 5 mol % of Pd-
5
,15
nostannanes with organic halides and sulfonates,
known as Stille coupling, has already been established
as an efficient stereospecific method for the formation of
carbon-carbon bonds under mild conditions. In an effort
to arrive at the optimum conditions for the coupling of
(
PPh
coupling product Z-14b was isolated in 83% yield (entry
5). The effect of CuI cocatalyst was demonstrated by the
3 4
) and 1 equiv of CuI as the cocatalyst, the desired
3
-8, a variety of reaction conditions (catalyst, solvent,
and temperature) were tried using (E)-1-fluoro-2-phen-
ylpropenyltributylstannane (E-6) and iodobenzene (9a )
or 4′-iodoacetophenone (9b) (Table 1). Initial attempts at
coupling 1-fluorovinylstannane E-6 with iodobenzene
1
following coupling results. CuI alone as the catalyst did
not yield Z-14b from E-6 and 4′-iodoacetophenone (9b)
(
entry 16), and Pd(PPh
coupling product in refluxing THF (entry 13). The Pd-
0)/CuI-cocatalyzed coupling reaction also proceeded at
ambient temperature with a longer reaction time (entry
3 4
) alone only gave 10% of the
3 4
under standard Stille conditions [Pd(PPh ) (5 mol %),
THF, reflux] only gave the expected cross-coupling
product, (Z)-1,2-diphenyl-1-fluoropropene (Z-14a ), in 10%
yield after 18 h, while most of the starting material
remained unchanged (entry 13). The lower reactivity of
(
1
1
7). The results obtained from the coupling reaction of
-fluorovinylstannanes 3-8 with a variety of halides
1
-fluorovinylstannane E-6, compared with the corre-
(Scheme 3) are summarized in Table 1. The cross-
sponding nonfluorinated vinylstannanes, apparently is
due to the electronic effects of fluorine. Also, E-6 is less
reactive than the unsubstituted 1-fluorovinylstannane
coupling reaction of (E)-1-fluoro-2-phenylvinyltributyl-
stannane (3) with a variety of aryl iodides (entries 1-6)
proceeded smoothly to give the substituted fluoroolefins
(
1a ), as would be expected on the basis of steric effects.7
1
1a -f as single geometric isomers in good to excellent
The coupling reaction of E-6 with iodobenzene proceeded
in 42% isolated yield when carried out in DMF at 120 °C
for 18 h to give Z-14a (entry 14). 1,4-Dimethyl-1,4-
diphenyl-2,3-difluorobutadiene (17a ) was also isolated as
the result of homocoupling of the starting tin compound,
yields. With electron-rich aryl iodides, the reaction was
slower and yields were slightly lower (see entries 4 and
6
4
). It should be noted that coupling reactions with
-iodoanisole (entries 4 and 18) yielded homocoupling
product 17b or 17a in addition to the desired product.
More homocoupling was observed when both an electron
rich aromatic iodide and sterically hindered vinylstan-
nane were used (entry 18). In addition to aryl iodides,
compound 3 was coupled with (E)-1-iodo-1-hexene (9g)
(
12) McCarthy, J . R.; Matthews, D. P.; Edwards, M. L.; Stemerick,
D. M.; J arvi, E. T. Tetrahedron Lett. 1990, 31, 5449.
13) Watanabe, Y.; Ueno, Y.; Araki, T.; Endo, T.; Okawara, M.
Tetrahedron Lett., 1986, 27, 215.
14) Emsley, J . W.; Phillips, L.; Wray, V. Fluorine Coupling Con-
stants; Pergamon: New York, 1977.
15) Echavarren, A. M.; Stille, J . K. J . Am. Chem. Soc. 1988, 110,
557. (b) Stille, J . K.; Tanaka, M. J . Am. Chem. Soc. 1987, 109, 3785.
(
(
(
(16) Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind,
L. S. J . Org. Chem. 1994, 59, 5905 and references therein.
1

3
478 J . Org. Chem., Vol. 64, No. 10, 1999
Chen et al.

Mild and Stereospecific Method to Monofluoroolefins
J . Org. Chem., Vol. 64, No. 10, 1999 3479
Sch em e 4
Sch em e 5
1
19
F igu r e 1. Summary of proton NOE and H-{ F} NOE NMR
experiments. Normal NOE:f Fluorine NOE:F.
to afford the diene 11g in 83% yield (entry 7) with
retention of double bond geometry present for both
coupling partners, and with benzoyl chloride to afford
ketone 11h in 92% yield (entry 8). Attempts to couple 3
with ethyl chloroformate gave only the dimerized product
1
7b in 89% yield (entry 9). (E)-1-Fluoro-2-cyclohexylvi-
nyltributylstannane (5) demonstrated similar reactivity
as 3 and coupled with 4′-iodoacetophenone (9b) to afford
compound 13 in 72% yield (entry 12). In all cases, only a
single isomer was isolated from the coupling reaction.
The Z stereochemistry of products 11-13 was readily
assigned on the basis of the J H,F coupling constant
between 39 and 46 Hz and by comparison with model
compounds.14
Sch em e 6
The palladium/copper(I) iodide cocatalyzed coupling
reaction of 2,2-disubstituted-1-fluorovinylstannanes 6-8
with a variety of aryl iodides 9 in THF at room temper-
ature or reflux gave the corresponding fluoroolefins as
single geometric isomers in good yields (entries 15, 18,
2
2, and 25). Thus, coupling of E-6 with 4′-iodoacetophe-
was observed on the vinyl methyl group (δ 2.20 ppm) and
the ortho-protons of acetylphenyl group (δ 7.22 ppm) but
not the unsubstituted phenyl group.
none (9b) gave Z-14b in 83% yield (entry 15). Similarly,
reaction of Z-6 with 9b gave the corresponding E-14b in
7
proceeded much faster than that of Z-6, which is consis-
tent with increased steric hindrance for Z-6. Without
copper(I) iodide, the coupling reactions required higher
temperatures (DMF/120 °C) and gave lower yields (en-
tries 14 and 24). The assignments for the geometric
isomers of 14 and 15 were not straightforward. On the
5% yield (entry 22), although the reaction of E-6
The palladium-catalyzed cross-coupling reactions of
1
1
-fluorovinylstannanes E-6 and Z-6 with acid chlorides
0a and 10b were carried out under the same condi-
1
7
tions to afford R-fluoro-R,â-unsaturated ketones 14 in
good yields (entries 19, 20, and 23) (Scheme 4). Attempts
to couple E-6 with ethyl oxalyl chloride or ethyl chloro-
formate provided only the homocoupling product 1,4-
dimethyl-1,4-diphenyl-2,3-difluorobutadiene (17a) (Scheme
5
basis of the uniformity of the Stille coupling mechanism
and the well-established stereochemistry3a for the 1-fluo-
5
).
Coupling of 1-fluorovinylstannane 3 with iodobenzene
9a ) under a carbon monoxide atmosphere gave the direct
coupling product 11a and CO insertion product 11h in
rovinylstannanes, the E and Z configurations initially
were assumed for compounds 14 and 15. Proton NMR
experiments show a NOE between the vinyl methyl group
and the ortho-proton on the acetylphenyl group of Z-14b
but not E-14b (Figure 1). Thus, for Z-14b when the vinyl
methyl (δ 2.19 ppm) was irradiated, NOEs were observed
for ortho-protons on both phenyl rings (at 7.50 and 7.66
ppm, respectively). However, for E-14b, only one NOE
was observed for ortho-protons (at 7.27 ppm) on the
unsubstituted phenyl ring. The results of proton NOE
NMR experiments are summarized in Figure 1. We
(
3
1
6% and 53% yield, respectively (Scheme 6). Although
-fluorovinyltributylstannanes 1a and 1c also are re-
7
,8
ported to couple with 4-acetylphenyl triflate, reaction
of 3 with phenyl triflate failed under similar conditions
(with or without CuI) even in the presence of 2 equiv of
LiCl, and the only isolated product was (E,E)-1,4-diphen-
yl-2,3-difluorobutadiene (17b).
Chromones are present in a variety of biologically
active molecules. 3-Formylchromones are readily avail-
able and useful intermediates for various derivatives.
Condensation of 6,8-dichloro-3-formylchromone with flu-
1
19
applied the H-{ F} NOE NMR technique to confirm the
retention of configuration for the conversion of tin
compounds E-6 and Z-63a to Z-14b and E-14b. Thus, by
irradiation of the fluorine (at -104.8 ppm) on Z-14b, a
strong NOE was observed on the ortho-protons of both
phenyl groups (at 7.50 and 7.66 ppm) but not the vinyl
methyl group (δ 2.19 ppm). Alternatively, by irradiation
of the fluorine (at -107.4 ppm) on E-14b, a strong NOE
(
17) For the palladium-catalyzed coupling reaction of organotins
with acid chlorides, see: (a) Milstein, D.; Stille, J . K. J . Org. Chem.
979, 44, 1614. (b) Labadie, J .; Tueting, D.; Stille, J . K. J . Org. Chem.
1983, 48, 4634.
1

3
480 J . Org. Chem., Vol. 64, No. 10, 1999
Chen et al.
Sch em e 7
1-F lu or ovin yl Su lfon e 2a -d . The following 1-fluorovinyl
sulfones were synthesized from fluoromethylphenyl sulfone
and aldehydes or ketones as reported.1
2,18
(
E)-1-F lu or o-1-p h en ylsu lfon yl-2-p h en ylet h en e (2a ).
1
2,18
1
White solid (lit. mp 77.5-78.5 °C
), 80% yield. H NMR:
7
.05 (d, J H,F ) 30 Hz, 1H), 7.38 (m, 3H), 7.58 (m, 5H), 8.01 (d,
2
J ) 7.8 Hz, 2H). Anal. Calcd for C14H11FO S (262.3): C, 64.11;
H, 4.23. Found: C, 63.85; H, 4.50.
(
E)-6,8-Dich lor o-3-(2-flu or o-2-p h en ylsu lfon ylvin yl)-4-
1
ch r om on e (2b). Yellow solid, mp 212-214 °C, 49% yield. H
NMR: 7.50 (d, J ) 36 Hz, 1H), 7.62 (t, J ) 7.8 Hz, 2H), 7.73
(
t, J ) 7.8 Hz, 1H), 7.76 (d, J ) 2.4 Hz, 1H), 8.03 (d, J ) 7.8
19
Hz, 2H), 8.12 (d, J ) 2.4 Hz, 1H), 8.55 (s, 1H). F NMR: -117.9
d, J ) 36.7 Hz). CIMS: m/e 399 (M + H). Anal. Calcd for
Cl FO S (399.22): C, 51.15; H, 2.27. Found: C, 50.91;
H, 2.34.
E)-1-Flu or o-1-p h en ylsu lfon yl-2-cycloh exyleth en e (2c).
(
C
17
H
9
2
4
(
1
Colorless oil, 76% yield. H NMR: 1.10-1.70 (m, 10 H), 2.42
(
(
(
m, 1H), 6.11 (dd, J ) 9.7 Hz, 33.5 Hz, 1H), 7.53 (m, 2H), 7.62
19
m, 1H), 7.90 (m, 2H). F NMR: -128.3 (d, J ) 33.4 Hz). MS
+
2
EI): m/e 268 (M ). Anal. Calcd for C14H17FO S (268.35): C,
6
2.66; H, 6.39. Found: C, 62.60; H, 6.52.
E)-1-F lu or o-1-p h en ylsu lfon yl-2-p h en ylp r op en e (E-
(
1
1
1
2
3
)
d ). Brownish oil, 1.2 g (68% yield); H NMR: 2.52 (d, J )
.6 Hz, 3H), 7.33 (m, 5H), 7.59 (t, J ) 7.8 Hz, 2H), 7.69 (t, J
1
9
7.8 Hz, 1H), 8.01 (d, J ) 7.8 Hz, 2H). F NMR: -119.9 (s).
+
HRMS (FAB): calcd. for C15
2
H
14FO
2
S [M + H] 277.0699; found
77.0689.
Z)-1-F lu or o-1-p h en ylsu lfon yl-2-p h en ylp r op en e (Z-2d ).
(
oromethyl phenyl sulfone under the reaction conditions
described above afforded the vinyl sulfone 2b, which was
converted to the corresponding fluorovinylstannane 4.
Palladium(0)/copper iodide catalyzed cross-coupling reac-
tion of 4 with ethyl 3-iodoacrylate (9h ) gave the diene
derivative 12a in 68% isolated yield (Scheme 7). Simi-
larly, coupling of 4 with benzoyl chloride afforded the
ketone derivative 12b in 48% yield. It should be noted
that these highly functionalized chromones are poten-
tially useful intermediates for the synthesis of biologically
active fluorinated molecules.
1
1
White solid, mp 57-59 °C (from ether-hexanes), 0.16 g (9%
1
yield); H NMR: 2.10 (d, J ) 4.5 Hz, 3H), 7.18-8.00 (m, 10H).
1
9
F NMR: -119.8 (s). MS (EI): m/e 276 (M+). Anal. Calcd for
15 2
C H13FO S (276.33): C, 65.20; H, 4.74. Found: C, 64.89; H,
4
.86.
1-F lu or ovin ylsta n n a n es 3-6. The following 1-fluorovi-
nylstannanes were synthesized from 1-fluorovinyl sulfones and
tributyltin hydride as reported.3
a,18
(
E)-1-F lu or o-1-tr ibu tylsta n yl-2-p h en yleth en e (3). Col-
1
orless oil, 74% yield. H NMR: 0.95-1.85 (m, 27H), 5.77 (d,
H,F ) 57.3 Hz, 0.84H), 5.77 (dd, J H,F ) 57.3 Hz, J H,Sn ) 15.6
Hz, 0.16H); 7.29 (t, J ) 7.5 Hz, 1H), 7.41 (t, J ) 7.5 Hz, 2H),
.64 (d, J ) 7.5 Hz, 2H). 19F NMR: -91.4 (d, J F,H ) 57.3 Hz,
0.84F), -91.4 (dd, J F,H ) 57.3 Hz, J F,Sn ) 238.6 Hz, 0.16F).
J
7
Con clu sion
1
3
C NMR: 11.5 (d, J C,F ) 2.0 Hz), 15.1, 28.6 (s), 28.6 (d, J C,Sn
57.0 Hz), 30.3 (s), 30.3 (d, J C,Sn ) 21.4 Hz), 124.4 (d, J C,F
6.9 Hz), 124.4 (dd, J ) 6.9 Hz, J C,Sn ) 67.5 Hz), 128.3, 129.8,
A palladium/copper-cocatalyzed cross-coupling reaction
of 1-fluorovinylstannanes (3-8) with a variety of aryl
iodides has been developed that affords substituted
monofluoroolefins 11-16 with the same double bond
geometry present in the coupling partners. The reaction
takes place with CuI present as a cocatalyst at ambient
temperature or in refluxing tetrahydrofuran. Many func-
tional groups are tolerated on the substrates. Highly
functionalized and stereoisomerically pure monofluoro-
olefins were obtained under mild conditions by the cross-
coupling of the appropriate organic halides with the
)
)
C,F
130.2 (d, J C,F ) 7.5 Hz), 135.2 (d, J C,F ) 5.3 Hz), 135.2 (dd,
J
C,F ) 5.3 Hz, J C,Sn ) 31.5 Hz), 175.8 (d, J C,F ) 330 Hz). MS
+
(
(
EI): m/e 353 and 355 (M - Bu). Anal. Calcd for C20
H
33FSn
411.18): C, 58.42; H, 8.09; F, 4.62. Found: C, 58.15; H, 8.45;
F, 4.40.
E)-6,8-Dich lor o-3-(2-flu or o-2-t r ib u t ylst a n ylvin yl)-4-
(
1
ch r om on e (4). Colorless oil, 55% yield. H NMR: 0.85-1.65
2
(
m, 27H), 6.07 (d, J ) 60 Hz, 0.84H), 6.07 (dd, J H,F ) 60 Hz,
3
J
Sn,H ) 14.7 Hz, 0.16H), 7.70 (d, J ) 2.6 Hz, 1H), 8.11 (d, J )
19
2.6 Hz, 1H), 8.75 (d, J ) 3.0 Hz, 1H). F NMR: -84.4 (d, J )
6.4 Hz, 0.84F), -84.4 (dd, 2
.16F). MS (EI): calcd for C23
J
H
F,Sn ) 210.7,
31Cl
3
J
F,H ) 56.4 Hz,
FO Sn: 546; found: m/e
5
0
4
1
-fluorovinylstannanes. When the coupling reaction was
2 2
carried out under a carbon monoxide atmosphere or with
an acid chloride as the substrate, R-fluoro-R,â-unsatur-
ated ketones were obtained stereospecifically in good
yield. This mild, selective, and general method will be
useful for the synthesis of a wide variety of new mono-
fluoroolefins.
+
89, 491 (M - Bu).
(
E)-1-F lu or o-1-tr ibu tylsta n yl-2-cycloh exyleth en e (5).
1
Colorless oil, 80% yield. H NMR: 0.85-1.75 (m, 37H), 2.65
(
m, 1H), 4.70 (dd, J H,H ) 8.5 Hz, J H,F ) 56.4, 0.84H), 4.70 (ddd,
19
J H,H ) 8.5 Hz, J H,Sn ) 10.0 Hz, J
H,F
) 56.4 Hz, 0.16H).
F
NMR: -103.3 (d, J F,H ) 54.9 Hz, 0.84F), -103.3 (dd, J F,H
)
5
(
J
4.9 Hz, J F,Sn ) 274.5 Hz, 0.16F). 13C NMR: 11.2, 15.0, 27.5
s), 27.5 (d, J C,Sn ) 37.3 Hz, 16%), 28.5, 28.8, 30.2 (s), 30.2 (d,
C,Sn ) 20.0 Hz, 16%), 32.0 (s), 32.0 (d, J C,Sn ) 10.0 Hz, 16%),
34.8, 132.0 (s), 132.0 (d, J C,Sn ) 61.5 Hz, 16%), 169.4 (d, J C,F
Exp er im en ta l Section
Gen er a l. (E)-1-Fluoro-1-phenylsulfonyl-2-(phenethyl)pro-
pene (2e), (E)-1-fluoro-1-tributylstanyl-2-(phenethyl)propene
)
+
314.8 Hz). MS (EI): m/e 359 and 361 (M - Bu). Anal. Calcd
for C20 39FSn (417.23): C, 57.57; H, 9.42; F, 4.55. Found: C,
57.14; H, 9.78; F, 4.32.
E)-1-F lu or o-1-tr ibu tylsta n yl-2-p h en ylp r op en e (E-6).
(
7), and 1-fluoro-1-tributylstanyl-2,2-diphenylethene (8) were
H
3
,12,18
synthesized by literature procedures.
(
1
Colorless oil, 65% yield. H NMR: 0.91 (t, J ) 7 Hz, 9H), 1.10
dt, J ) 7.0, 7.0 Hz, 6H), 1.35 (m, 6H), 1.66 (m, 6H), 1.92 (d,
J ) 4.2 Hz, 3H), 7.21 (t, J ) 7.5 Hz, 1H), 7.31 (t, J ) 7.5 Hz,
(
18) McCarthy, J . R.; Matthew, D. P.; Paolini, J . P. Org. Synth. 1995,
2, 216. (b) Koizumi, T.; Hagi, T.; Horie, Y.; Takeuchi, Y. Chem Pharm.
Bull. 1987, 35, 3959. (c) Appell, R. A. Synth. Commun. 1995, 25, 3583.
(
7

Mild and Stereospecific Method to Monofluoroolefins
J . Org. Chem., Vol. 64, No. 10, 1999 3481
1
9
19
2
H), 7.38 (d, J ) 7.5 Hz, 2H). F NMR: -110.2 (s, 0.84F),
(m, 1H), 7.40 (m, 5H), 7.62 (m, 4H). F NMR: -113.3 (d, J )
2
13
13
-
2
1
100.2 (d, J F,Sn ) 271.3 Hz, 0.16F). C NMR: 11.9 (d, J C,F
)
)
40 Hz). C NMR: 105.7 (d, J C,F ) 10.6 Hz), 124.1 (d, J C,F )
.6 Hz), 15.1 (s), 19.8 (d, J C,F ) 11.2 Hz, 84%), 19.8 (dd, J C,F
7.5 Hz), 127.1 (d, J C,F ) 2.6 Hz), 128.4, 128.5, 128.7, 132.7 (d,
1.2 Hz, J C,Sn ) 22.0 Hz, 16%), 28.6 (s), 28.6 (d, J C,Sn ) 58.1
J
C,F ) 27.8 Hz), 133.5 (d, J C,F ) 3.2 Hz), 157.0 (d, J C,F ) 257.9
+
Hz, 16%), 30.4 (s), 30.4 (d, J C,Sn ) 21.8 Hz, 16%), 128.2, 129.4,
Hz). MS (EI) m/e 198 (M ). Anal. Calcd for C14
H
11F (198.24):
1
29.5, 130.7, 139.2 (d, J C,F ) 7.7 Hz), 168.6 (d, J C,F ) 312.0
C, 84.82; H, 5.59. Found: C, 84.68; H, 5.54.
+
Hz). MS (EI): m/e 367 and 369 (M - Bu), 310 and 312, 251
and 253; Anal. Calcd. for C21 35FSn (425.21): C, 59.32; H, 8.30;
F, 4.47. Found: C, 58.94; H, 8.71; F, 4.19.
Z)-1-F lu or o-1-tr ibu tylsta n yl-2-p h en ylp r op en e (Z-6).
(Z)-1-F lu or o-1-(4-a cetylp h en yl)-2-p h en yleth en e (11b).
From Method B, 0.5 h; white solid, mp 139-141 °C (from
H
1
ether-hexanes), 90% yield. H NMR: 2.63 (s, 3H), 6.46 (d, J
(
) 39.3 Hz, 1H), 7.18 (t, J ) 7.4 Hz, 1H), 7.40 (t, J ) 7.4 Hz,
2H), 7.67 (d, J ) 7.4 Hz, 2H), 7.74 (d, J ) 8.4 Hz, 2H), 8.00 (d,
1
Colorless oil, 10% yield. H NMR: 0.74 (m, 6H), 0.89 (m, 9H),
1
9
13
1
2
)
.25 (m, 6H), 1.39 (m, 6H), 2.10 (d, J ) 5.2 Hz, 3H), 7.22 (m,
J ) 8.4 Hz, 2H). F NMR: -114.3 (d, J ) 39.2 Hz). C NMR:
H), 7.32 (m, 3H). 19F NMR: -96.7 (s, 0.84F), -96.7 (d, J F,Sn
26.7, 108.2 (d, J
C,F
) 10.0 Hz), 124.1 (d, J ) 7.7 Hz), 127.8 (d,
1
3
3
259.4 Hz, 0.16F). C NMR: 11.9, 15.0, 16.1 (d, J C,F ) 14.1
J C,F ) 2.6 Hz), 128.5, 128.6, 129.0, 129.2, 132.9 (d, J
) 3.2
C,F
3
3
Hz), 16.1 (dd, J C,F ) 14.1 Hz, J C,Sn ) 17.9 Hz, 16%), 28.5 (s),
Hz) 136.7 (d, J C,F ) 3.7 Hz), 155.1 (d, J
) 244.0 Hz), 197.1.
C,F
2
3
+
2
8.5 (d, J C,Sn ) 61.2 Hz, 16%), 30.1 (s) 30.1 (d, J C,Sn ) 20.3
16 13
MS (EI): m/e 240 (M ). Anal. Calcd for C H FO (240.28): C%
2
Hz, 16%), 128.6, 129.6, 129.9, 135.2 (d, J C,F ) 4.2 Hz), 142.0
79.98; H, 5.45. Found: C, 79.78; H, 5.67.
3
1
(
d, J C,F ) 14.8 Hz), 169.7 (d, J C,F ) 312.6 Hz). HRMS (FAB):
(
Z)-1-(4-Ch lor op h en yl)-1-fu or o-2-p h en yleth en e (11c).
+
calcd. for C21H35FSn (M - Bu) 367.1041; found 367.1024.
From Method B, 1 h; white solid, mp 114-116 °C (from ether-
Cr oss-Cou p lin g Rea ction of 1-F lu or ovin ylsta n n a n es
1
hexanes), 91% yeild; H NMR: 6.35 (d, J ) 39.6 Hz, 1H), 7.27
(
3-8) w ith Or ga n ic Ha lid es: Typ ica l P r oced u r e. Meth od
A. Under argon in a three-neck 10 mL flask, iodobenzene (204
mg, 1 mmol) was added to a stirred DMF (3 mL) solution of
(
7
m, 1H), 7.36 (d, J ) 8.1 Hz, 2H), 7.37 (t, J ) 7.4 Hz, 2H),
19
.56 (d, J ) 7.4 Hz, 2H), 7.62 (d, J ) 8.1 Hz, 2H). F NMR:
13
-
1
115.1 (d, J ) 39.8 Hz). C NMR: 106.2 (d, J ) 10.3 Hz),
25.4 (d, J ) 7.5 Hz), 127.4 (d, J ) 2.3 Hz), 128.5 (s), 128.7 (d,
J ) 2.3 Hz), 128.9 (d, J ) 8.0 Hz), 131.2 (d, J ) 28.6 Hz),
Pd(PPh
mmol), and (E)-1-fluoro-1-tributylstanyl-2-phenylpropene (E-
, 453 mg, 1 mmol) at room temperature. After 18 h of stirring
3 4
) (400 mg, 0.35 mmol), anhydrous LiCl (42 mg, 1
6
1
(
33.2 (d, J ) 3.2 Hz), 134.7 (s), 156.0 (d, J ) 257.7 Hz). MS
EI): m/e 232 (M ). Anal. Calcd for C14H10ClF (232.68): C,
2.27; H, 4.33. Found: C, 72.04; H, 4.54.
Z)-1-(4-Meth oxyp h en yl)-1-fu or o-2-ph en yleth en e (11d).
at 120 °C, the reaction was quenched with water, and the
product was extracted into ether. The organic layer was dried
4
and concentrated in vacuo. Chromatography on
silica gel (hexanes) afforded (Z)-1-fluoro-1,2-diphenylpropene
Z-14a ) as a colorless oil (90 mg, 42%).
Meth od B. A mixture of (E)-1-fluoro-1-tributylstanyl-2-
phenylpropene (E-6, 215 mg, 0.5 mmol), 4′-iodoacetophenone
130 mg, 0.5 mmol), tetrakis(triphenylphosphine)palladium-
0) (30 mg, 0.026 mmol), and CuI (90 mg, 0.47 mmol) in THF
8 mL) was heated at reflux for 30 min. The black deposit
indicated the completion of the reaction. The mixture was
concentrated in vacuo and chromatographed on silica gel with
:5 ethyl acetate-hexanes to give (Z)-1-fluoro-1-(4-acetylphen-
yl)-2-phenylpropene (Z-14b) as a white solid (105 mg, 83%
yield).
Meth od C. Under argon in a three-neck 10 mL flask,
benzoyl chloride (140 mg, 1 mmol) was added to a stirred THF
3 mL) solution of Pd(PPh ) (400 mg, 0.35 mmol) and (E)-1-
3 4
fluoro-1-tributylstanyl-2-phenylpropene (E-6, 425 mg, 1 mmol)
at room temperature. After 5 h of stirring at 65 °C, the reaction
was quenched with water, and the product was extracted into
+
7
over MgSO
(
From Method B, 3 h; white solid, mp 88-89 °C (from ether-
(
1
hexanes), 71% yeild; H NMR: 3.80 (s, 3H), 6.11 (d, J ) 39.3
Hz, 1H), 6.90 (d, J ) 8.7 Hz, 2H), 7.22 (t, J ) 7.4 Hz, 1H),
7
.35 (dd, J ) 7.4, 7.8 Hz, 2H), 7.55 (d, J ) 8.7 Hz, 2H), 7.61
(
(
(
1
9
1
3
(
d, J ) 7.8 Hz, 2H). F NMR: -114.0 (d, J ) 39.5 Hz).
NMR: 55.3 (s), 104.0 (d, J ) 10.9 Hz, 125.3 (d, J ) 28.1 Hz),
25.7 (d, J ) 7.6 Hz), 126.8 (d, J ) 2.1 Hz), 128.4 (s), 128.5
s), 128.6 (s), 133.8 (d, J ) 3.2 Hz), 157.1 (d, J ) 257.6 Hz),
C
1
(
1
+
60.1 (s). MS (EI): m/e 228 (M ). Anal. Calcd for C15
228.26): C, 78.93; H, 4.74. Found: C, 78.87; H, 4.87.
Z)-5-(1-Flu or o-2-ph en ylvin yl)-1,4-dim eth ylu r acil (11e).
From Method B, 2 h; white solid (from ether-hexanes), mp
H13FO
1
(
(
1
1
2 2
75-177 °C (from CH Cl -ether-hexanes), 89% yield. H
NMR: 3.39 (s, 3H), 3.42 (s, 3H), 7.17 (d, J ) 46.0 Hz, 1H),
(
7
7
.24 (t, J ) 7.5 Hz, 1H), 7.34 (t, J ) 3.5 Hz, 2H), 7.53 (s, 1H),
19
.56 (d, J ) 7.5 Hz, 2H). F NMR: -115.9 (d, J ) 46.0 Hz).
13
2
C NMR: 29.6, 38.9, 110.2 (d, J ) 5.3 Hz), 128.7, 129.8, 130.6
3
1
3
(
1
d, J ) 7.6 Hz), 135.1 (d, J ) 250.9 Hz), 151.9, 161.2 (d, J )
ether. The organic layer was dried (MgSO
in vacuo. Chromatography on silica gel (methylene dichloride-
hexanes, 1:1) afforded (Z)-2-fluoro-1,4-diphenylbut-2-en-1-one
Z-14d ) as a colorless oil (120 mg, 50% yield).
Meth od D. A mixture of (E)-1-fluoro-1-tributylstanyl-2-
4
) and concentrated
+
0.5 Hz). MS (ion spray): m/e 261 (M + H). Anal. Calcd for
(260.27): C, 64.61; H, 5.03; N, 10.76. Found: C,
4.66; H, 5.41; N, 10.51.
Z)-4-(1-Flu or o-2-ph en ylvin yl)pyr r ole (11f). From Method
B, 4 h; tan solid (from CH Cl
14 2 2
C H13FN O
6
(
(
2
2
-hexanes), mp >200 °C (from
phenylpropene (E-6, 215 mg, 0.5 mmol), hydrocinnamoyl
chloride (100 mg, 0.6 mmol), tetrakis(triphenylphosphine)-
palladium(0) (60 mg, 0.05 mmol), and CuI (95 mg, 0.5 mmol)
in THF (8 mL) was heated to reflux for 20 min. Chromatog-
raphy on silica gel with 1:5 ethyl acetate-hexanes gave (Z)-
1
ether-hexanes); 67% yield. H NMR: 3.90 (brs, 1H), 6.03 (d,
J ) 40.1 Hz, 1H), 7.26 (t, J ) 7.4 Hz, 1H), 7.38 (dd, J ) 7.4,
1
9
7
.6 Hz, 2H), 7.59 (d, J ) 7.6 Hz, 2H), 7.90 (brs, 2H). F NMR:
+
-
115.9 (d, J ) 40 Hz). MS (ion spray): m/e 189 (M + H).
Anal. Calcd for C11 FN (188.21): C, 70.20; H, 4.82; N, 14.88.
Found: C, 69.97; H, 5.06; N, 14.46.
-Flu or o-1-ph en yl-octa-(1Z,3E)-dien e (11g). From Method
H
9
2
1
,5-diphenyl-4-fluoro-5-methyl-4-buten-3-one (Z-14e) as a col-
orless oil (110 mg, 82% yield).
2
Meth od E. A mixture of (E)-1-fluoro-1-tributylstanyl-2-
phenylethene (3, 205 mg, 0.5 mmol), iodobenzene (120 mg, 0.59
mmol), tetrakis(triphenylphosphine)palladium(0) (60 mg, 0.05
mmol), and CuI (95 mg, 0.5 mmol) in THF (8 mL) was heated
to reflux under a carbon monoxide atmosphere (CO balloon)
for 1 h. Chromatography on silica gel with 1:5 ethyl acetate-
hexanes gave (Z)-1,3-diphenyl-2-fluoro-2-propen-1-one (11h )
as a colorless oil (61 mg, 53% yield). A byproduct, compound
1
B, 2 h; colorless oil, 83% yield. H NMR: 0.92 (t, J ) 7.2 Hz,
3
5
H), 1.36 (m, 4H), 2.16 (m, 2H), 5.53 (d, J ) 39.4 Hz, 1H),
.90 (ddt, J ) 1.2, 15.9, 25.8 Hz, 1H), 6.12 (dt, J ) 7.2, 15.9
1
9
Hz, 1H), 7.19 (m, 1H), 7.31 (m, 2H), 7.52 (m, 2H). F NMR:
-
1
117.2 (dd, J ) 27.4, 39.5 Hz). 13C NMR: 9.7, 18.0, 26.9, 28.0,
03.4 (d, J C,F ) 9.5 Hz), 118.2, J C,F ) 22.9 Hz), 122.5 (d, J C,F
2.6 Hz), 124.1, 124.2, 124.3, 128.7 (d, J C,F ) 3.7 Hz), 152.5
)
(
+
d, J C,F ) 256.5 Hz). MS (EI): m/e 204 (M ). Anal. Calcd for
1
1a , was also isolated as 36 mg of a white solid (36%).
Z)-1-F lu or o-1,2-d ip h en yleth en e (11a ). From Method B,
h; white solid, mp 93-94 °C (from hexanes) (lit. mp 93.5-
14
C H
H, 8.56; F, 9.04.
17F (204.28): C, 82.31; H, 8.39; F, 9.30. Found: C, 81.89;
(
1
9
2
0
1
(Z)-1,3-Dip h en yl-2-flu or o-2-p r op en -1-on e (11h ). From
Method C; colorless oil, (lit. bp 119-120 °C/0.01 Torr ), 92%
4 °C ), 86% yield. H NMR: 6.31 (d, J ) 39.6 Hz, 1H), 7.26
2
1
(
19) This complicated coupling was analyzed based on AA′XX′ four
nuclei spin system, see: Gruther, H., Ed.; NMR Spectroscocy; J ohn
(20) Barton, D. H. R.; Hesse, R. H.; J ackman, G. P.; Ogunkoya, L.;
Wiley & Son: Georg Thieme Verlag, 1992.
Pechet, M. M. J . Chem. Soc., Perkin Trans. 1 1974, 739.

3
482 J . Org. Chem., Vol. 64, No. 10, 1999
Chen et al.
1
yield. H NMR: 6.83 (d, J ) 36.6 Hz, 1H), 7.40 (m, 2H), 7.46
79.32; H, 6.24. Found: C, 79.00; H, 6.34. 2,3-Diflu or o-1,4-
d ip h en ylh exa -2,4-d ien e (17a , 26 mg, 37% yield) was also
isolated.
(
t, J ) 7.5 Hz, 2H), 7.57 (t, J ) 7.5 Hz, 1H), 7.67 (dd, J ) 7.5,
1
9
1
)
1
.8 Hz, 2H), 7.85 (d, J ) 8.7 Hz, 2H). F NMR: -118.4 (d, J
1
3
36.6 Hz). C NMR: 121.6 (d, J ) 5.8 Hz), 129.8, 130.2,
(Z)-2-F lu or o-1,4-d ip h en ylbu t-2-en -1-on e (Z-14d ). From
1
30.6, 130.7, 131.4 (d, J ) 2.6 Hz), 131.9, 132.0, 134.3, 155.7
d, J ) 271.3 Hz), 189.3 (d, J ) 28.2 Hz). HRMS (FAB): calcd.
for C15 11FO 226.0794; found 226.0781.
,8-Dich lor o-3-[2-flu or o-2-(4-et h oxyca r b on yl-(1Z,3E)-
bu ta d ien -yl)]-4-ch r om on e (12a ). From Method B, room
temperature,16 h; white solid, mp 196-198 °C (from CH Cl
ether-hexanes), 68% yield. H NMR: 1.34 (t, J ) 7.5 Hz, 3H),
.26 (q, J ) 7.5 Hz, 2H), 6.27 (d, J ) 15.6 Hz, 1H), 6.43 (d, J
Method C; colorless oil, 120 mg, 50% yield. H NMR: 2.34 (d,
(
J ) 3.7 Hz, 3H), 7.35-7.60 (m, 8H), 7.90 (d, J ) 6.5 Hz, 2H).
1
9
+
H
F NMR: -116.0 (s). GC-MS: 240 (M ). HRMS (EI): calcd.
+
6
for C16
H
13FO [M + H] 241.1029, found 241.1024.
(Z)-1,5-Dip h en yl-4-flu or o-5-m eth yl-4-bu ten -3-on e (Z-
1
-
14e). From Method D; colorless oil, 110 mg, 82% yield. H
2
2
1
NMR: 2.44 (d, J ) 3.6 Hz, 3H), 3.02 (m, 4H), 7.20-7.40 (m,
10H). 19F NMR: -114.9. MS (EI): m/e 267 (M ). Anal. Calcd
+
4
)
39.3 Hz, 1H), 7.18 (dd, J ) 15.6, 27.0 Hz, 1H), 7.75 (d, J )
for C18
6.24.
H17FO (268.33): C, 80.57; H, 6.39. Found: C, 80.31; H,
2
.4 Hz, 1H), 8.13 (d, J ) 2.4 Hz, 1H), 8.72 (d, J ) 2.4 Hz, 1H).
1
9
F NMR: -112.3 (dd, J ) 27.4, 39.5 Hz). MS (EI): m/e 356
(E)-1,5-Dip h en yl-4-flu or o-5-m eth yl-4-bu ten -3-on e (E-
+
1
(
M ). Anal. Calcd for C16
H
11Cl
2
FO
4
(357.16): C, 53.81; H, 3.10;
14e). From Method D, 1 h; colorless oil, 78% yield. H NMR:
Cl, 19.85; F, 5.32. Found: C, 53.54; H, 3.43; Cl, 19.67; F, 4.99.
Z)-6,8-Dich lor o-3-(2-flu or o-2-ben zoylvin yl)-4-ch r om -
on e (12b). From Method C, room temperature, 6 h; colorless
2.15 (d, J ) 4.5 Hz, 3H), 2.84 (m, 4H), 7.10-7.34 (m, 10H).
1
9
+
F NMR: -121.2. HRMS: Calcd. for C18H17FO [M + H]
(
2
68.1263, found 268.1268.
1
(1E)-1-F lu or o-2-m eth yl-1, 4-d ip h en ylbu ten e (15). From
oil, 48% yield. H NMR: 7.21 (d, J ) 39.0 Hz, 1H), 7.52 (t, J
1
Method A; colorless oil, R
f
) 0.25 (hexanes), 45% yield. H
)
7.6 Hz, 2H), 7.64 (t, J ) 7.6 Hz, 1H), 7.77 (d, J ) 2.8 Hz,
NMR: 1.89 (d, J ) 3.3 Hz, 3H), 2.38 (t, J ) 7.0 Hz, 2H), 2.78
1
H), 7.86 (d, J ) 7.6 Hz, 2H), 8.18 (d, J ) 2.8 Hz, 1H), 8.83 (d,
1
9
19
(t, J ) 7.0 Hz, 2H), 7.08-7.35 (m, 10H). F NMR: -102.5.
J ) 2.7 Hz, 1H). F NMR: -112.7 (d, J ) 38.9 Hz). GC-MS:
+
+
HRMS (FAB): Calcd. for C17
H17F M 240.1314, found 240.1319.
m/e 257 (M - PhCO). Anal. Calcd for C18
C, 59.53; H, 2.50. Found: C, 59.26; H, 2.72. (Z)-6,8-Dich lor o-
-(2-flu or ovin yl)-4-ch r om on e was also isolated as a byprod-
9 2 3
H Cl FO (363.17):
1
-F lu or o-1-(4-a cet ylp h en yl)-2,2-d ip h en ylet h en e (16).
1
From Method B, 6 h; colorless oil, 87% yield. H NMR: 2.54
3
1
(s, 3H), 7.14 (m, 2H), 7.23-7.37 (m, 10H), 7.75 (d, J ) 8.1 Hz,
uct. H NMR: 6.10 (dd, J ) 46.5, 5.1 Hz, 1H), 6.82 (dd, J )
+
2
H). 19F NMR: -105.7; HRMS (FAB): calcd. for C22
H17FO M
8
1
8
4.0, 5.1 Hz, 1H), 7.73 (d, J ) 2.5 Hz, 1H), 8.12 (d, J ) 2.5 Hz,
19
316.1263, found 316.1251.
,4-Dim eth yl-1,4-d ip h en yl-2,3-d iflu or obu ta d ien e (17a )
a n d (E)-1-Meth yl-2-flu or ostyr en e (18). Dim er iza tion of
E)-1-F lu or o-1-tr ibu tylsta n yl-2-p h en ylp r op en e. A mixture
H), 8.60 (d, J ) 1.8 Hz, 1H). F NMR: -116.1 (dd, J ) 46.5,
2.9 Hz). MS (EI): calcd. for C11 Cl FO m/e 258, found 258
1
H
5
2
2
+
(M ).
(
(
Z)-1-Flu or o-1-(4-acetylph en yl)-2-cycloh exyleth en e (13).
1
of the tin compound E-6 (300 mg, 0.7 mmol), ethyl oxalyl
chloride (136 mg, 1.0 mmol), tetrakis(triphenylphosphine)-
palladium(0) (80 mg, 0.065 mmol), and CuI (190 mg, 1.0 mmol)
in THF (10 mL) was stirred at rt for 3 h. Chromatography on
silica gel with 1:10 ethyl acetate-hexanes gave the reduced
product 18 and the dimeric compound 17a . Data for 18:
colorless oil (82 mg, 28%).2 H NMR: 1.93 (d, J ) 4.8 Hz, 3H),
From Method B, 4 h; colorless oil, 72% yield. H NMR: 1.10-
1
3
2
.85 (m, 10H), 2.59 (s, 3H), 2.65 (m, 1H), 5.43 (dd, J ) 9.3,
7.8 Hz, 1H), 7.56 (d, J ) 8.1 Hz, 2H), 7.91 (d, J ) 8.1 Hz,
1
9
H). F NMR: -102.7 (d, J ) 37.4 Hz). HRMS (FAB): calcd.
+
for C16
H19FO M 246.1420, found 246.1403.
(
Z)-1-F lu or o-1,2-d ip h en ylp r op en e (Z-14a ). From Method
3 1
2
2
1
A, colorless oil (lit. mp 78.6-79.6 °C ), 90 mg (42% yield); H
6
.67 (d, J ) 84.5 Hz, 1H), 7.29 (t, J ) 7.2 Hz, 1H), 7.38 (t, J
1
9
NMR: 2.14 (d, J ) 3.0 Hz, 3H), 7.28-7.56 (m, 10H). F NMR:
1
9
)
7.2 Hz, 2H), 7.51 (d, J ) 7.2 Hz, 2H). F NMR: -128.8 (d,
+
-
102.7 (s). GC-MS (EI): m/e 212 (M ). HRMS (FAB): calcd.
2
J
9 9
F,H ) 84.3 Hz). MS (EI): calcd. for C H F m/e 136, found
+
for C15
Z)-1-F lu or o-1-(4-a cetylp h en yl)-2-p h en ylp r op en e (Z-
4b). From Method B; white solid (105 mg, 83% yield).
H13F M 212.1001, found 212.1006.
+
1
1
2
7
36 (M ). Data for 17a : colorless oil (160 mg, 54%). H NMR:
.14 (t, J ) 3.6 Hz, 3H), 7.35 (t, J ) 7.0 Hz, 2H), 7.43 (t, J )
(
1
19
.0 Hz, 4H), 7.52 (d, J ) 4H). F NMR: -113.0 (s). MS (EI):
Analytical sample was obtained by recrystallization from
+
calcd. for C18
H
16
F
2
m/e 270, found 270 (M ).
1
ether-hexanes, mp 96-8 °C; H NMR: 2.19 (d, J ) 3.0 Hz,
1
,4-Dip h en yl-2,3-d iflu or o-bu ta d ien e (17b). Dim er iza -
3
2
H), 2.65 (s, 3H), 7.32 (t, J ) 7.4 Hz, 1H), 7.41 (t, J ) 7.4 Hz,
H), 7.50 (d, J ) 7.4 Hz, 2H), 7.66 (d, J ) 8.4 Hz, 2H), 8.02 (d,
tion of (E)-1-F lu or o-1-tr ibu tylsta n yl-2-p h en yleth en e. A
mixture of the tin compound 3 (215 mg, 0.5 mmol), ethyl
chloroformate (126 mg, 1.0 mmol), tetrakis(triphenylphos-
phine)palladium(0) (45 mg, 0.04 mmol), and CuI (95 mg, 0.5
mmol) in THF (8 mL) was stirred at rt overnight. Chroma-
tography on silica gel with 1:5 ethyl acetate-hexanes gave the
dimeric product 1,4-diphenyl-2,3-difluoro-butadiene (17b) as
a white solid (60 mg, 89% yield), which solidified on standing,
1
9
13
J ) 8.4 Hz, 2H). F NMR: -104.8; C NMR: 20.0 (d, J ) 3.0
Hz), 28.0, 118.5 (d, J ) 15.0 Hz), 128.8, 129.5, 129.6, 129.9,
1
2
30.0, 138.2, 138.9 (d, J ) 29.0 Hz), 139.6, 152.9 (d, J C,F )
+
43.5 Hz), 198.8. MS (EI): m/e 254 (M ). Anal. Calcd for
15FO (254.31): C, 80.29; H, 5.95. Found: C, 80.12; H, 6.04.
E)-1-F lu or o-1-(4-a cetylp h en yl)-2-p h en ylp r op en e (E-
17
C H
(
1
1
4b). From Method B, 12 h; colorless oil, 75% yield:
H
1
3
4
mp 102-4 °C; H NMR: 6.28 (six peaks, J H,F ) 39.1 Hz, J H,F
4
NMR: 2.20 (d, J H,F ) 4.0 Hz, 3H), 2.53 (s, 3H), 7.15-7.30 (m,
3
5
19
)
4.0 Hz, J F,F ) 36.4 Hz, J H,H ) 0 Hz, 2H), 7.73 (t, J ) 7.1
1
9
13
7
1
1
1
H), 7.73 (d, J ) 8.4 Hz, 2H). F NMR: -107.4; C NMR:
Hz, 2H), 7.81 (dd, J ) 7.1, 7.9 Hz, 4H), 8.03 (d, J ) 7.9 Hz,
3
9.4 (d, J C,F ) 7.5 Hz), 27.9, 121.2, 128.9, 129.1, 129.3, 129.4,
19
3
4
4
H). F NMR: -127.0 (six peaks, J H,F ) 39.1 Hz, J H,F ) 4.0
3 5
2
30.1, 137.5, 138.6 (d, J C,F ) 29.2 Hz), 140.5 (d, J ) 6.0 Hz,
Hz, J H,H ) 36.4 Hz, J H,H ) 0 Hz, 2H). MS (EI): calcd. for
1
53.7 (d,
J
C,F ) 232.5 Hz), 198.7. HRMS (FAB): calcd. for
+
C
16
H
12
F
2
m/e 242, found 242 (M ).
+
C
17
H
15FO [M + H] 254.1107, found 254.1126.
Z)-1-Flu or o-1-(4-m eth oxyph en yl)-2-ph en ylpr op en e (Z-
Ack n ow led gm en t. We gratefully acknowledge Dr.
(
1
1
19
1
2
7
4c). From Method B, 5 h; colorless oil, 50% yield. H NMR:
.14 (d, J ) 3.0 Hz, 3H), 3.87 (s, 3H), 6.98 (d, J ) 8.6 Hz, 2H),
Edward Huber for performing the H-{ F} NOE NMR
experiments.
.28 (t, J ) 7.4 Hz, 1H), 7.40 (t, J ) 7.4 Hz, 2H), 7.49 (m, 4H).
Su p p or tin g In for m a tion Ava ila ble: Copies of the 1H-
F} NOE NMR spectra of E-14b and Z-14b. This material
+
MS (EI): m/e 242 (M ). Anal. Calcd for C16
H
15FO (242.30): C,
{19
is available free of charge via the Internet at http://pubs.acs.org.
(
21) Elkik, E.; Imbeaux-Oudotte, M. Tetrahedron Lett. 1985, 26,
977.
22) Bornstein, J .; Borden, M. R.; Nunes, F.; Tarlin, H. I. J . Am.
Chem. Soc. 1963, 85, 1609.
3
J O982200N
(
(23) Burton, D. J .; Greenlimb, P. E. J . Org. Chem. 1975, 40, 2796.