Synthesis and reactions of α-fluorovinylphosphonium salts

Article abstract of DOI:10.1039/a905878h

The α-fluorovinyltriphenylphosphonium Inflate 4 is prepared in high yields by the diphenylphosphinylation of 1,1-difluoroethylene 1 and subsequent quaternization of the phosphine 2 with diphenyliodonium triflate in the presence of CuCl. The salt 4 then undergoes Michael addition followed by Wittig olefination to give the corresponding monofluoroethylene compounds in good yields. The reaction of 4 with the caesium salts of salicylaldehyde derivatives in DMF at 130 °C affords the corresponding monofluorinated chromenes in a one-pot synthesis. The hydrolysis of 4 in the presence of sodium hydroxide gives triphenylphosphine oxide in quantitative yield. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/a905878h

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Synthesis and reactions of ꢀ-fluorovinylphosphonium salts
Takeshi Hanamoto,* Keiko Shindo, Miki Matsuoka, Yasuhide Kiguchi and Michio Kondo
Department of Chemistry, Saga University, Honjyo-machi, Saga 840-8502, Japan
Received (in Cambridge, UK) 20th July 1999, Accepted 15th November 1999
1
The α-fluorovinyltriphenylphosphonium triflate 4 is prepared in high yields by the diphenylphosphinylation
of 1,1-difluoroethylene 1 and subsequent quaternization of the phosphine 2 with diphenyliodonium triflate
in the presence of CuCl. The salt 4 then undergoes Michael addition followed by Wittig olefination to give the
corresponding monofluoroethylene compounds in good yields. The reaction of 4 with the caesium salts of
salicylaldehyde derivatives in DMF at 130 ЊC affords the corresponding monofluorinated chromenes in a one-pot
synthesis. The hydrolysis of 4 in the presence of sodium hydroxide gives triphenylphosphine oxide in quantitative yield.
Introduction
Much effort has been made to introduce fluorine into organic
compounds due to its dramatic effects on their structure, stabil-
ity, reactivity and biological activity.1 Among them, the prepar-
ation of monofluorinated compounds can be divided into two
main methods: one is the direct exchange of hydrogen by fluor-
ine,2 and the other is the use of monofluorinated building
blocks. As the former requires special techniques and equip-
ment, the latter has recently received much attention and has
become a significant procedure in this field.3 Vinylphos-
phonium salts are useful building blocks for the construction
of two-carbon-extended olefinic compounds.4 Although some
substituted vinylphosphonium salts have been synthesized
and their reactivities examined,5 the syntheses of fluorine-
substituted vinylphosphonium salts have been rarely reported.6
We have considered the α-fluorovinyltriphenylphosphonium
triflate 4 as a promising candidate for the monofluorinated
building block which would be stable and easy to handle. We
have reported our preliminary findings7 and now provide a full
account of the work.
Scheme 1
as a by-product. We next carefully investigated the reaction
conditions and found that when the reaction was conducted
over the temperature range of Ϫ60 to Ϫ40 ЊC in THF–toluene
Results and discussion
under
a 1,1-difluoroethylene atmosphere, the yield was
Previously used methods for the preparation of the vinyl-
triphenylphosphonium salts generally include elimination reac-
tions of the corresponding alkyltriphenylphosphonium salts.
Recently, Stang and co-workers have introduced a new method
using the palladium-catalyzed vinylation of triphenylphosphine
with vinyl triflates.8 However, these convenient methods
appeared to be not applicable to the salt 4, which required the
development of a new method from us. Our synthetic route
for the preparation of the α-fluorovinylphosphonium salts is
depicted in Scheme 1. We initially attempted to examine the
convenient preparation of α-fluorovinyldiphenylphosphine 2 as
the precursor for the salt. Since it is well documented that
nucleophilic addition followed by elimination of the fluoride for
producing 1,1-difluoroethylene derivatives is easy,9 it was there-
fore anticipated that the reaction of lithium diphenylphos-
phide10 and 1,1-difluoroethylene 1 should afford a convenient
preparation of 2. Thus, to a THF solution of lithium diphenyl-
phosphide prepared from lithium and chlorodiphenylphos-
phine was bubbled 1,1-difluoroethylene at Ϫ78 ЊC and the
resulting mixture was stirred for 16 h at the same temperature.
After the usual work-up, we obtained 2 in modest yield. In
order to improve the yield of 2, we conducted the reaction
at elevated reaction temperatures (Ϫ78–0 ЊC); however, the
undesirable 1,1-bis(diphenylphosphinyl)ethylene was produced
improved up to 86%. The added co-solvent, toluene, facilitated
stirring of the reaction mixture at these low temperatures. The
obtained 2 was generally oxidized in air to give the correspond-
ing phosphine oxide.
Quaternization of 2 with iodomethane smoothly proceeded
to give the α-fluorovinyl(methyl)diphenylphosphonium iodide 3
in 91% yield. However, the alkyldiphenylphosphonium salts
exhibited less performance compared with the corresponding
triphenylphosphonium salts;11 therefore, we examined the
quaternization of 2 with aryl compounds.12 The reaction of 2
with aryl halides or aryl triflates did not take place under
certain conditions. Kitamura et al. have described the direct
S-arylation of benzo[b]thiophenes to produce the 1-arylbenzo-
[b]thiophenium salt.13 This prompted us to use the diaryl-
iodonium salts for the P-arylation of 2 instead of the S-arylation
of the sulfides. We attempted to use the method of Kitamura.13
Compound 2 was treated with diphenyliodonium triflate in the
presence of a catalytic amount of Cu(OAc)2 at 140 ЊC for 30 min
under an Ar atmosphere. The reaction mixture turned into
a brown-black oil. It was difficult to solidify the residual oil
after the addition of an excess of diethyl ether to the oil. How-
ever, based on the NMR spectra, we confirmed the formation
of 4. After many attempts, we optimized the best reaction con-
ditions. Thus, the α-fluorovinyltriphenylphosphonium triflate
J. Chem. Soc., Perkin Trans. 1, 2000, 103–107
This journal is © The Royal Society of Chemistry 2000
103

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Table 1 Reaction of α-fluorovinylphosphonium salts with various
aldehydes
Entry
RONa
RЈCHO
Yield (%)a
E/Zb
1c
2
MeONa
EtONa
PhCHO
43
63
52
75
80
70
69
77
52/48
40/60
53/47
43/57
35/65
47/53
52/48
41/59
37/63
3c
4
5
6
7
8
9
10
4-MeOC6H4CHO
4-PhC6H4CHO
4-NCC6H4CHO
2-Naphthaldehyde
Cinnamaldehyde
Hydrocinnamaldehyde
82
trace
Scheme 3
a Isolated yield. b Determined by capillary GC-MS analysis. c Salt 3 was
used.
4 was obtained by the reaction of diphenyliodonium triflate
in the presence of CuCl in 1,1,2,2-tetrachloroethane at
140 ЊC in 82% yield. We believe that this P-arylation method
provides a new route for the synthesis of aryl phosphonium
salts.
For comparison of the reactivities of the vinylphosphonium
bromide (Schweizer’s reagent), the reaction of 4 with sodium
ethoxide and benzaldehyde was carried out (Scheme 2). The
Chart 1 Monofluorinated chromene derivatives. All reactions were
conducted in DMF for 40 h at 130 ЊC.
2).17 Contrary to our expectation, the reaction of the sodium
salt of salicylaldehyde 7 with 4 in acetonitrile at 70 ЊC afforded
no cyclized product (run 1), presumably due to the influence
of the fluorine atom at the α-position of the salt. A further
attempt to obtain the desired cyclized product in the above
reaction was made by examining the effect of the solvent. How-
ever, the lack of satisfactory yield caused us to abandon the use
of the sodium salt of the salicylaldehyde. Next, we focused on
the effects of varying the cation on the salicylaldehyde and
investigated three different bases. Unfortunately, the use of the
potassium, magnesium, and lithium salts of the salicylalde-
hyde resulted in low yields or no reaction (runs 6, 7, and 8,
respectively).
We next turned our attention to the potential of the CsF–
Si(OEt)4 system.18 Although we examined the above reaction
conditions for the cyclization of the salicylaldehyde, no
improved yields were obtained. We also investigated the scope
and limitations of the in situ preparation and reaction of the
caesium salts of other salicylaldehyde derivatives. The cycliz-
ation of 3-methoxysalicylaldehyde and 2-hydroxy-1-naphthal-
dehyde proceeded to give the corresponding monofluorinated
chromene derivatives 9, 10 in 47 and 31% yield, respectively
(Chart 1). On the other hand, the cyclization of 5-nitrosalicyl-
aldehyde resulted in a low yield (14%) of the product 11. It is
noteworthy that the CsF–Si(OEt)4 system was effective for the
above cyclization, because we confirmed that no cyclization of
the sodium salts of 2-hydroxy-1-naphthaldehyde and 5-nitro-
salicylaldehyde occurred under the conditions employed for the
salicylaldehyde (entry 5 in Table 2). The reaction of the caesium
salt of o-hydroxyacetophenone with the α-fluorovinyltriphenyl-
phosphonium triflate did not give the anticipated product.
Furthermore, we examined the hydrogenation of the
obtained monofluorinated chromenes to produce the corre-
sponding monofluorinated chromanes.19 We employed three
types of catalysts for the hydrogenation of 8.20 All the reactions
were conducted under hydrogen at atmospheric pressure and
room temperature. These results are shown in Scheme 4. The
Rh/Al2O3 catalyst was the most effective for the transformation
without any loss of the fluorine atom in the molecule. Thus,
3-fluorochromane 12 was obtained in 73% yield. In the case
of 9, PtO2-catalyzed hydrogenation gave the corresponding
Scheme 2
β-ethoxy-α-fluoroethyltriphenylphosphonium ylide, generated
via the addition of an ethoxide anion to 4 in ethanol at room
temperature, reacted with benzaldehyde to provide 3-ethoxy-
2-fluoro-1-phenylpropene 5a as a 43:57 mixture of E and Z
isomers in 75% yield (Table 1, entry 4). The E/Z ratio was
determined by capillary GC-MS analysis. The geometrical iso-
mers were separated from each other on a silica gel column and
characterized based on their NMR spectra. The coupling con-
stants with fluorine showed a value of 20 Hz for the E isomer
and 39 Hz for the Z isomer. As expected, the reactivity of 4
was much higher than that of 3 as compared with the yields
(entries 1 vs. 2 and 3 vs. 4). Although aromatic aldehydes and
an α,β-unsaturated aldehyde gave good results, the aliphatic
aldehyde gave poor results. A similar reaction using sodium
piperidide as the nucleophile instead of sodium ethoxide
in THF at 50 ЊC gave the corresponding 2-fluoro-1-phenyl-3-
piperidinopropene 6 as a mixture of diastereomers in 44%
total yield (Scheme 3). Furthermore, no reaction occurred with
ketones (cyclohexanone and acetophenone) due to possible
steric hindrance in the Wittig reaction.
These results prompted us to utilize 4 for the synthesis of
a variety of monofluorinated heterocyclic ring systems, since
the synthesis of fluorinated heterocyclic compounds has also
become an important area of agrochemical and pharmaceutical
studies due to their unique biological properties.14 Among
them, the syntheses of fluorinated chromenes are quite
limited,15 although the chromene nucleus is also encountered in
insecticides and natural products.16
We initially examined the synthesis of 3-fluoro-2H-chromene
8 as a model compound based on Schweizer’s protocol (Table
104
J. Chem. Soc., Perkin Trans. 1, 2000, 103–107

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Table 2 Cyclization of salicylaldehyde under various conditions
Run
M
Base (mol. equiv.)
Solventa
T/ЊC
t/h
Yield(%)
1
2
3
4
5
6
7
8
9
Na
Na
Na
Na
Na
H
H
H
H
H
None
None
None
None
Acetonitrile
tert-BuOH
DMSO
DMF
DEM–DMF 4:1
THF
DEM–DMF 4:1
DEM–DMF 4:1
DEM–DMF 4:1
DMF
70
80
120
130
80
50
80
80
80
130
88
40
16
40
40
16
16
16
40
40
0
27
32
20
35
0
0
7
8
34
None
TMSOK (1.0)
EtMgBr (1.0)
BuLi (1.0)
CsF (1.7)/Si(OEt)4 (1.3)
CsF (1.7)/Si(OEt)4 (1.3)
10
a DEM: Diethoxymethane.
produce triphenylphosphine oxide 14. On the other hand, the
oxidation of 2 conducted in acetone containing hydrogen per-
oxide gave the corresponding α-fluorovinyldiphenylphosphine
oxide 15 in 84% yield.
In conclusion, the α-fluorovinyltriphenylphosphonium tri-
flate 4 can be a useful reagent for the synthesis of compounds
containing monofluorinated olefinic moieties in one pot. Such
systems are not readily available using general methods.
Experimental
Mps were measured with a Yanagimoto micro melting point
apparatus MP-S3 and are uncorrected. IR spectra were
1
recorded on a Perkin-Elmer Spectrum 2000. H NMR spectra
were measured on a JEOL JNM-GX270. Chemical shifts are
given by δ relative to that of internal Me4Si (TMS). Mass spec-
tra were obtained with a Shimadzu GCMS QP-5000. Fast-
atom-bombardment mass spectra (FABMS) were obtained
with a JEOL JMS-HX110A. Elemental analyses were per-
formed on a Yanagimoto MT3 CHN corder or were accom-
plished at the service center of the elementary analysis of
organic compounds, Kyushu University. Analytical TLC was
performed on silica gel plates (Merck, Kieselgel 60 F254,
20 × 20 cm, 0.25 mm). All solvents were purified before use:
THF and diethoxymethane (DEM) were dried over sodium
benzophenone ketyl radical; 1,1,2,2-tetrachloroethane, DMF,
DMSO, MeCN and EtOH were distilled from calcium hydride.
The procedures for the preparation of 2, 4 and 5 have already
been reported.7
Scheme 4
8-methoxychromane 13 with loss of the fluorine atom in the
molecule in 63% yield.
Finally, other reactivities of 4 were examined (Scheme 5).
ꢀ-Fluorovinyl(methyl)diphenylphosphonium iodide 3
A mixture of α-fluorovinyldiphenylphosphine 2 (1.50 g, 6.52
mmol) and iodomethane (1.2 mL, 19.3 mmol) in toluene (2.0
mL) was stirred at room temperature in the dark for 16 h. After
the addition of diethyl ether (≈25 mL) to the mixture, the result-
ing precipitates were collected by filtration. Recrystallization
from hexane–CH2Cl2 gave the desired product (2.20 g, 91%),
mp 126.4–128.3 ЊC; ν(KBr)/cmϪ1 3103, 3062, 3007, 2959, 2884,
2801, 1636, 1588, 1482, 1435, 1407, 1370, 1322, 1298, 1274,
1186, 1162, 1114, 1070, 1036, 992, 900, 859, 791, 750, 685 and
644; δH(CDCl3) 3.27 (3H, d, J 13.7 Hz), 5.79 (1H, ddd, J 6.4,
7.3, 49.3 Hz), 6.49 (1H, ddd, J 6.4, 21.5, 29.8 Hz), 7.7–8.0 (m,
10 H); FABMS: m/z 245 (Mϩ Ϫ I) (Calc. for C15H15FIP: C,
48.41; H, 4.06. Found: C, 48.19; H, 3.91%).
Scheme 5
The hydrolysis of the salt was carried out in aq. alcohols or
aq. THF containing excess of sodium hydroxide.21 Neither
reaction produced the corresponding β-ethoxy-α-fluoroethyl-
diphenylphosphine oxide or the corresponding α-fluoro-
vinyldiphenylphosphine oxide, but they did quantitatively
(E)- and (Z)-2-Fluoro-3-methoxy-1-phenylpropene 5b
Total yield 63%. (E)-isomer: ν(neat)/cmϪ1 3055, 3027, 2986,
J. Chem. Soc., Perkin Trans. 1, 2000, 103–107
105

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2925, 2815, 1680, 1598, 1492, 1400, 1288, 1257, 1217, 1189,
1142, 1097, 954, 917, 750, 699 and 631; δH(CDCl3) 3.42 (3H, s),
4.14 (2H, d, J 23.0 Hz), 6.48 (1H, d, J 19.5 Hz), 7.24–7.38 (5H,
m); MS m/z 166 (50%, Mϩ), 151 (42), 135 (41), 133 (62), 115
(82), 109 (100) (Calc. for C10H11FO: C, 72.27; H, 6.67. Found:
C, 72.10; H, 6.71%).
184 (31), 183 (95), 170 (38), 165 (100), 159 (86), 153 (93) (Calc.
for C15H15FO: C, 78.24; H, 6.57. Found: C, 78.31; H, 6.68%).
(Z)-isomer: mp 39.0–41.0 ЊC; ν(KBr)/cmϪ1 3068, 3034, 2977,
2863, 1699, 1676, 1605, 1564, 1489, 1445, 1404, 1377, 1349,
1288, 1261, 1213, 1162, 1099, 1008, 866, 832, 764, 729 and 697;
δH(CDCl3) 1.29 (3H, t, J 6.8 Hz), 3.64 (2H, q, J 6.8 Hz), 4.18
(2H, d, J 15.1 Hz), 5.93 (1H, d, J 38.6 Hz), 7.40–7.95 (7H, m);
m/z 230 (98, Mϩ), 201 (34), 186 (30), 185 (72), 183 (81), 170 (37),
166 (30), 165 (100), 159 (87), 153 (78) (Found: C, 78.14; H,
6.63%).
(Z)-isomer: ν(neat)/cmϪ1 3055, 3027, 2986, 2993, 2822, 1693,
1600, 1530, 1495, 1451, 1383, 1349, 1220, 1189, 1165, 1155,
1101, 1091, 958, 917, 879, 753 and 694; δH(CDCl3) 3.44 (3H, s),
4.08 (2H, d, J 15.6 Hz), 5.76 (1H, d, J 38.6 Hz), 7.25–7.55 (5H,
m); m/z 166 (75%, Mϩ), 151 (47), 135 (59), 133 (69), 115 (95),
109 (100) (Found: C, 72.56; H, 6.75%).
(E)- and (Z)-(E)-5-Ethoxy-4-fluoro-1-phenylpenta-1,3-diene 5g
Total yield 82%. These compounds could not be separated.
ν(neat)/cmϪ1 3021, 2977, 2870, 1673, 1492, 1448, 1346, 1138,
1097, 968, 886, 750 and 692; δH(CDCl3) 1.25 (3H, t, J 6.8 Hz),
1.26 (3H, t, J 6.8 Hz), 3.57 (2H, q, J 6.8 Hz), 3.59 (2H, q, J 6.8
Hz), 4.07 (2H, d, J 15.6 Hz), 4.29 (2H, d, J 20.5 Hz), 5.69 (1H,
dd, J 10.7, 34.2 Hz), 6.13 (1H, dd, J 11.2, 18.1 Hz), 6.55 (2H, d,
J 16.1 Hz), 6.80 (1H, ddd, J 1.0, 11.2, 16.1 Hz), 7.09 (1H, dd,
J 10.7, 16.1 Hz), 7.20–7.45 (10H, m); (E)-isomer: m/z 206 (36%,
Mϩ), 159 (35), 147 (49), 146 (75), 142 (38), 141 (40), 129 (100),
128 (55), 115 (77), 91 (53); (Z)-isomer: m/z 206 (41%, Mϩ), 159
(33), 147 (34), 146 (63), 142 (34), 141 (42), 129 (100), 128 (50),
115 (70), 91 (41) [Calc. for C13H15FO (M): 206.1096. Found:
Mϩ, 206.1109].
(E)- and (Z)-3-Ethoxy-2-fluoro-1-(4Ј-methoxyphenyl)propene 5c
Total yield 80%. (E)-isomer: ν(neat)/cmϪ1 2978, 2932, 2897,
2870, 1683, 1609, 1574, 1515, 1464, 1383, 1295, 1252, 1180,
1142, 1096, 1035, 886, 862, 831, 770 and 715; δH(CDCl3) 1.25
(3H, t, J 6.8 Hz), 3.58 (2H, q, J 6.8 Hz), 3.81 (3H, s), 4.17 (2H,
d, J 23.4 Hz), 6.40 (1H, d, J 20.5 Hz), 6.88 (2H, d, J 8.8 Hz),
7.20 (2H, d, J 8.8 Hz); m/z 210 (51%, Mϩ), 166 (31), 165 (100),
139 (68), 133 (35), 121 (32), 115 (37), 91 (30) (Calc. for
C12H15FO2: C, 68.55; H, 7.19. Found: C, 68.73; H, 7.37%).
(Z)-isomer: ν(neat)/cmϪ1 2978, 2932, 2897, 2836, 1693, 1609,
1574, 1515, 1506, 1346, 1295, 1252, 1179, 1162, 1097, 1036, 879,
859, 821 and 770; δH(CDCl3) 1.26 (3H, t, J 6.8 Hz), 3.59 (2H, q,
J 6.8 Hz), 3.81 (3H, s), 4.11 (2H, d, J 16.1 Hz), 5.70 (1H, d,
J 38.6 Hz), 6.87 (2H, d, J 8.8 Hz), 7.46 (2H, d, J 8.8 Hz); m/z
210 (52%, Mϩ), 166 (32), 165 (100), 139 (60), 133 (31), 115 (33),
91 (29) (Found: C, 68.65; H, 7.40%).
(E)- and (Z)-2-Fluoro-1-phenyl-3-piperidinopropene 6
Total yield 44%. (E)-isomer: ν(neat)/cmϪ1 2936, 2853, 2777,
1676, 1453, 1302, 1282, 1223, 1133, 1098, 1065, 1039, 997, 882,
860, 787, 750 and 700; δH(CDCl3) 1.35–1.50 (2H, m), 1.55–1.70
(4H, m), 2.35–2.55 (4H, m), 3.28 (2H, d, J 22.5 Hz), 6.40 (1H, d,
J 21.5 Hz), 7.22–7.36 (5H, m); m/z 219 (82%, Mϩ), 218 (48), 136
(52), 135 (100), 133 (72), 128 (30), 116 (30), 115 (58), 109 (36),
98 (85), 97 (36), 84 (94), 83 (61) [Calc. for C14H19FN (M ϩ H):
220.1501. Found: m/z, 220.1469].
(E)- and (Z)-1-(4Ј-Biphenylyl)-3-ethoxy-2-fluoropropene 5d
Total yield 70%. (E)-isomer: ν(neat)/cmϪ1 3055, 3027, 2978,
2856, 1683, 1600, 1486, 1445, 1380, 1274, 1257, 1217, 1145,
1096, 1005, 886, 764 and 695; δH(CDCl3) 1.27 (3H, t, J 6.8 Hz),
3.60 (2H, q, J 6.8 Hz), 4.23 (2H, d, J 23.4 Hz), 6.48 (1H, d,
J 20.0 Hz), 7.33–7.62 (9H, m); m/z 256 (68%, Mϩ), 196 (43), 191
(53), 185 (100), 179 (38), 178 (56) (Calc. for C17H17FO: C, 79.66;
H, 6.68. Found: C, 79.40; H, 6.80%).
(Z)-isomer: ν(neat)/cmϪ1 2936, 2855, 2809, 2770, 1689, 1496,
1451, 1398, 1372, 1345, 1301, 1275, 1251, 1111, 1040, 996, 885,
862, 785, 754 and 694; δH(CDCl3) 1.35–1.50 (2H, m), 1.55–1.70
(4H, m), 2.40–2.60 (4H, m), 3.18 (2H, d, J 18.1 Hz), 5.65 (1H,
d, J 38.6 Hz), 7.15–7.55 (5H, m); m/z 219 (100%, Mϩ), 218
(51), 136 (22), 135 (82), 133 (33), 115 (73), 98 (42), 84 (86), 83
(27) [Calc. for C14H19FN (M ϩ H): 220.1501. Found: m/z,
220.1461].
(Z)-isomer: mp 40.0–42.0 ЊC; ν(KBr)/cmϪ1 2979, 2897, 2869,
1693, 1679, 1594, 1506, 1482, 1444, 1403, 1349, 1328, 1257,
1162, 1083, 1018, 903, 869, 852, 818, 753 and 698; δH(CDCl3)
1.28 (3H, t, J 6.8 Hz), 3.62 (2H, q, J 6.8 Hz), 4.15 (2H, d, J 15.1
Hz), 5.81 (1H, d, J 38.6 Hz), 7.25–7.63 (9H, m); m/z 256 (76%,
Mϩ), 211 (33), 196 (46), 191 (57), 185 (100), 179 (36), 178 (55)
(Found: C, 79.42; H, 6.70%).
3-Fluoro-2H-chromene 8
To a suspension of CsF (65.5 mg, 0.43 mmol), Si(OEt)4 (72.0
µL, 0.32 mmol), and salicylaldehyde (26.0 µL, 0.25 mmol) in
DMF at room temperature under argon atmosphere was added
α-fluorovinyltriphenylphosphonium triflate 4 (114 mg, 0.25
mmol) in one portion. After being heated to 130 ЊC the reaction
mixture was stirred for 40 h at that temperature. After usual
work-up, the residual oil was chromatographed on silica gel
(hexane as eluent) to give the desired product (12.9 mg, 34%) as
a colorless oil, which generally turned yellow on storage under
an argon atmosphere: ν(neat)/cmϪ1 3068, 2959, 2849, 1695,
1578, 1489, 1455, 1390, 1274, 1189, 1105, 1047, 1022, 879, 838,
752 and 658; δH(CDCl3) 4.81 (1H, d, J 1.0 Hz), 4.82 (1H, d,
J 1.5 Hz), 6.04 (1H, dt, J 1.0, 12.2 Hz), 6.81 (1H, dd, J 2.0, 7.8
Hz), 6.87 (1H, dd, J 2.0, 7.8 Hz), 6.94 (1H, dt, J 2.0, 7.8 Hz),
7.07 (1H, dt, J 2.0, 7.8 Hz); m/z 150 (100%, Mϩ), 131 (26), 121
(28), 101 (38), 96 (33), 75 (34), 74 (24), 63 (21) (Found: Mϩ,
150.0467. Calc. for C9H7FO: M, 150.0481).
(E)- and (Z)-1-(4Ј-Cyanophenyl)-3-ethoxy-2-fluoropropene 5e
Total yield 69%. (E)-isomer: ν(neat)/cmϪ1 2964, 2904, 2229,
1684, 1559, 1411, 1259, 1097, 1018, 869, 819 and 703;
δH(CDCl3) 1.26 (3H, t, J 6.8 Hz), 3.59 (2H, q, J 6.8 Hz), 4.15
(2H, d, J 23.4 Hz), 6.44 (1H, d, J 19.1 Hz), 7.39 (2H, d, J 8.3
Hz), 7.64 (2H, d, J 8.3 Hz); m/z 205 (28%, Mϩ), 177 (43), 160
(56), 158 (46), 156 (32), 148 (33), 140 (100), 134 (99), 133 (43),
130 (37), 129 (99), 128 (77), 116 (99), 101 (39), 75 (34) (Calc. for
C12H12FNO: C, 70.23; H, 5.89. Found: C, 70.31; H, 5.99%).
(Z)-isomer: ν(neat)/cmϪ1 2964, 2904, 2226, 1559, 1414, 1259,
1098, 1018, 865, 820 and 702; δH(CDCl3) 1.28 (3H, t, J 6.8 Hz),
3.62 (2H, q, J 6.8 Hz), 4.14 (2H, d, J 12.7 Hz), 5.82 (1H, d,
J 37.6 Hz), 7.58 (2H, d, J 8.8 Hz), 7.62 (2H, d, J 8.8 Hz); m/z
205 (37%, Mϩ), 177 (44), 161 (26), 160 (64), 158 (45), 148 (31),
140 (100), 134 (93), 133 (40), 130 (35), 129 (89), 128 (66), 116
(91), 101 (35), 75 (31) (Found: C, 69.87; H, 5.99%).
(E)- and (Z)-3-Ethoxy-2-fluoro-1-(2Ј-naphthyl)propene 5f
3-Fluoro-8-methoxy-2H-chromene 9
Total yield 77%. (E)-isomer: ν(neat)/cmϪ1 3055, 2977, 2871,
1681, 1598, 1557, 1507, 1380, 1273, 1182, 1138, 1097, 1018, 900,
868, 818 and 743; δH(CDCl3) 1.25 (3H, t, J 6.8 Hz), 3.60 (2H, q,
J 6.8 Hz), 4.25 (2H, d, J 23.4 Hz), 6.60 (1H, d, J 20.0 Hz), 7.36–
7.84 (7H, m); m/z 230 (93%, Mϩ), 201 (38), 186 (39), 185 (59),
47% Yield. ν(neat)/cmϪ1 2963, 2836, 1694, 1580, 1483, 1329,
1278, 1204, 1140, 1102, 1078, 1035, 971, 849, 730 and 641;
δH(CDCl3) 3.87 (3H, s), 4.87 (1H, d, J 1.0 Hz), 4.88 (1H, d, J 1.5
Hz), 6.04 (1H, dt, J 1.0, 10.3 Hz), 6.61 (1H, dd, J 1.5, 7.3 Hz),
6.76 (1H, dd, J 1.5, 8.3 Hz), 6.86 (1H, ddd, J 1.0, 7.3, 8.3 Hz);
106
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m/z 180 (100%, Mϩ), 179 (78), 149 (22), 137 (75), 109 (52), 101
(21), 89 (21), 83 (71), 75 (21), 63 (46), 62 (21) (Found: Mϩ,
180.0587. Calc. for C10H9FO: M, 180.0617).
(m, 10 H); m/z 246 (14%, Mϩ), 201 (43), 186 (38), 185 (100), 184
(21), 183 (88), 152 (35), 107 (21), 78 (21), 77 (64) (Calc. for
C14H12FOP: C, 68.29; H, 4.91. Found: C, 68.30; H, 4.91%).
2-Fluoro-3H-naphtho[2,1-b]pyran 10
Acknowledgements
31% Yield. Mp 38.1–39.5 ЊC; ν(neat)/cmϪ1 3034, 2849, 1683,
1631, 1506, 1230, 1185, 1083, 1032, 889, 814 and 749;
δH(CDCl3) 4.91 (1H, d, J 2.0 Hz), 4.92 (1H, d, J 1.5 Hz), 6.72
(1H, d, J 12.0 Hz), 7.09 (1H, d, J 9.3 Hz), 7.36 (1H, ddd, J 1.0,
6.8, 9.3 Hz), 7.48 (1H, ddd, J 1.0, 6.8, 9.3 Hz), 7.62 (1H, d,
J 9.3 Hz), 7.76 (1H, d, J 9.3 Hz), 7.80 (1H, d, J 9.3 Hz); m/z 200
(100%, Mϩ), 199 (98), 171 (34), 170 (54), 153 (39), 152 (27)
(Found: Mϩ, 200.0638. Calc. for C13H9FO: M, 200.0637).
This work was supported by the Mitsubishiyuka Foundation,
the Yamanouchi Foundation, and a Grant-in-Aid for Scientific
Research (10650836) from the Ministry of Education, Science,
Sports, and Culture. We thank Central Glass Co., Ltd. for a gift
of TfOH, which was used for the preparation of diphenyl-
iodonium triflate. We also thank Chemetall Japan Co., Ltd. for
a gift of CsF.
3-Fluoro-6-nitro-2H-chromene 11
References
14% Yield. Mp 129.2–130.5 ЊC; ν(KBr)/cmϪ1 2917, 1699, 1615,
1583, 1505, 1404, 1338, 1261, 1208, 1154, 1093, 1027, 906, 849,
829, 748, 725, 699 and 625; δH(CDCl3) 4.98 (2H, d, J 1.5 Hz),
6.12 (1H, d, J 11.1 Hz), 6.87 (1H, d, J 8.8 Hz), 7.86 (1H, d, J 2.4
Hz), 7.99 (1H, dd, J 2.4, 8.8 Hz); m/z 195 (94%, Mϩ), 194 (100),
149 (11), 148 (34), 120 (14), 101 (45), 83 (11), 75 (33), 74
(13) [Found: (Mϩ ϩ H), 196.0423. Calc. for C9H7FNO3: m/z,
196.0410].
1 B. E. Smart, Chem Rev., 1996, 96, 1555; G. Resnati and V. A.
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55, 5033.
3-Fluorochromane 12
To a solution of 23.9 mg of 3-fluoro-2H-chromene 8 (0.159
mmol) in 5 mL of ethyl acetate was added a catalytic amount
of 5% Rh–Al2O3. Hydrogenation at atmospheric pressure was
conducted for 16 h at room temperature. After usual work-up,
the residual oil was chromatographed on silica gel (hexane–
diethyl ether 100:1 as eluent) gave the desired product (17.6 mg,
73%), ν(neat)/cmϪ1 2964, 1585, 1491, 1463, 1346, 1302, 1265,
1233, 1183, 1117, 1094, 1063, 1026, 1008, 948, 828, 785 and 756;
δH(CDCl3) 2.95–3.25 (2H, m), 4.0–4.25 (1H, m), 4.25–4.40 (1H,
m), 5.12 (1H, ddq, J 2.0, 47.4, 4.4 Hz), 6.86 (1H, dd, J 1.0, 7.3
Hz), 6.92 (1H, dt, J 1.0, 7.3 Hz), 7.07 (1H, dd, J 1.0, 7.3 Hz),
7.13 (1H, dt, J 1.0, 7.3 Hz); m/z 152 (100%, Mϩ), 131 (31), 106
(44), 78 (56), 77 (22) (Found: Mϩ, 152.0623. Calc. for C9H9FO:
M, 152.0638).
9 H. F. Koch and A. J. Kielbania, Jr, J. Am. Chem. Soc., 1970, 92,
729.
10 E. J. Corey and M. A. Tius, Tetrahedron Lett., 1980, 21, 3535.
11 J. R. Shutt and S. Trippett, J. Chem. Soc. C, 1969, 2038.
12 L. Cassar and M. Foá, J. Organomet. Chem., 1974, 74, 75; G. Wittig
and H. Matzura, Angew. Chem., Int. Ed. Engl., 1964, 3, 231;
D. Seyferth and J. M. Burlitch, J. Org. Chem., 1963, 28, 2463.
13 T. Kitamura, M. Yamane, B.-X. Zhang and Y. Fujiwara, Bull.
Chem. Soc. Jpn., 1998, 71, 1215; T. Kitamura, M. Yamane,
R. Furuki, H. Taniguchi and M. Shiro, Chem. Lett., 1993, 1703.
14 J. Ichikawa, Y. Wada, T. Okauchi and T. Minami, Chem. Commun.,
1997, 1537; J. Ichikawa, M. Kobayashi, Y. Noda, N. Yokota, K.
Amano and T. Minami, J. Org. Chem., 1996, 61, 2763; L.
Strekowski, A. S. Kiselyov and M. Hojjat, J. Org. Chem., 1994, 59,
5886; K. Burger and B. Helmreich, J. Chem. Soc., Chem. Commun.,
1992, 348; H. L. Sham and D. A. Betebenner, J. Chem. Soc., Chem.
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15 F. Camps, J. Coll, A. Messeguer and M. A. Pericás, J. Heterocycl.
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16 F. M. Dean, in The Total Synthesis of Natural Products, ed. J.
ApSimon, Wiley, New York, 1973, vol. 1, p. 467.
17 A general preparation of substituted 2H-chromenes from
vinyltriphenylphosphonium bromide and salicylaldehyde derivatives
has been studied by Schweizer et al.: E. E. Schweizer, J. Am. Chem.
Soc., 1964, 86, 2744; E. E. Schweizer, J. Liter and D. J. Monaco,
J. Org. Chem., 1968, 33, 2416.
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19 T. Yasunaga, R. Naito, T. Kontani, S. Tsukamoto, T. Nomura,
T. Yamaguchi and T. Mase, J. Med. Chem., 1997, 40, 1252.
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1991, 32, 2735.
8-Methoxychromane 13
To a solution of 15.9 mg of 3-fluoro-8-methoxy-2H-chromene 9
(0.088 mmol) in 2 mL of EtOH was added a catalytic amount
of PtO2. Hydrogenation at atmospheric pressure was conducted
for 16 h at room temperature. After usual work-up, the residual
oil was chromatographed on silica gel (hexane–diethyl ether
10:1 as eluent) gave the desired product (9.2 mg, 63%), ν(neat)/
cmϪ1 2964, 1261, 1094, 1019, 866 and 800; δH(CDCl3) 1.97–2.06
(2H, m), 2.79 (2H, t, J 6.3 Hz), 3.86 (3H, s), 4.27 (2H, t, J 5.4
Hz), 6.65–6.82 (3H, m); m/z 164 (100%, Mϩ), 149 (55), 136 (40),
135 (39), 121 (41), 107 (36), 103 (41), 93 (37), 91 (55), 78 (34), 77
(59), 65 (49) [lit.,22 m/z 164 (100%, Mϩ), 150 (12), 149 (23), 136
(16), 135 (12), 133 (5), 122 (4), 121 (25), 108 (5), 107 (10), 105
(7), 91 (9), 79 (5), 78 (6.5), 77 (16), 65 (16), 51 (9)].
ꢀ-Fluorovinyldiphenylphosphine oxide 15
To a solution of α-fluorovinyldiphenylphosphine 2 (51.8 mg,
0.22 mmol) in acetone (1 mL) was added 30% aq. hydrogen
peroxide (0.1 mL) at 0 ЊC. After the mixture had been stirred for
30 min, the reaction was quenched with aq. NaHSO3. The mix-
ture was extracted with diethyl ether, then the ethereal solution
was dried over MgSO4. After removal of the solvent, the
remaining oil was separated by column chromatography (silica
gel; hexane–EtOAc 1:1) to give the desired product (46.4 mg,
84%), mp 83.5–84.5 ЊC; ν(KBr)/cmϪ1 3096, 3055, 3021, 2959,
1632, 1588, 1489, 1435, 1336, 1319, 1203, 1179, 1121, 1097, 998,
913, 801, 757, 729, 712, 689 and 658; δH(CDCl3) 5.72 (1H, ddd,
J 3.9, 22.0, 23.0 Hz), 5.82 (1H, ddd, J 3.9, 6.4, 51.3 Hz), 7.3–7.9
21 T. Minami, H. Sako, T. Ikehira, T. Hanamoto and I. Hirao,
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22 B. Willhalm, A. F. Thomas and F. Gautschi, Tetrahedron, 1964, 20,
1185.
Paper a905878h
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