A novel approach of cycloaddition of difluorocarbene to α-β-unsaturated aldehydes and ketones: Synthesis of gem-difluorocyclopropyl ketones and 2-fluorofurans

Article abstract of DOI:10.1039/b212232d

A series of gem-difluorocyclopropyl acetals and ketals are easily obtained in moderate yields from the [1 + 2] cycloaddition of difluorocarbene to 1,3-dioxolanes of α,β-unsaturated aromatic aldehydes and ketones. Hydrolysis of these fluorinated compounds under acidic conditions either gives the corresponding gem-difluorocyclopropyl ketones or 1-aryl-2-fluorofuran derivatives through intramolecular carbonium rearrangement with simultaneous ring cleavage.

Full text of DOI:10.1039/b212232d

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A novel approach of cycloaddition of difluorocarbene to
ꢀ,ꢁ-unsaturated aldehydes and ketones: synthesis of
gem-difluorocyclopropyl ketones and 2-fluorofurans
Wei Xu and Qing-Yun Chen*
Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, 200032 Shanghai, China.
E-mail: chenqy@pub.sioc.ac.cn
Received 12th December 2002, Accepted 19th February 2003
First published as an Advance Article on the web 11th March 2003
A series of gem-difluorocyclopropyl acetals and ketals are easily obtained in moderate yields from the [1ϩ2]
cycloaddition of difluorocarbene to 1,3-dioxolanes of α,β-unsaturated aromatic aldehydes and ketones. Hydrolysis of
these fluorinated compounds under acidic conditions either gives the corresponding gem-difluorocyclopropyl ketones
or 1-aryl-2-fluorofuran derivatives through intramolecular carbonium rearrangement with simultaneous ring
cleavage.
Introduction
Difluorocarbene addition to an olefin is a fundamental
reaction for the preparation of difluorocyclopropane deriv-
atives.1 Although electron-rich alkenes react readily with
difluorocarbene under mild conditions, there are only a few
difluorocarbene reagents that have been found to react with
Scheme 1 X = H, R = H (a); X = Cl, R = H (b); X = CH3O, R = H (c);
electron-deficient alkenes to give reasonable yields of gem-
X = CH3, R = H (d); X = CF3, R = H (e); X = H, R = CH3 (f ); X = Cl,
difluorocyclopropanes.2 Using electron-poor steroidal enones
R = CH3 (g); X = CH3O, R = CH3 (h); X = CH3, R = CH3 (i); X = CF3,
and dienones, Beard et al. first carried out their cycloaddition
with difluorocarbene generated from high temperature (150–
180 ЊC) thermolysis of a large excess (50 equiv.) of sodium
chlorodifluoroacetate.3 Due to the inconvenience and low yields
of this method, Kobayashi et al. prepared gem-difluorocyclo-
propyl ketones through a three-step procedure, i.e. addition of
difluorocarbene to the allyl acetate, alkaline hydrolysis and
Jones oxidation, instead of the direct difluoromethylenation of
α,β-unsaturated ketones.4 Recently, a highly efficient difluoro-
carbene precursor, FSO2CF2COOSiMe3 (TFDA) was reported,
by which an unprecedented difluorocarbene addition to elec-
tron-poor n-butyl acrylate proceeded in 73% yield.5 The
superiority of the new reagent over ClCF2COONa was also
demonstrated in the synthesis of bis- and oligo-gem-difluoro-
cyclopropanes.6 However, we found that TFDA did not react
with α,β-unsaturated aldehydes and ketones under the reaction
conditions used (i.e. in the presence of 10 mol% of NaF in
diglyme at 120 ЊC).7 It is not surprising that the nucleophilic
character of the enone carbon–carbon double bond is con-
siderably reduced by electron delocalization with the carbonyl
group, resulting in lower reactivity towards the electrophilic
difluorocarbene species.8 In order to overcome the difficulty, a
protection and deprotection of enone carbonyl group might be
an alternative choice.
R = CH3 (j); X = CH3O, R = C6H5 (k); X = CH3, R = C6H5 (l); X = H,
R = C6H5 (m); X = Cl, R = C6H5 (n); X = CF3, R = C6H5 (o); X = C6H5,
R = 4-CH3–C6H4 (p); X = C6H5, R = 4-CH3O–C6H4 (q).
The results are listed in Table 1.
Unexpectedly, the following deprotection step was not easy.
Employing usual deprotection conditions for 1,3-dioxolanes,
e.g. HCl–acetone/rt, HCl–methanol/rt, HCl–THF/rt, 2 could
not be converted to the corresponding aldehydes and ketones
and were recovered completely. Interestingly, it was found that
deprotection was achieved by treatment with saturated oxalic
acid solution in dioxane at 110 ЊC for 6 h.9 The products based
1
19
on H, F NMR, MS as well as elemental analysis were gem-
difluorocyclopropyl ketones (3) and /or 1-aryl-2-fluorofurans
(4) (Scheme 2).
Scheme 2
The results are listed in Table 2.
We, herein, present the results of cycloaddition of difluoro-
carbene generated from decomposition of TFDA to protected
α,β-unsaturated aldehydes and ketones followed by deprotec-
tion with acidic hydrolysis.
Compound 4k was crystallized from a mixture of petroleum
ether and dichloromethane, and its structure was confirmed by
single crystal X-ray analysis (Fig. 1).
The results shown in Table 2 demonstrated that the normal
products 3 after acidic hydrolysis were obtained for almost all
of the β-aryl-gem-difluorocyclopropyl ketals (Table 2, entries
13–17) except for those compounds having an electron-
donating group (CH3O, CH3) on the β-phenyl ring (Table 2,
entries 11,12). 1-Aryl-2-fluorofurans (4) were the only isolated
products derived from the hydrolysis of β-aryl gem-difluoro-
cyclopropylacetals (2, R = H) (Table 2, entries 1–4) except
the compound possessing a strong electron withdrawing group
Results and discussion
Treatment of 1,3-dioxolanes of α,β-unsaturated aromatic alde-
hydes and ketones (1) with TFDA (3 equiv.) in diglyme in the
presence of 10 mol% anhydrous NaF at 110–130 ЊC for about 2
h gave the corresponding [1ϩ2] adducts (2) in moderate to good
yields (Scheme 1).
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 1 5 1 – 1 1 5 6
1151

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Table 1 Cycloaddition of difluorocarbene to acetals and ketals of α,β-unsaturated aromatic aldehydes and ketones
Entry
Substrate
X
R
T /ЊCa
Time/h
Product
Isolated yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
H
Cl
CH3O
CH3
CF3
H
H
H
H
H
H
CH3
CH3
CH3
118
126
124
120
128
112
118
115
122
124
120
122
118
128
126
128
132
1
2
0.5
1
1
0.5
2
0.5
1
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
68
59
72
67
51
49
48
54
62
42
61
65
42
48
40
60
64
Cl
CH3O
CH3
CF3
CH3O
CH3
H
CH3
CH3
2
C6H5
C6H5
C6H5
C6H5
C6H5
4-CH3C6H4
4-CH3OC6H4
0.5
1.5
1
1
1
0.5
2
Cl
CF3
C6H5
C6H5
a Oil bath temperature
Table 2 Hydrolysis of gem-difluorocyclopropyl acetals and ketals with saturated oxalic acid solution in dioxane at 110 ЊC for 6 h
Entry
Substrate
X
R
Product
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
H
Cl
CH3O
CH3
CF3
H
H
H
H
H
H
CH3
CH3
CH3
4a
21
21
26
27
4b
4c
4d
4e, 3e
4f
4g, 3g
4h
4i
3j
4k
4l, 3l
3m
3n
3o
4p, 3p
4q, 3q
1 (4e), 55 (3e)
47
1(4g), 64 (3g)
52
50
69
55
15 (4l), 36 (3l)
78
54
43
2(4p), 60(3p)
2(4q), 58(3q)
Cl
CH3O
CH3
CF3
CH3O
CH3
H
CH3
CH3
C6H5
C6H5
C6H5
C6H5
C6H5
4-CH3C6H4
4-CH3OC6H4
Cl
CF3
C6H5
C6H5
carbonium ion (3ϩ) whose reactivity depends on the properties
of R and the substituent X on the β-phenyl ring (Scheme 3).
The carbocation of aldehyde (R = H) and methyl ketones
(R = CH3), (3ϩ) generated undergoes an intramolecular shift
easily with simultaneous collapse of the carbon–carbon bond
Fig. 1 X-Ray structure of 4k. Selected bond lengths (Å), bond angles
(Њ) and torsion angles (Њ): C (1)–C(2), 1.351(2); C(1)–C(11), 1.4474 (19);
C(2)–C(3), 1.391(2); O(1)–C(1), 1.3770(16); O(1)–C(4), 1.3740(16); F–
C(2), 1.3525(17); C(2)–C(3), 1.391(2); C(3)–C(4), 1.347(2); C(4)–C(5)
1.4523(19); C(4)–O(1)–C(1), 108.35(11); C(14)–O(2)–C(17), 117.70(13);
C(2)–C(1)–O(1), 106.03(12); C(1)–C(2)–F, 124.62(14); F–C(2)–C(3),
124.79(14).
(CF3) at the para position of the β-phenyl ring (Table 2, entry
5), As for the β-aryl-gem-difluorocyclopropylmethyl ketals (2,
R = CH3), the ratio of normal products (3) to furan derivatives
(4) obtained is dependent on the electronic property of the sub-
stitute on the β-phenyl ring; i.e. for an electron-donating group,
furan derivatives (4, R = CH3, Table 2, entries 6, 8, 9) were the
sole products, whereas for an electron-withdrawing group, the
normal ketone was dominantly, if not exclusively, produced
(Table 2, entries 5, 7, 10).
All these results might be rationalized as follows: after depro-
tection of 2, β-aryl-gem-difluorocyclopropyl aldehydes and
ketones (3) might be protonated on carbonyl oxygen to give a
Scheme 3 Proposed mechanism.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 1 5 1 – 1 1 5 6
1152

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opposite to the gem-difluoromethyl group10 followed by an
attack of enol oxygen on the resultant carbonium ion 5 (Y = H)
to yield β-fluorofuran derivatives after HF elimination (Path a).
An alternative mechanism suggested by one of the referees of
this manuscript is that cyclopropane ring opening occurs dur-
ing the protonation of 2 with the direct formation of a new
cation 5 (Y = CH2CH2OH) instead of 3ϩ (Path b).
This process, apparently, proceeds readily when the substi-
tuent on the β-phenyl ring is an electron-donating or even a
weak electron-withdrawing group (X = CH3, CH3O, H, Cl). On
the contrary, if a strong electron-withdrawing group (X = CF3,
Cl) is present on the β-phenyl ring, the carbocation intra-
molecular shift does not take place or proceeds with difficultly.
As for the aryl ketones (R = C6H5, p-CH3C6H4, p-CH3-
OC6H4), due to the participation of the aryl group, their carbo-
cations (3ϩ) are stable and do not rearrange, therefore, aryl
ketones are regenerated unless an electron-donating group
(CH3, CH3O) on the β-phenyl ring is present, in which case the
β-fluorofuran derivative is also formed and even becomes the
only product.
3.81 (s, 3H), 3.94–4.02 (m, 4H), 6.02 (d, J = 18.6 Hz, 1H), 6.65
(d, J = 15.9 Hz, 1H), 6.84–6.87 (m, 2H), 7.32–7.35 (m, 2H). MS
m/z (relative intensity) 220 (Mϩ, 7.59), 205 (100.00), 189 (1.82),
175 (2.87), 161 (40.34), 148 (11.09), 133 (14.93), 102 (3.57), 87
(13.04). Anal. Calcd for C13H16O3: C, 70.89; H, 7.32. Found, C,
70.92; H, 7.39%.
Compound 1i: yellow liquid, 88% yield. IR (film) (cmϪ1):
2987, 2885, 1515, 1373, 1297, 1197, 1100, 1074, 1042. 1H NMR
(CDCl3) δ 1.58 (s, 3H), 2.35 (s, 3H), 3.93–4.05 (m, 4H), 6.12 (d,
J = 16.2 Hz, 1H), 6.69 (d, J = 15.9 Hz, 1H), 7.14 (d, J = 7.8 Hz,
2H), 7.31 (d, J = 8.4 Hz, 2H). MS m/z (relative intensity) 204
(Mϩ, 1.53), 189 (100.00), 173 (0.89), 159 (2.93), 145 (35.95), 117
(16.36), 91 (10.09). Anal. Calcd for C13H16O2: C, 76.44; H, 7.90.
Found, C, 76.65; H, 8.31%.
Compound 1j: yellow liquid, 95% yield. IR (film) (cmϪ1):
2986, 2886, 1618, 1415, 1376, 1327, 1201, 1167, 1127, 1069,
1043. 1H NMR (CDCl3) δ 1.57 (s, 3H), 3.92–4.04 (m, 4H), 6.25
(d, J = 15.9 Hz, 1H), 6.74 (d, J = 15.9 Hz, 1H), 7.47–7.59 (m,
4H). MS m/z (relative intensity) 258 (Mϩ, 5.12), 243 (100.00),
199 (47.10), 171 (20.18), 87 (18.04). Anal. Calcd for
C13H13F3O2: C, 60.46; H, 5.07. Found: C, 60.51; H, 4.94%.
Compound 1k: solid, mp 76–77 ЊC, 75% yield. IR (film)
(cmϪ1): 2980, 2965, 2895, 1654, 1606, 1575, 1514, 1310, 1285,
1245, 1176, 1152, 1046, 1023. 1H NMR (CDCl3) δ 3.80 (s, 3H),
3.98–4.12 (m, 4H), 6.22 (d, J = 15.9 Hz, 1H), 6.61 (d, J = 15.9
Hz, 1H), 6.83 (d, J = 8.7 Hz, 2H), 7.30–7.37 (m, 5H), 7.54–7.57
(m, 2H). MS m/z (relative intensity) 282 (Mϩ, 10.82), 251 (1.20),
221 (51.04), 210 (100.00), 205 (25.77), 195 (11.03), 149 (30.15),
105 (34.19), 77 (21.94). Anal. Calcd for C18H18O3: C, 76.57; H,
6.43. Found: C, 76.53; H, 6.41%.
Compound 1l: solid, mp 61–62 ЊC, 77% yield. IR (film)
(cmϪ1): 2895, 1665, 1600, 1514, 1447, 1338, 1223, 1155, 1044.
1H NMR (CDCl3) δ 2.32 (s, 3H), 3.99–4.13 (m, 4H), 6.30 (d,
J = 16.2 Hz, 1H), 6.65 (d, J = 15.9 Hz, 1H), 7.09–7.58 (m, 9H).
MS m/z (relative intensity) 266 (Mϩ, 36.59), 251 (0.78), 221
(47.89), 207 (100.00), 194 (84.58), 189 (35.67), 179 (46.81), 145
(42.81), 105 (39.68), 91 (22.03), 77 (50.20). Anal. Calcd for
C18H18O2: C, 81.17; H, 6.81; Found: C, 81.04; H, 6.87%.
Compound 1n: pale yellow solid, mp 66–67 ЊC, 90% yield. IR
(film) (cmϪ1): 2890, 1658, 1592, 1489, 1332, 1219, 1160, 1049.
1H NMR (CDCl3) δ 3.96–4.14 (m, 4H), 6.33 (d, J = 15.9 Hz,
1H), 6.64 (d, J = 15.6 Hz, 1H), 7.23–7.60 (m, 9H). MS m/z
(relative intensity) 286 (Mϩ, 12.86), 241 (6.84), 214 (49.63), 189
(18.38), 179 (46.58), 165 (31.57), 149 (28.95), 105 (55.48), 77
(100.00). HRMS. Calcd for C17H15ClO2: 286.0761. Found:
286.0766.
The study on the reaction of simple α,β-unsaturated aliphatic
aldehydes and ketones (RCH᎐CHCRO, R = H, alkyl) with
᎐
TFDA is in progress.
In conclusion, we have developed a simple method for the
synthesis of β-aryl gem-difluorocyclopropyl ketones and 1-aryl-
2-fluorofurans from the reactions of protected α,β-unsaturated
aldehydes and ketones with an easily available difluorocarbene
precursor, FSO2CF2COOSiMe3.
Experimental section
1H NMR spectra were recorded with TMS as an internal
standard (positive for upfield). 19F NMR spectra were
recorded with CFCl3 as an external standard (negative for
upfield). The solvent for NMR measurement was CDCl3.
Diglyme was dried with sodium, FSO2CF2COOSiMe3 (TFDA)
was prepared according to the literature.5 Aldehydes are com-
mercially available, whereas all α,β-unsaturated ketones were
prepared following published procedures.11 1,3-Dioxane of
α,β-unsaturated aldehydes are prepared according to published
methods.12,13
Synthesis of 1,3-dioxane of ꢀ,ꢁ-unsaturated ketones14
A typical procedure: in a 250 ml flask equipped with a Dean–
Stark adaptor and a condenser was placed 4-phenyl-3-butene-
2-one (1.56 g, 10.7 mmol), ethylene glycol (9.3 ml), 2-ethyl-2-
methyl-1,3-dioxolane15 (9.3 ml), PTSA (93 mg) and benzene
(150 ml). The mixture was heated to reflux for 12 h. After the
mixture was cooled to room temperature, saturated Na2CO3
(20 ml) was added and stirred for 15 minutes. The organic layer
was separated and the aqueous was extracted with ether. The
combined organic phase was washed with brine and dried over
Na2SO4. The solvent was removed and the residue was purified
by flash chromatography on a silica gel column. Ketal 1f was
obtained as a pale yellow liquid (1.24 g, 61%) with spectro-
scopic data identical to that reported previously.16 Compound
1m (71% yield) was determined by the published spectroscopic
data.17
Compound 1o: white solid, mp 79–80 ЊC, 82% yield. IR (film)
(cmϪ1): 2897, 1664, 1615, 1448, 1416, 1324, 1168, 1110, 1067. 1H
NMR (CDCl3) δ 3.98–4.14 (m, 4H), 6.45 (d, J = 15.9 Hz,
19
1H), 6.73 (d, J = 15.6 Hz, 1H), 7.36–7.58 (m, 9H).
F
NMR (CDCl3) δ Ϫ62.5 (s, 3F). MS m/z (relative intensity)
320 (Mϩ, 45.41), 276 (17.89), 248 (52.70), 207 (19.99), 189
(27.60), 175 (19.98), 149 (85.63), 105 (100.00), 77 (77.41). Anal.
Calcd for C18H15F3O2: C, 67.50; H, 4.72. Found: C, 67.80; H,
4.40%.
Compound 1p, white solid, mp 70–71 ЊC, 82% yield. IR (film)
(cmϪ1): 2984, 2949, 2891, 1650, 1614, 1577, 1511, 1495, 1450,
1
1278, 1246, 1182, 1143, 1054, 1020. H NMR (CDCl3) δ 2.36
(s, 3H), 3.99–4.12 (m, 4H), 6.35 (d, J = 15.9 Hz, 1H), 6.69 (d,
J = 15.9 Hz, 1H), 7.17–7.49 (m, 9H). MS m/z (relative intensity)
266 (Mϩ, 21.26), 251 (0.95), 221 (51.04), 194 (100.00), 179
(55.16), 131(26.64), 119 (44.69). Anal. Calcd for C18H18O2: C,
81.17; H, 6.81. Found: C, 81.16; H, 6.91%.
Compound 1g: yellow liquid, 64%. IR (film) (cmϪ1): 2987,
2885, 1655, 1594, 1492, 1406, 1374, 1215, 1195, 1095, 1043.
1H NMR (CDCl3) δ 1.55 (s, 3H), 3.93–4.02 (m, 4H), 6.13 (d,
J = 16.2 Hz, 1H), 6.66 (d, J = 16.5 Hz, 1H), 7.26–7.31 (m, 4H).
MS m/z (relative intensity) 224 (Mϩ, 5.14), 209 (100.00), 174
(1.54), 165 (41.73), 137 (14.92), 102 (13.16), 87 (13.04). Anal.
Calcd for C12H13ClO2: C, 64.15; H, 5.83. Found, C, 64.33; H,
6.50%.
Compound 1q: colorless liquid, 42%. 1H NMR (CDCl3)
δ 3.81 (s, 3H), 3.97–4.13 (m, 4H), 6.35 (d, J = 15.9 Hz, 1H), 6.67
(d, J = 15.9 Hz, 1H), 6.88–6.91 (m, 2H), 7.23–7.40 (m, 5H),
7.47–7.50 (m, 2H). MS m/z (relative intensity) 282 (Mϩ, 15.17),
210 (100.00), 205 (7.91), 179 (18.50), 175 (9.25), 131 (8.21), 103
(11.11), 77 (19.22). Anal. Calcd for C18H18O3: C, 76.57; H, 6.43.
Found: C, 81.16; H, 6.91%.
Compound 1h: white solid, mp 50–51 ЊC, 65% yield. IR (film)
(cmϪ1): 2989, 2934, 2896, 1655, 1606, 1578, 1512, 1442, 1307,
1274, 1247, 1175, 1101, 1031. 1H NMR (CDCl3) δ 1.56 (s, 3H),
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 1 5 1 – 1 1 5 6
1153

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(100.00). HRMS. Calcd for C13H14F2O2: 240.0962, Found
Synthesis of gem-difluoropropyl acetals and ketals
240.0925.
A typical procedure: under a nitrogen atmosphere, in a 10 ml
side-armed Pyrex tube with a magnetic stirring bar and a pres-
sure-equalized addition funnel, was placed acetal (1a) (1.82 g,
10.33 mmol), sodium fluoride (43 mg, 1.03 mmol) and diglyme
(1 ml). After heating the mixture to about 120 ЊC (bath), TFDA
(7.76 g, 30.98 mmol) was added dropwise. The mixture
was stirred at this temperature for 1 h. Then the reaction was
cooled to room temperature and directly purified by flash
chromatography on a silica gel column. Title product (2a)
(1.60 g, 68%) was obtained as a pale yellow liquid (eluent: pet-
roleum ether–ether = 10 : 1).
Compound 2g: liquid, IR (film) (cmϪ1): 2988, 1891, 1672,
1
1612, 1593, 1493, 1464, 1220, 1091, 1039. H NMR (CDCl3)
δ 1.35 (s, 3H), 2.07–2.15 (m, 1H), 2.87–2.94 (m, 1H), 3.91–4.06
(m, 4H), 7.12–7.33 (m, 4H). 19F NMR (CDCl3) δ Ϫ133.8 (dd,
J = 159.3, 15.2 Hz, 1 F), Ϫ136.5 (dd, J = 159.0, 14.1 Hz, 1 F).
MS m/z (relative intensity) 274 (Mϩ, 2.19), 259 (1.78), 209
(12.75), 165 (14.64), 101 (8.89), 87 (100.00). HRMS. Calcd for
C13H13ClF2O2: 274.0572, Found 274.0587.
Compound 2h: liquid, IR (film) (cmϪ1): 2989, 2895, 1614,
1519, 1466, 1250, 1180, 1037. 1H NMR (CDCl3) δ 1.55 (s, 3H),
2.03–2.11 (m, 1H), 2.85–2.93 (m, 1H), 3.79 (s, 3H), 3.92–4.06
Compound 2a: liquid, IR (film) (cmϪ1): 2893, 1679, 1504,
(m, 4H), 6.85–6.88 (m, 2 H), 7.14–7.17 (d, J = 8.7 Hz, 2 H). 19
F
1
1475, 1448, 1259, 1217, 1176, 1021, 1003. H NMR (CDCl3)
NMR (CDCl3) δ Ϫ135.0 (dd, J = 158.4, 14.7 Hz, 1 F), Ϫ137.5
(dd, J = 158.3, 13.8 Hz, 1 F). MS m/z (relative intensity) 270
(Mϩ, 1.12), 255 (1.96), 235 (1.58), 183 (3.99), 163 (6.84), 87
(100.00). HRMS. Calcd for C14H16F2O3: 270.1068, Found
270.1063.
δ 2.10–2.16 (m, 1H), 2.85–2.91 (m, 1H), 3.90–4.06 (m, 4H), 5.00
(d, J = 6.0 Hz, 1 H), 7.24–7.34 (m, 5H). 19F NMR (CDCl3)
δ Ϫ134.6 (dd, J = 163.3, 15.8 Hz, 1 F), Ϫ137.0 (dd, J = 164.4,
15.5 Hz, 1 F). MS m/z (relative intensity) 226 (Mϩ, 1.60), 207
(1.56), 183 (0.58), 164 (4.83), 153 (2.97), 133 (16.04), 77 (6.51),
73 (100.00). HRMS. Calcd for C12H12F2O2: 226.0805, Found
226.0805.
Compound 2i: pale yellow liquid, IR (film) (cmϪ1): 2988,
2891, 1522, 1466, 1410, 1378, 1328, 1278, 1244, 1221, 1172,
1039, 993. 1H NMR (CDCl3) δ 1.55 (s, 3H), 2.11 (dddd,
J = 14.7, 8.7, 1.2 Hz, 1H), 2.90 (dddd, J = 14.7, 9.0, 1.2 Hz, 1H),
3.90–4.07 (m, 4H), 7.3 (s, 4H). 19F NMR (CDCl3) δ Ϫ133.7 (dd,
J = 159.0, 14.7 Hz, 1F), Ϫ136.0 (dd, J = 157.4, 14.4 Hz, 1F). MS
m/z (relative intensity) 254 (Mϩ, 2.60), 239 (2.08), 189 (1.94),
167 (2.10), 147 (5.79), 115 (4.80), 87 (100.00). HRMS. Calcd for
C14H16F2O2: 254.1118, Found: 254.1102. Anal. Calcd for
C14H16F2O2: F, 14.94. Found: F, 15.14%.
Compound 2b: liquid, IR (film) (cmϪ1): 2894, 1683, 1500,
1400, 1260, 1176, 1093, 1004. 1H NMR (CDCl3) δ 2.05–2.14 (m,
1H), 2.81–2.97 (m, 1H), 3.90–4.06 (m, 4H), 4.46 (d, J = 8.1 Hz,
0.31 H), 4.99 (d, J = 5.7 Hz, 0.69 H), 7.17–7.39 (m, 4H). 19F
NMR (CDCl3) δ Ϫ134.6 (dd, J = 163.3, 15.8 Hz, 1 F), Ϫ137.0
(dd, J = 164.4, 15.5 Hz, 1 F). MS m/z (relative intensity) 260
(Mϩ, 0.55), 225 (1.76), 187 (3.67), 165 (17.66), 137 (10.63), 131
(50.33), 103 (25.60), 73 (100.00). HRMS. Calcd for
C12H11ClF2O2: 260.0416, Found 260.0371. Anal. Calcd for
C12H11F2O2: C, 55.29; H, 4.25; F, 14.58. Found: C, 55.49; H,
4.24; F, 14.36%.
Compound 2j: liquid, IR (film) (cmϪ1): 2990, 1620, 1468,
1
1169, 1127, 1068. H NMR (CDCl3) δ 1.55 (s, 3H), 2.15–2.23
(m, 1H), 2.95–3.03 (m, 1H), 3.92–4.09 (m, 2H), 7.34–7.60 (m,
4H). 19F NMR (CDCl3) δ Ϫ62.5 (s, 3F), Ϫ133.3 (dd, J = 161.0,
14.4 Hz, 1F), Ϫ136.7 (dd, J = 160.5, 13.5 Hz, 1F). MS m/z
(relative intensity) 308 (Mϩ, 1.68), 293 (6.87), 243 (100.00), 199
(49.54), 171 (18.43), 145 (11.73), 87 (93.49). Anal. Calcd for
C19H18F2O3: C, 68.67; H, 5.46; F, 11.43. Found: C, 68.67; H,
5.42; F, 11.61%.
Compound 2c: pale yellow liquid, IR (film) (cmϪ1): 2897,
1614, 1519, 1251, 1178, 1033. 1H NMR (CDCl3) δ 2.04–2.10 (m,
1H), 2.79–2.87 (m, 1H), 3.78 (s, 3H), 3.90–4.08 (m, 4H), 4.49
(d, J = 8.1 Hz, 0.32 H), 4.97 (d, J = 6.3 Hz, 0.68 H), 6.84–6.87
(m, 2H), 7.16–7.36 (m, 2H). 19F NMR (CDCl3) δ Ϫ122.5 (dd,
J = 165.3, 14.4 Hz, 0.32 F), Ϫ134.9 (dd, J = 159.0, 13.5 Hz, 0.68
F), Ϫ137.1 (dd, J = 163.6, 13.5 Hz, 0.68 F), Ϫ145.8 (d, J = 165.0
Hz, 0.32 F). MS m/z (relative intensity) 256 (Mϩ, 1.73), 183
(4.48), 139 (49.32), 77 (8.52), 73 (100.00). Anal. Calcd for
C13H14F2O3: C, 60.93; H, 5.51; F, 14.83. Found: C, 60.59; H,
6.02; F, 14.55%.
Compound 2k: white solid, mp 59–60 ЊC. IR (film) (cmϪ1):
2895, 1654, 1513, 1460, 1421, 1285, 1245, 1152, 1046. 1H NMR
(CDCl3) δ 2.26–2.33 (m, 1H), 3.09–3.17 (m, 1H), 3.76 (s, 3H),
3.83–4.18 (m, 4H), 6.79–6.83 (m, 2H), 7.05–7.09 (m, 2H). 19F
NMR (CDCl3) δ Ϫ133.3 (dd, J = 158.1, 14.5 Hz, 1F), 136.7 (dd,
J = 158.3, 14.3 Hz, 1F). MS m/z (relative intensity) 332 (Mϩ,
1.11), 238 (2.30), 210 (16.79), 205 (4.99), 149 (100.00), 105
(31.77), 77 (21.96). Anal. Calcd for C19H18F2O3: C, 68.67; H,
5.46; F, 11.43. Found: C, 68.67; H, 5.42; F, 11.61%.
Compound 2d: pale yellow liquid, IR (film) (cmϪ1): 2959,
2893, 1521, 1473, 1402, 1328, 1259, 1220, 1175, 1098, 1026,
1004. 1H NMR(CDCl3) δ 2.05–2.14 (m, 1H), 2.33 (s, 3H), 2.81–
2.88 (m, 1H), 3.90–4.07 (m, 4H), 4.98 (d, J = 6.0 Hz, 1H), 7.15
(s, 4H). 19F NMR (CDCl3) δ Ϫ134.3 (dd, J = 159.6 Hz, 15.2 Hz,
1F), Ϫ136.6 (dd, J = 159.3 Hz, 14.4 Hz, 1F). MS m/z (relative
intensity) 240 (Mϩ, 1.04), 225 (0.33), 167 (1.37), 147 (4.97), 73
(100.00). Anal. Calcd for C13H14F2O2: C, 64.99; H, 5.87; F,
15.82. Found: C, 65.07; H, 5.96; F, 15.84%.
Compound 2l: solid, mp 40–41 ЊC. IR (film) (cmϪ1): 2895,
1654, 1513, 1460, 1421, 1285, 1245, 1152, 1046. 1H NMR
(CDCl3) δ 2.30 (s, 3H), 2.31–2.37 (m, 1H), 3.11–3.19 (m, 1H),
3.83–4.18 (m, 4H), 7.03–7.08 (m, 4H), 7.33–7.41 (m, 3H), 7.54–
7.58 (m, 2H). 19F NMR (CDCl3) δ Ϫ132.3 (dd, J = 157.9, 14.7
Hz, 1F), Ϫ135.4 (dd, J = 158.5, 13.3 Hz, 1F). MS m/z (relative
intensity) 316 (Mϩ, 3.04), 266 (28.87), 239 (0.80), 194 (70.88),
149 (100.00), 105 (91.34), 77 (60.80). Anal. Calcd for
C19H18F2O2: C, 72.14; H, 5.74; F, 12.01. Found: C, 72.48; H,
5.92; F, 12.02%.
Compound 2e: yellow liquid, IR (film) (cmϪ1): 2964, 2897,
1686, 1623, 1584, 1525, 1476, 1413, 1329, 1262, 1169, 1127,
1
1070, 1021. H NMR(CDCl3) δ 2.12–2.22 (m, 1H), 2.89–2.97
(m, 1H), 3.83–4.10 (m, 4H), 7.35–7.60 (m, 4H). 19F NMR
(CDCl3) δ Ϫ134.1 (dd, J = 161.6 Hz, 13.0 Hz, 1F), Ϫ136.2 (dd,
J = 162.7, 13.8 Hz, 1F), Ϫ62.60 (s, 3F). MS m/z (relative inten-
sity) 294 (Mϩ, 0.55), 293 (0.61), 275 (2.23), 232 (1.78), 221
(1.73), 201 (6.48), 145 (2.24), 73 (100.00), 69 (2.03). Anal. Calcd
for C13H11F5O2: C, 53.07; H, 3.77; F, 32.29. Found: C, 52.60; H,
3.63; F, 32.53%.
Compound 2m: yellow liquid, 1H NMR (CDCl3) δ 2.33–2.41
(m, 1H), 3.15–3.23 (m, 1H), 3.81–4.18 (m, 4H), 7.15–7.66 (m,
10H). 19F NMR (CDCl3) δ Ϫ131.8 (dd, J = 159.9, 14.1 Hz, 1F),
Ϫ135.7 (dd, J = 161.9, 15.2 Hz, 1F). MS m/z (relative intensity)
302 (Mϩ, 4.70), 252 (3.29), 207 (14.47), 149 (45.39), 105
(100.00), 77 (57.90). HRMS Calcd. for C18H16F2O2: 302.1118.
Found: 302.1128.
Compound 2f: liquid, IR (film) (cmϪ1): 2989, 2891, 1670,
1609, 1504, 1446, 1327, 1221, 1039. 1H NMR (CDCl3)
δ 1.56 (s, 3H), 2.11–2.19 (m, 1H), 2.91–2.98 (m, 1H),
3.93–4.08 (m, 4H), 7.23–7.39 (m, 5H). 19F NMR (CDCl3)
δ Ϫ133.6 (dd, J = 159.3, 17.2 Hz, 1 F), Ϫ135.9 (dd, J = 162.2,
14.9 Hz, 1 F). MS m/z (relative intensity) 240 (Mϩ, 0.84), 225
(1.58), 190 (0.50), 175 (7.83), 133 (12.14), 87 (89.56), 43
1
Compound 2n: liquid. H NMR (CDCl3) δ 2.28–2.36 (m,
1H), 3.57–3.64 (m, 1H), 3.78–4.16 (m, 4H), 7.07–7.70 (m, 9H).
19F NMR (CDCl3) δ Ϫ131.9 (dd, J = 160.7, 13.8 Hz, 1F),
Ϫ135.3 (dd, J = 158.9, 13.5 Hz, 1F). MS m/z (relative
intensity) 336 (Mϩ, 5.18), 317 (0.53), 287 (16.09), 242 (11.29),
214 (40.56), 149 (100.00), 105 (94.22), 77 (35.81). Anal. Calcd
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 1 5 1 – 1 1 5 6
1154

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for C18H15ClF2O2: C, 64.20; H, 4.49; F, 11.28. Found: C, 64.50;
H, 4.11; F, 11.15%.
Compound 4e: liquid, 1H NMR (CDCl3) δ 6.39 (m, 1H), 7.19
(d, J = 0.6 Hz, 1H), 7.24 (m, 1H), 7.57–7.60 (m, 2H), 7.70–7.73
Compound 2o: liquid, IR (film) (cmϪ1): 2896, 1686, 1621,
1486, 1413, 1327, 1168, 1127, 1069. 1H NMR (CDCl3)
δ 2.28–2.36 (m, 1 H), 3.11–3.19 (m, 1 H), 3.76–4.12 (m, 4 H),
7.18–7.61 (m, 9 H). 19F NMR (CDCl3) δ Ϫ62.6 (s, 3F), Ϫ131.7
(dd, J = 159.3, 16.1 Hz, 1F), Ϫ135.2 (dd, J = 159.3, 13.8 Hz,
1F). MS m/z (relative intensity) 370 (Mϩ, 10.73), 320 (25.20),
248 (30.46), 149 (90.49), 105 (100.00), 77 (63.03). Anal. Calcd
for C19H15F5O2: C, 61.62; H, 4.08. Found: C, 62.81; H, 3.75%.
Compound 2p: liquid, IR (film) (cmϪ1): 3030, 2895, 1608,
1504, 1469, 1446, 1328, 1275, 1168, 1074, 1011. 1H NMR
(CDCl3) δ 2.33 (s, 3H), 2.33–2.41 (m, 1H), 3.14–3.21 (m, 1H),
3.82–4.14 (m, 4H), 7.16–7.32 (m, 7H), 7.43–7.46 (m, 2H). 19F
NMR (CDCl3) δ Ϫ132.2 (dd, J = 159.9, 14.4 Hz, 1F), Ϫ135.3
(dd, J = 159.3, 14.4 Hz, 1F). Anal. Calcd for C19H18F2O2: C,
72.14; H, 5.74; F, 12.01. Found: C, 72.35; H, 5.70; F, 12.26%.
Compound 2q: white solid, mp 111–112 ЊC. IR (film) (cmϪ1):
3024, 2964, 1612, 1584, 1511, 1467, 1302, 1276, 1255, 1168,
1175, 1076, 1014. 1H NMR (CDCl3) δ 2.37 (dddd, J = 14.4, 8.4,
0.6 Hz, 1H), 3.14 (dd, J = 14.1, 9.0 Hz, 1H), 3.82 (s, 3H), 3.85–
4.14 (m, 4H), 6.88–6.92 (m, 2H), 7.16–7.32 (m, 5H), 7.46–7.50
(m, 2H). 19F NMR (CDCl3) δ Ϫ132.2 (dd, J = 158.2, 14.7 Hz,
1F), Ϫ135.3 (dd, J = 158.2, 14.7 Hz, 1F). MS m/z (relative
intensity) 332 (Mϩ, 0.59), 301 (2.38), 252 (0.58), 237 (2.72), 221
(0.98), 192 (100.00), 179 (78.48), 135 (62.57), 107 (6.53), 77
(13.35). Anal. Calcd for C19H18F2O3: C, 68.67; H, 5.46; F, 11.43.
Found: C, 68.57; H, 5.39; F, 11.36%.
(m, 2H). 19F NMR (CDCl3) δ Ϫ161.8 (d, J = 4.2 Hz).
1
Compound 3e: liquid, IR (film) (cmϪ1): H NMR (CDCl3)
δ 2.97–3.06 (m, 1H), 3.63–3.69 (m, 1H), 7.37–7.40 (m, 2H),
7.62–7.69 (m, 2H), 9.55 (m, 1H). 19F NMR (CDCl3) δ Ϫ166.
MS m/z (relative intensity) 250 (Mϩ, 0.51), 231 (4.04), 221
(100.00), 201 (83.71), 181 (12.22), 151 (68.41), 131 (73.80), 69
(3.01). Anal. Calcd for C11H7F5O: C, 52.81; H, 2.82. Found: C,
53.31; H, 3.57%.
Compound 4f: liquid, IR (film) (cmϪ1): 2924, 1683, 1635,
1607, 1520, 1436, 1410, 1327, 1266, 1228, 1185, 1089. 1H NMR
(CDCl3) δ 2.31 (s, 3H), 6.03–6.05 (m, 1H), 7.18–7.25 (m, 1H),
7.35–7.40 (m, 2H), 7.62–7.66 (m, 2H). 19F NMR (CDCl3)
δ Ϫ162.8 (s, 1F). MS m/z (relative intensity) 176 (Mϩ, 100.00),
147 (15.30), 133 (40.55), 105 (24.20), 77 (29.77). HRMS Calcd
for C11H9FO: 176.0637; Found: 176.0654.
Compound 4g: liquid, 1H NMR (CDCl3) δ 2.31 (s, 3H), 6.04–
6.05 (m, 1H), 7.33–7.37 (m, 2H), 7.55–7.59 (m, 2H). 19F NMR
(CDCl3) δ Ϫ162.3 (s, 1F).
Compound 3g: liquid, IR (cmϪ1): 1716, 1500, 1453, 1402,
1362, 1331, 1286, 1221, 1181, 1155, 1092, 1016. 1H NMR (300
MHz, CDCl3): δ 2.40 (s, 3H), 2.95–3.02 (m, 1H), 3.52–3.60 (m,
1H), 7.15–7.18 (m, 2H), 7.30–7.34 (m, 2H). MS m/z (relative
intensity) 230 (Mϩ, 0.91), 210 (4.51), 187 (79.13), 167 (57.40),
151 (27.80), 111 (2.76), 43 (100.00). Anal. Calcd for
C11H9ClF2O: C, 57.28; H, 3.93; F, 16.47. Found: C, 57.32; H,
4.03; F, 16.74%.
Compound 4h: liquid. IR (cmϪ1): 3003, 2957, 1646, 1611,
1583, 1570, 1511, 1463, 1442, 1410, 1303, 1255, 1180, 1145,
1040. 1H NMR (300 MHz, CDCl3): δ 2.29 (s, 3H), 3.82 (s, 3H),
6.01 (s, 1H), 6.91–6.94 (m, 2H), 7.55–7.58 (m, 2H). 13C NMR
(500 MHz, CDCl3): δ 14.11, 55.11, 100.43, 114.01, 122.36,
124.20, 134.55, 148.52. MS m/z (relative intensity) 206, 191,
175, 163. HRMS Calcd for C12H11FO2: 206.0743. Found:
206.0714.
Hydrolysis of gem-difluorocyclopropyl derivatives 2 under acidic
conditions
A typical procedure: a 25 ml flask with a water condenser and a
magnetic stirring bar was charged with 2a (1.54 g, 6.8 mmol),
5 ml of saturated oxalic solution and 5 ml of dioxane, the
mixture was heated to 110 ЊC and stirred for 6 h. After
cooling to room temperature the content was extracted with
ether. The organic layer was dried over Na2SO4. After removal
of solvent under reduced pressure, the residue was purified
by flash chromatography on silica gel column. 3-Fluoro-2-
phenylfuran (4a) (0.23 g, 21%) was obtained as pale yellow
liquid.
Compound 4i: colorless liquid, IR (film) (cmϪ1): 2923, 1640,
1
1580, 1511, 1451, 1406, 1300, 1255, 1146. H NMR (CDCl3)
δ 2.32 (s, 3H), 2.37 (3, 3H), 6.04 (t, J = 1.2 Hz, 1H), 7.21 (d,
J = 7.8 Hz, 2H), 7.54–7.57 (m, 2H). 19F NMR (CDCl3) δ Ϫ163.9
(s, 1F). MS m/z (relative intensity) 190 (Mϩ, 100.00), 189
(47.53), 175 (8.55), 147 (38.82), 91 (17.65). Anal. Calcd for
C12H11FO: C, 75.77; H, 5.83; F, 9.99. Found C, 75.73; H, 5.82;
F, 10.09%.
Compound 4a: liquid, IR (film) (cmϪ1): 3059, 1633, 1602,
1
1510, 1490, 1433, 1281, 1267, 1113, 1066. H NMR (CDCl3)
δ 6.40–6.41 (m, 1H), 7.21–7.27 (m, 2H), 7.37–7.43 (m, 2 H),
7.67–7.70 (m, 2H). 19F NMR (CDCl3) δ Ϫ165.3 (s, 1F). MS m/z
(relative intensity) 162 (Mϩ, 6.62), 133 (11.83), 121 (6.75), 105
(100.00), 77 (93.15). Anal. Calcd for C10H7FO: C, 74.07; H,
4.35; F, 11.72. Found: C, 73.90; H, 4.24; F, 11.43%.
Compound 3j: yellow liquid, IR (film) (cmϪ1): 3017, 1718,
1623, 1526, 1456, 1411, 1364, 1328, 1287, 1224, 1168, 1128,
1071, 1018. 1H NMR (CDCl3) δ 2.43 (s, 3H), 3.03–3.11 (m, 1H),
3.61–3.69 (m, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 8.1 Hz,
2H). 19F NMR (CDCl3) δ Ϫ32.5–Ϫ132.4 (m, 2F), Ϫ62.7 (s, 3F).
MS m/z (relative intensity) 265 (Mϩ ϩ 1, 0.56), 245 (0.46), 221
(3.19), 201 (7.71), 195 (1.08), 151 (6.98), 43 (100.00). Anal.
Calcd for C12H9F5O: C, 54.56; H, 3.43; F, 35.96. Found: C,
54.25; H, 3.28; F, 35.80%.
Compound 4b: liquid, IR (film) (cmϪ1): 1631, 1568, 1507,
1
1486, 1435, 1400, 1278, 1265, 1168, 1086. H NMR (CDCl3)
δ 6.42–6.43 (m, 1H), 7.23–7.26 (m, 1H), 7.36–7.39 (m, 2 H),
7.58–7.62 (m, 2H). 19F NMR (CDCl3) δ Ϫ164.4 (s, 1F). MS m/z
(relative intensity) 196 (Mϩ, 100.00), 167 (31.74), 161 (2.09), 133
(52.59), 77 (93.15). Anal. Calcd for C10H6ClFO: C, 61.09; H,
3.08; F, 9.66. Found: C, 61.14; H, 2.94; F, 9.47%.
Compound 4k, white solid, mp 70–71 ЊC. IR (film) (cmϪ1):
2965, 1633, 1574, 1507, 1412, 1247, 1179, 1041. 1H NMR
(CDCl3) δ 3.85 (s, 3H), 6.64 (d, J = 0.9 Hz, 1H), 6.90–7.00 (m,
2H), 7.25–7.43 (m, 3H), 7.67–7.71 (m, 4H). 19F NMR (CDCl3)
δ Ϫ164.2 (s, 1F). MS m/z (relative intensity) 268 (Mϩ, 100.00),
253 (85.33), 225 (29.78), 196 (6.43), 176 (8.15), 77 (9.64). Anal.
Calcd for C17H13FO2: C, 76.11; H, 4.88; F, 7.08. Found: C,
76.12; H, 4.88; F, 6.99%. X-Ray crystallographic data:† C17H13-
FO2, Mr = 268.27; crystal system, monoclinic; space group,
P2(1)/c; unit cell dimensions, a = 3.9188 (8) Å, b = 30.250 (6) Å,
c = 11.013 (2) Å, α = 90Њ, β = 100.187 (4)Њ, γ = 90Њ; V = 1284.9 (5)
Å3; Z = 4; Dx = 1.387 g cmϪ3; λ(Mo-Kα) = 0.7153 Å; µ = 1.00
cmϪ1; F(000) = 560; T = 293 (2) K; GoF = 0.823; Rint = 0.0775;
Compound 4c: liquid, IR (film) (cmϪ1): 2960, 2839, 1639,
1608, 1575, 1520, 1496, 1437, 1301, 1252, 1118, 1087, 1037. 1H
NMR (CDCl3) δ 3.82 (s, 3H), 6.39–6.40 (m, 1H), 6.93–6.96 (m,
2H), 7.18–7.20 (m, 1H), 7.60–7.63 (m, 2H). 19F NMR (CDCl3)
δ Ϫ168.0 (s, 1F). MS m/z (relative intensity) 192 (Mϩ, 100.00),
177 (10.83), 151 (46.75), 107 (13.15). HRMS Calcd for
C11H9FO2: 192.0587; Found: 192.0590.
Compound 4d: liquid, IR (film) (cmϪ1): 2924, 1683, 1635,
1607, 1520, 1436, 1410, 1327, 1266, 1228, 1185, 1089. 1H NMR
(CDCl3) δ 2.36 (s, 3H), 6.40–6.41 (m, 1H), 7.20–7.23 (m, 3H),
7.58 (d, J = 8.1 Hz, 2H). 19F NMR (CDCl3) δ Ϫ166.0 (s, 1F).
MS m/z (relative intensity) 176 (Mϩ, 100.00), 147 (35.31), 133
(29.21). Anal. Calcd for C11H9FO: C, 74.99; H, 5.15; F, 10.78.
Found: C, 74.78; H, 4.94; F, 10.74%.
† CCDC reference numbers 200171. See http://www.rsc.org/suppdata/
ob/b2/b212232d/ for crystallographic data in .cif or other electronic
format.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 1 5 1 – 1 1 5 6
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wR(F 2) = 0.0803 for 7845 reflections and 234 parameters and
R(F) = 0.0425.†
(9.91), 105 (7.40), 77 (16.51). HRMS. Calcd for C17H13FO2:
268.0900. Found: 268.0930.
Compound 4l: solid, mp 88–89 ЊC. IR (film) (cmϪ1): 2921,
1631, 1596, 1508, 1483, 1451, 1429, 1406, 1317, 1261, 1149,
1110. 1H NMR (CDCl3) δ 2.31 (s, 3H), 6.59 (d, J = 0.9 Hz, 1H),
7.16–7.25 (m, 3H), 7.31–7.36 (m, 2H), 7.60–7.64 (m, 3H). 19F
NMR (CDCl3) δ Ϫ162.4 (s, 1F). MS m/z (relative intensity)
252 (Mϩ, 100.00), 237 (1.87), 223 (3.84), 209 (11.17), 191 (5.16),
175 (0.57), 147 (7.34), 133 (8.05), 77 (2.89). HRMS. Calcd
for C17H13FO: 252.0950. Found: 252.0972. Anal. Calcd for
C17H14F2O: C, 80.93; H, 5.19. Found: C, 80.77; H, 5.32%.
Compound 3l: solid, mp 92–93 ЊC. IR (film) (cmϪ1): 3030,
2927, 1679, 1597, 1521, 1450, 1407, 1326, 1286, 1226, 1164,
1043. 1H NMR (CDCl3) δ 2.35 (s, 3H), 3.58–3.65 (m, 1H), 3.79–
3.85 (m, 1H), 7.16–7.23 (m, 2H), 7.51–7.67 (m, 3H), 8.03–8.06
(m, 2H). 19F NMR (CDCl3) δ Ϫ132.2 (m, 2F). MS m/z (relative
intensity) 272 (Mϩ, 0.87), 252 (0.66), 225 (29.78), 167 (6.29), 105
(100.00), 91 (2.61), 77 (25.94). Anal. Calcd for C17H14F2O: C,
74.99; H, 5.18; F, 13.95. Found: C, 74.88; H, 5.15; F, 13.70%.
Compound 3q: solid, mp 79–80 ЊC. IR (film) (cmϪ1): 3030,
1668, 1601, 1573, 1511, 1459, 1452, 1318, 1291, 1260, 1172,
1
1028. H NMR (CDCl3) δ 3.56–3.62 (m, 1H), 3.80–3.85 (m,
1H), 3.90 (s, 3H), 6.99–7.01 (m, 2H), 7.31–7.39 (m, 4H), 8.02–
8.05 (m, 2H). 19F NMR (CDCl3) δ Ϫ132.4–Ϫ132.3 (m, 2F). MS
m/z (relative intensity) 288 (Mϩ, 7.44), 257 (0.28), 221 (0.82),
182 (6.31), 167 (2.56), 135 (100.00), 107 (7.63), 77 (19.12). Anal.
Calcd for C17H14F2O2: C, 70.83; H, 4.89; F, 13.18. Found: C,
70.81; H, 4.93; F, 13.02%.
Acknowledgement
We thank Professor H. M. Wu for instructive advice on
structure determination and Natural Science Foundation of
China (D20032010) for support of this work.
1
Compound 3m: solid, mp 60–61 ЊC. IR (film) (cmϪ1):. H
References
NMR (CDCl3) δ 3.61–3.69 (m, 1H), 3.82–3.91 (m, 1H), 7.29–
7.67 (m, 8H), 8.03–8.07 (m, 2H). 19F NMR (CDCl3) δ Ϫ132.6
(d, J = 5.1 Hz, 2F). MS m/z (relative intensity) 258 (Mϩ, 0.71),
238 (0.63), 209 (0.76), 105 (100.00), 77 (40.33). HRMS. Calcd
for C16H12F2O: 258.0856. Found: 258.0877.
1 (a) Chemistry of Organic Fluorine Compounds II, ed. M. Hudlický
and A. E. Pavlath, American Chemical Society, Washington, DC,
1995; (b) D. L. S. Brahams and W. P. Dailey, Chem. Rev., 1996, 96,
1585–1632; (c) M. R. C. Gerstenberger and A. Haas, Angew. Chem.,
Int. Ed. Engl., 1981, 20, 647–667; (d ) M. J. Tozer and T. F. Herpin,
Tetrahedron, 1996, 26, 8619–8683.
2 (a) V. P. Erbes and W. Boland, Helv. Chim. Acta, 1992, 75, 766–772;
(b) A. Medaghri-alaoui, H. Choukroun, P. Calas, C. Amatore and
A. Commeyras, J. Fluorine Chem., 1991, 1–3, 71.
Compound 3n: mp 84–85 ЊC. IR (film) (cmϪ1): 3030, 1680,
1596, 1498, 1449, 1400, 1324, 1289, 1226, 1116, 1097, 1053,
1
1017. H NMR (CDCl3) δ 3.57–3.65 (m, 1H), 3.79–3.86 (m,
3 C. Beard and N. H. Fried, Tetrahedron Lett., 1966, 22, 3281.
4 (a) Y. Kobayashi, T. Taguchi, M. Mamada, H. Shimizu and
H. Murohashi, Chem. Pharm. Bull., 1979, 27, 3123; (b) Y.
Kobayashi, T. Taguchi, T. Morikawa, T. Takase and H. Takanashi,
Tetrahedron Lett., 1980, 21, 1047; (c) Y. Kobayashi, T. Taguchi,
T. Terada, J. Oshida, M. Morisaki and N. Ikekawa, Tetrahedron
Lett., 1979, 20, 2023; (d ) Y. Kobayashi, T. Morikawa, A. Yoshizawa
and T. Taguchi, Tetrahedron Lett., 1981, 22, 5297; (e) Y. Kobayashi,
T. Taguchi, T. Morikawa, T. Takase and H. Takanashi, J. Org.
Chem., 1982, 47, 3232.
5 F. Tian, V. K. Kruger, O. Bautista, J.-X. Duan, A.-R. Li,
W. R. Dolbier Jr. and Q.-Y. Chen, Org. Lett., 2000, 2, 563–564.
6 T. Itoh, N. Ishida, K. Mitsukura and K. Uneyama, J. Fluorine
Chem., 2001, 112, 63–68.
7 W. Xu and Q.-Y. Chen, J. Org. Chem., 2002, 67, 9421–9427.
8 (a) R. B. Woodward, F. E. Bader, H. Bickel, A. J. Frey and
R. W. Kierstead, J. Org. Chem., 1958, 2, 1; (b) H. B. Henbest,
W. R. Jackson and I. Malunowicz, J. Chem. Soc. (C), 1967, 2469;
(c) I. Salazar and E. Dfaz, Tetrahedron, 1979, 815–818.
9 O. G. Kulinkovic, I. G. Tishchenko and N. A. Roslik, J. Org. Chem.
(USSR), 1984, 480–484.
1H), 7.24–7.28 (m, 2H), 7.32–7.36 (m, 2H), 7.51–7.57 (m, 4H),
8.03–8.06 (m, 1H). 19F NMR (CDCl3) δ Ϫ131.8 (t, J = 6.9 Hz,
2F). MS m/z (relative intensity) 292 (Mϩ, 1.54), 272 (0.58), 187
(1.11), 167 (3.60), 151 (9.33), 105 (100.00), 77 (39.30). Anal.
Calcd for C16H11ClF2O: C, 65.65; H, 3.79; F, 12.98. Found: C,
65.51; H, 3.84; F, 13.24%.
Compound 3o: solid, mp 61–62 ЊC. IR (film) (cmϪ1): 1687,
1
1621, 1452, 1329, 1169, 1069, 1137. H NMR (CDCl3) δ 3.67–
3.72 (m, 1H), 3.89–4.92 (m, 1H), 7.44–7.69 (m, 7H), 8.04–8.07
(m, 2H). 19F NMR (CDCl3) δ Ϫ62.6 (s, 3 F), Ϫ132.0 (m, 2F).
MS m/z (relative intensity) 326 (Mϩ, 1.52), 307 (1.24), 221
(1.07), 208 (6.50), 151 (13.29), 105 (100.00), 77 (42.49), 69
(1.22). Anal. Calcd for C17H11F5O: C, 62.58; H, 3.40; F, 29.11.
Found: C, 61.91; H, 3.34; F, 29.44%.
Compound 4p: solid, mp 60–61 ЊC. IR (film) (cmϪ1): 2920,
1632, 1598, 1501, 1428, 1318, 1150, 1043, 1009. 1H NMR
(CDCl3) δ 2.38 (s, 3H), 6.61 (d, J = 1.2 Hz, 1H), 7.20–7.28 (m,
3H), 7.40–7.45 (m, 2H), 7.74–7.77 (m, 2H). 19F NMR (CDCl3)
δ Ϫ161.4 (s, 1F). MS m/z (relative intensity) 252 (Mϩ, 100.00),
237 (1.72), 223 (1.72), 209 (12.74), 147 (9.43), 77 (7.57). HRMS.
Calcd for C17H13FO: 252.0950. Found: 252.0978.
10 (a) W. R. Dolbier Jr., Acc. Chem. Res., 1981, 14, 195; (b) S. J. Getty,
D. A. Hrovat and W. T. Borden, J. Am. Chem. Soc., 1994, 116, 1521.
11 (a) E. Brenna, N. Caraccia, C. Fuganyi, D. Fuganti and P. Grasselli,
Tetrahedron. Asymmetry, 1997, 3801–3805; (b) H.-J. Kno˝lker,
B. Ahrens, P. Gonser, M. Heininger and G. Jones, Tetrahedron, 2000,
2259–2271; (c) V. Shadakshari and S. K. Nayak, Tetrahedron, 2001,
8185–8188.
Compound 3p: white solid, mp 98–99 ЊC. IR (film) (cmϪ1):
3045, 1673, 1607, 1506, 1462, 1436, 1333, 1285, 1231, 1185,
1
1170, 1048, 1000. H NMR (CDCl3) δ 2.45 (s, 3H), 3.59–3.66
12 P. A. Jacobi, J. I. Kravitz and W. J. Zheng, J. Org. Chem., 1995, 376.
13 1,3-Dioxan-2-ylmethyltriphenylphosphonium bromide was pre-
pared as follows: a mixture of (80 g, 479 mmol) and triphenyl-
phosphine (125 g, 476 mmol) in anhydrous acetonitrile (250 ml) was
heated to reflux for 24 h. The solvent was removed and the residue
was dissolved in dichloromethane (100 ml) and diluted with ether.
The precipitated solid was collected by filtration, washed with dry
ether and dried under vacuum to give the salt (164 g, 80% yield).
14 M. Kuse and M. Isobe, Tetrahedron, 2000, 2629–2639.
15 H. J. Dauben Jr., B. Löken and H. J. Ringold, J. Am. Chem. Soc.,
1954, 1359–1362.
(m, 1H), 3.80–3.89 (m, 1H), 7.29–7.39 (m, 7H), 7.94–7.96 (m,
2H). 19F NMR (CDCl3) δ Ϫ132.3–Ϫ132.2 (m, 2F). MS m/z
(relative intensity) 272 (Mϩ, 2.87), 257 (1.29), 237 (0.54), 222
(0.30), 151 (6.84), 119 (100.00), 91 (27.36), 77 (3.06). Anal.
Calcd for C17H14F2O: C, 74.99; H, 5.18; F, 13.95. Found: C,
74.94; H, 5.10; F, 13.79%.
Compound 4q: solid, mp 66–67 ЊC. IR (film) (cmϪ1): 2961,
1
1630, 1583, 1501, 1431, 1305, 1253, 1046. H NMR (CDCl3)
δ 3.86 (s, 3H), 6.54 (d, J = 0.6 Hz, 1H), 6.94–6.97 (m, 2H), 7.25–
7.27 (m, 1H), 7.40–7.45 (m, 2H), 7.62–7.76 (m, 4H). 19F NMR
(CDCl3) δ Ϫ161.4 (s, 1F). MS m/z (relative intensity) 268 (Mϩ,
100.00), 253 (66.00), 225 (13.34), 196 (9.86), 176 (5.36), 134
16 J. R. Dimmock and L. M. Smith, J. Pharm. Sci., 1980, 575–580.
17 B. B. Lohray, T. H. Kalantar, B. M. Kim, C. Y. Park and T. Shibata,
Tetrahedron Lett., 1989, 2041–2044.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 1 5 1 – 1 1 5 6
1156