Chemistry of difluorocarbene: Synthesis and conversion of difluoro(methylene)cyclopropanes

Article abstract of DOI:10.1002/ejoc.200600616

Difluoro(methylene)cyclopropanes (F₂MCPs) were prepared directly by difluorocarbene addition to allenes, and the resulting F₂MCPs were converted into a variety of difluoro(methylene)cyclopropane derivatives through Heck reactions and

Full text of DOI:10.1002/ejoc.200600616

FULL PAPER
DOI: 10.1002/ejoc.200600616
Chemistry of Difluorocarbene: Synthesis and Conversion of
Difluoro(methylene)cyclopropanes
Zhan-Ling Cheng,[a] Ji-Chang Xiao,[a] Chao Liu,[a] and Qing-Yun Chen*[a]
Keywords: Difluorocarbene / Cyclopropanes / Allenes
Difluoro(methylene)cyclopropanes (F2MCPs) were prepared
directly by difluorocarbene addition to allenes, and the re-
sulting F2MCPs were converted into a variety of difluoro(me-
thylene)cyclopropane derivatives through Heck reactions
and electrophilic substitutions. The ring-opening reactions of
F2MCPs with I2 are reported and a plausible reaction mecha-
nism is also discussed.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
Introduction
Methylenecyclopropane derivatives (MCPs) have been
well documented as useful synthetic intermediates in or-
ganic chemistry over the last decade (Scheme 1),[1] while the
methylenecyclopropane moiety is also found in biologically
active natural substances such as MCPG and its metabolite
MCPF-CoA.[2] These compounds’ biological activities have
also attracted considerable attention.[3] The introduction of
fluorine onto the rings of such methylenecyclopropanes
should have profound effects on their biological activities
and chemical reactivities, due to the strongly electron-with-
drawing effect of fluorine, but the synthesis of these fluori-
Scheme 1. Structures of various methylenecyclopropanes.
nated analogues
–
difluoro(methylene)cyclopropanes
(F2MCPs) – is rather difficult. Taguchi has developed two
efficient methods for the synthesis of F2MCPs[4] – one
through the elimination reaction of the selenoxide-derived
(difluorocyclopropyl)methanols and the other through the
cyclopropyl anion-promoted β-elimination reaction of
silylated difluorocyclopropanes – but multiple reaction
steps are needed for both methods. The development of new
methods to produce these compounds is therefore of cur-
rent interest.
Difluorocyclopropane derivatives are usually prepared
by difluorocarbene addition to alkenes.[5] A variety of di-
fluorocarbene precursors have been developed, but these
precursors are either inefficient or difficult to obtain:[5b] di-
fluorodiazirine, Me3SnCF3 and PhHgCF3, for example, re-
quire several steps to prepare and involve expensive and/or
toxic materials. Hexafluoropropylene oxide (HFPO) is also
limited by its availability and its reactions must be carried
out in an autoclave, while the most common precursor,
ClCF2CO2Na, is hygroscopic and requires harsh reaction
conditions to ensure good yields of products. Recently,
though,
trimethylsilyl
fluorosulfonyldifluoroacetate
(FO2SCF2CO2SiMe3, TFDA), which can be easily prepared
from considerably less expensive materials, has been re-
ported to be a highly versatile source of difluorocarbene.[6]
Dolbier and our group found that difluorocarbene gener-
ated from TFDA can add efficiently and effectively to a
variety of alkynes and alkenes under mild conditions.[7]
Difluoro(methylene)cyclopropane backbones might be
directly accessible by difluorocarbene addition to allenic
compounds or their equivalents,[8] and several attempts to
explore this possibility have been made.[9] Dolbier found
that a mixture of regioisomers and double cyclopropan-
ation products was formed from the reaction between di-
fluorocarbene and simple allene when PhHgCF3 was used
as the difluorocarbene source,[9b] while Bargar prepared
bioactive F2MCPs in low yield by treatment of alkyl allenes
with difluorocarbene derived from the decomposition of
ClCF2CO2Na, accompanied by the formation of double cy-
clopropanation products.[9c]
[a] Key Laboratory of Organofluorine Chemistry, Shanghai Insti-
tute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, 200032 Shanghai, China
As an extension of our studies on difluorocarbene chem-
istry and our interest in F2MCP chemistry, we wish to re-
E-mail: Chenqy@mail.sioc.ac.cn
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Z.-L. Cheng, J.-C. Xiao, C. Liu, Q.-Y. Chen
FULL PAPER
port an improved synthesis of F2MCPs from TFDA and Table 2. Difluorocarbene addition to sulfonyl allenes.[a]
allenic compounds and describe the chemical conversions
of F2MCPs.
Results and Discussion
Entry
1
R1
R2
2
Conversion (%) Yield (%)[b]
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
Me
H
H
Et
tBu
–(CH2)5–
Ph Me
Me
H
Me
Me
Me
2a
2b
2c
2d
2e
2f
63
0
0
57
57
56
60
63
0
0
80
83
88
60
Synthesis of Difluoro(methylene)cyclopropanes
The addition of difluorocarbene to allenes was initially
investigated by treatment of phenylpropadiene with TFDA
in the presence of NaF in diglyme (DG) at 120 °C. Unfortu-
nately, a mixture of rearranged product, starting material
and double cyclopropanation product was formed. It had
been reported that the introduction of a sulfonyl group into
an allene could improve the regioselectivity in its cycload-
dition reaction,[10] so sulfonyl allenes were then chosen as
the substrates. Treatment of 1a with TFDA under condi-
tions similar to those described above did give the difluoro-
(methylene)cyclopropane product 2a in 22% yield, with the
amount of TFDA not significantly affecting the yield of 2a
produced (Table 1, Entries 1 and 2). An improvement was
achieved when toluene or xylene was used as the solvent
(Table 1, Entries 3 and 4).
1g
2g
[a] Reactions were carried out with 1/TFDA/NaF 1:2:0.1 over 3 h.
[b] Isolated yields based on the conversion of 1.
Table 1. Conditions for and results of difluorocarbene addition to
allenes.
Figure 1. X-ray crystallography for 2f. Selected bond lengths [Å],
bond angles [°] and torsion angles [°]: S(1)–O(1) 1.4251(14), S(1)–
C(1) 1.737(2), C(1)–C(2) 1.303(3), C(2)–C(3) 1.446(3), C(1)–H(1)
0.88(2), C(2)–C(4) 1.476(2), C(3)–C(4) 1.491(3); C(1)–C(2)–C(3)
149.30(19), C(3)–C(2)–C(4) 61.35(13), C(2)–C(3)–C(4) 60.34(12);
O(1)–S(1)–C(1)–C(2) –3.1(2), S(1)–C(1)–C(2)–C(3) –179.0(3), S(1)–
C(1)–C(2)–C(4) –3.8(5), C(1)–C(2)–C(3)–C(4) 177.2(4), C(1)–C(2)–
C(4)–C(9) –69.9(4), C(3)–C(2)–C(4)–C(9) 107.29(19), C(1)–C(2)–
C(4)–C(5) 74.9(4).
Entry Solvent TFDA (equiv.) Temp. (°C)[a] Yield (%)[b]
1
2
3
4
DG
DG
toluene
xylene
1.5
3
2
120
120
(reflux)
120
22
20
39
40
2
While MCPs have been applied in a wide variety of syn-
thetic transformations, F2MCPs have so far been less well
explored, due to their poor accessibility. With the above di-
fluoro(methylene)cyclopropane derivatives to hand, we next
investigated their conversion into diversely functionalized
derivatives.
[a] External temperature. [b] Isolated yields. They are based on 1a
used.
A series of sulfonyl allenes were then subjected to the
optimal reaction conditions described above. In most cases,
a wide range of F2MCPs were obtained in good yield by
this methodology. The substituents on the double bond in-
fluenced the reactivity significantly: regioselective difluo-
rocarbene addition proceeded smoothly with the allenes
Heck Reactions between F2MCP and Aryl Iodides
Initial investigations into Heck reactions were made with
possessing geminal dialkyl substituents (1a and 1d–1g), F2MCP 2a and p-iodoanisole as the substrates. Of the cata-
while the unsubstituted allene 1b and the monosubstituted lysts, bases, solvents and temperatures screened, the combi-
allene 1c did not give the corresponding F2MCPs. (Table 2, nation of Pd(PPh3)4 and Ag2CO3 in DMF at 120 °C pro-
Entries 2 and 3), with the starting materials 1b and 1c being duced the best results for this transformation, with the cor-
recovered; this is probably because of the relatively low elec- responding coupling product 4aa being obtained in 74%
tron density in the double bond. The structure of 2f was yield (Table 3). For comparison, no ring-opening products
further confirmed by single-crystal X-ray diffraction analy- were detected with their nonfluorinated analogues, despite
sis (Figure 1).
the high conformational strain of 2a.[11]
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Synthesis and Conversion of Difluoro(methylene)cyclopropanes
Table 3. Conditions and results of Heck reactions.[a]
FULL PAPER
Entry
Catalyst
Base
Solvent
Temp.(°C)
Yield (%)[b]
1
2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)4
Pd(OAc)2
PdCl2(PPh3)2
Pd(PPh3)4
Ag2CO3
Ag2CO3
NaHCO3
Ag2CO3/K2CO3
Ag2O
CH3CN
DMF
DMF
DMF
DMF
DMF
DMF
room temp.
0
50
0
120
120
80
120
120
120
3
4[c]
5
0
43
18
74
6
7
Ag2CO3
Ag2CO3
[a] Reactions were carried out in the presence of palladium catalyst (10 mol%). [b] Isolated yields. [c] The ratio of Ag2CO3 and K2CO3
is 0.05:4.
We then studied the scope of the reaction by allowing erate to good yields. The presence of a bulky group such as
the F2MCPs 2 to react with a variety of aryl iodides 3 under tert-butyl on the cyclopropane ring had no effect on the
the optimal reaction conditions described above; the results yield of 4 (Table 4, Entry 8).
are summarized in Table 4. No desired product was ob-
tained in the case of F2MCP 2g (Table 4, Entry 10), which
Reactions between F2MCPs and Electrophiles
might be a result of the presence of the phenyl group at the
allylic position. Neither was any corresponding product was
formed in the case of 1-iodo-4-nitrobenzene (3f), which
contains a strongly electron-withdrawing group on the ben-
zene ring, (Table 4, Entry 6). In other cases the reactions
proceeded smoothly to give the arylated F2MCPs 4 in mod-
Since the presence of a sulfone group can stabilize the
adjacent carbon anion, vinyllithium intermediates gener-
ated by direct lithiation of vinyl sulfones have been used
in many practical organic syntheses.[12] Application of this
method to F2MCPs 2 was also successful; the results are
given in Table 5. Treatment of F2MCP 2a with nBuLi in
THF at –78 °C converted 2a into the lithiated intermediate
I, while subsequent treatment (after workup) with benzalde-
hyde resulted in the formation of 5a in 75% yield (Table 5,
Entry 1).
Table 4. Heck reactions between of F2MCPs 2 and aryl iodides.[a]
Similarly to the situation in the Heck reactions, none of
the desired product was obtained when 2g, containing a
phenyl substituent on the cyclopropane ring, was used as
the starting material (Table 5, Entry 5), but all the other
F2MCPs gave modest to good yields of the desired prod-
ucts. The matter of whether aromatic aldehydes or aliphatic
aldehydes were being used had some effect on the yield of
5: decreased yields of 5 were obtained when aliphatic alde-
hydes such as propanal were used, for example (Table 5,
Entry 6). As well as aldehydes, other electrophiles such as
methyl iodide and iodine were also applicable in this con-
version (Table 5, Entries 7 and 8). It should be noted that
the iodinated product 5h, an iodoalkene derivative, might
be suitable for further transformations.
Entry
2
ArI
4
Yield (%)[b]
1
2
3
4
5
6
7
8
9
2a
2a
2a
2a
2a
2a
2d
2e
2f
3a
3b
3c
3d
3e
3f
3a
3a
3a
3a
4aa
4ab
4ac
4ad
4ae
4af
4da
4ea
4fa
4ga
74
60
55
37
25
0
57
60
66
0
CuI-Catalyzed Ring-Opening Reactions between F2MCPs
and Iodine
There is a growing interest in ring-opening of MCPs: Hu-
ang and co-workers recently reported CuI/I2-catalyzed ring-
opening reactions of MCPs with I2,[13] whilst Shi’s group
10
2g
[a] 2/3/Pd(PPh3)4/Ag2CO3 = 1:1.1:0.1:4.0. [b] Isolated yields.
Eur. J. Org. Chem. 2006, 5581–5587
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Z.-L. Cheng, J.-C. Xiao, C. Liu, Q.-Y. Chen
FULL PAPER
Table 5. Reactions between 2 and electrophiles.[a]
Entry
2
Electrophile
5
Yield (%)[b]
1
2
3
4
5
6
7
8
2a
2d
2e
2f
2g
2a
2a
2a
PhCHO
PhCHO
PhCHO
PhCHO
PhCHO
nPrCHO
MeI
5a [E = CH(OH)Ph]
5b [E = CH(OH)Ph]
5c [E = CH(OH)Ph]
5d [E = CH(OH)Ph]
5e [E = CH(OH)Ph]
5f [E = CH(OH)nPr]
5g (E = Me)
75
55
70
61
0
37
60
57
I2
5h (E = I)
[a] Reactions were carried out with 2/E+ = 1:1.2. [b] Isolated yields.
found that this reaction can also occur in the absence of and CuI2 would first be established under the reaction con-
CuI.[14] In the next step of our research into F2MCPs, we ditions, while the oxidative addition of CuI2 to the distal
investigated their ring-opening reactions. It was found that C–C bond of F2MCPs would then result in the formation
the reaction between 2a and I2 in the presence of CuI read- of intermediate A, followed by reductive elimination to give
ily produced 6a in 93% yield (Table 6, Entry 1). Other B. The final product 6 would be formed after oxidative
F2MCPs were studied similarly, and the results are listed in cleavage by CuI2.
Table 6.
Table 6. Ring-opening reactions between 2 and I2.[a]
Entry
2
R1
R2
6
Yield (%)[b]
1
2
3
4
5
2a
2d
2e
2f
Me
Et
tBu
–(CH2)5–
Ph
Me
Me
Me
6a
6d
6e
6f
93
80
0
95
0
2g
Me
6g
[a] Reactions were carried out with 2/CuI/I2 = 1:0.05:3. [b] Isolated
yields.
As illustrated in Table 6, the reactions were significantly
affected by the substituents on the cyclopropane rings. No
reactions occurred, even with prolonged reaction times,
with F2MCPs bearing bulky or aromatic substituents on
their cyclopropane rings (Table 6, Entries 3 and 5), while
Scheme 2. Proposed mechanism for CuI-promoted ring-opening re-
actions of F2MCPs.
Conclusions
In summary, we have developed a convenient and ef-
with other F2MCPs the corresponding ring-opening prod- ficient method for the synthesis of difluoro(methylene)cy-
ucts were obtained in good to excellent yields. clopropanes by addition of difluorocarbene to allenes. Sub-
Ito has proposed a metallocyclic intermediate mecha- sequent Heck reactions or electrophilic reactions of the
nism to explain the selective distal or proximal C–C bond F2MCPs were investigated. The procedures described here
cleavage of MCPs through Pd- and Pt-catalysed silabor- should be adaptable to the synthesis of other difluoro(me-
ation,[15] while Huang has suggested a copper-containing thylene)cyclopropane derivatives. The ring-opening reac-
cyclic intermediate mechanism for CuX2-mediated ring- tions of F2MCPs were also studied, providing a novel route
opening reactions of MCPs.[13] In view of the similarity of to difluoromethylated derivatives. Other synthetically useful
MCPs and F2MCPs, a plausible mechanism for this reac- transformations of F2MCPs are under continuing investiga-
tion is shown in Scheme 2. An equilibrium between CuI tion in our laboratory.
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Synthesis and Conversion of Difluoro(methylene)cyclopropanes
FULL PAPER
MS (EI): m/z: 286 [M]+ (8.17), 65 (100). C14H16F2O2S (286.1): C
58.72, H 5.63; found: C 58.91, H 5.56.
Experimental Section
General: 1H NMR spectra were recorded on a Bruker AM 300
(300 MHz) spectrometer with TMS as an internal standard (nega-
tive for upfield). 19F NMR spectra were recorded on a Bruker
AM 300 (282 MHz) with CFCl3 as an external standard (negative
for upfield). The solvent for NMR measurement was CDCl3 or
CD3COCD3, which were purchased from Cambridge Isotope
Laboratories, Aldrich or Acros. MS and HRMS were recorded on
a Hewlett–Packard HP-5989A spectrometer and a Finnigan MAT-
8483 mass spectrometer. Elementary analyses were obtained on a
Perkin–Elmer 2400 Series II Elemental Analyzer. Infrared spectra
were measured with a Perkin–Elmer 983 spectrometer. TLC analy-
sis were performed on silica gel plates, column chromatography
over silica gel (mesh 300–400), both obtained from Qingdao Ocean
Chemicals. Diglyme, THF and CH3CN were purified by standard
methods. FSO2CF2COOSiMe3 (TFDA) and sulfonyl allenes were
prepared as described in the literature.[7,16] nBuLi and aryl iodides
were used as commercially available.
1-{[(2-tert-Butyl-3,3-difluoro-2-methylcyclopropylidene)methyl]-
sulfonyl}-4-methylbenzene (2e): Solid, yield 149 mg (83 %). 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 1.15 (s, 9 H), 1.40 (t, J =
2.1 Hz, 3 H), 2.46 (s, 3 H), 7.08 (s, 1 H), 7.38 (d, J = 8.4 Hz, 2 H),
7.80 (d, J = 8.7 Hz, 2 H) ppm. 19F NMR (282 MHz, CDCl3,
25 °C): δ = –131.6 (d, J = 188.1 Hz, 1 F), –140.0 (d, J = 188.1 Hz,
1 F) ppm. IR (film): ν = 2964, 2927, 1839, 1735, 1598, 1468, 1381,
˜
1325, 1239, 1153 cm–1. MS (EI): m/z: 315 [M + 1]+ (28.76), 139
(100). HRMS (MALDI) calcd. for C16H20F2O2SNa+: 337.1056;
found: 337.1044.
1-{[(2,2-Difluoro-3-methyl-3-phenylcyclopropylidene)methyl]-
sulfonyl}-4-methylbenzene (2g): Solid, yield 120 mg (60 %). 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 2.08 (t, J = 3.3 Hz, 3 H), 2.44
(s, 3 H), 4.17 (s, 1 H), 7.17 (d, J = 6.9 Hz, 2 H), 7.24–7.42 (m, 5
H), 7.79 (d, J = 8.1 Hz, 2 H) ppm. 19F NMR (282 MHz, CDCl3,
25 °C): δ = –122.3 (s, 2 F) ppm. IR (film): ν = 2971, 2918, 1641,
˜
1615, 1597, 1462, 1450, 1386, 1361, 1317, 1259, 1137 cm–1. MS
(EI): m/z: 334 [M]+ (1.19), 179 (100). C16H18F2O2S (312.1): C
64.65, H 4.82; found: C 64.70, H 4.96.
Typical Procedure for the Addition of Difluorocarbene to Allenes:
Compound 1f (273 mg, 1.04 mmol), NaF (4 mg, 10 mol%) and xy-
lene (2 mL) were placed under N2 in a Schlenk tube fitted with a
magnetic stirring bar and a pressure-equalizing dropping funnel.
The mixture was heated to 120 °C (oil bath), TFDA (530 mg,
2.0 equiv.) was added dropwise with stirring over a period of about
40 min, and the mixture was then stirred for another 2.5 h. at this
temperature. After having cooled to room temperature, the reaction
mixture was directly purified by flash chromatography on a silica
gel column. Compound 2f (161 mg, 88%) was obtained as a white
solid, while 1f (120 mg, conversion 56%) was recovered.
Typical Procedure for Heck Reactions between Compounds 2 and
Aryl Iodides: Compounds 2a (39 mg) and 3a (37 mg, 1.1 equiv.),
Ag2CO3 (170 mg, 4.0 equiv.) and DMF (3 mL) were placed under
N2 in a Schlenk tube containing a magnetic stirring bar. The mix-
ture was cooled to –78 °C with a dry ice/alcohol bath and degassed
three times. Pd(PPh3)4 (17 mg, 10 mol-%) was then added, and the
mixture was heated at 120 °C (oil bath) and stirred for 24 h. The
reaction mixture was allowed to cool to room temperature and fil-
tered, the solid was washed with ethyl acetate (10 mL), and the
combined filtrate was then washed with water and brine and dried
with MgSO4. After removal of solvent under reduced pressure, the
residue was purified by flash chromatography on a silica gel column
to provide 4aa (40 mg, 74%) as a white solid.
1,1-Difluoro-2-[(tolyl-4-sulfonyl)methylidene]spiro[2.5]octane (2f):
1
Solid, yield 161 mg (88%). H NMR (300 MHz, CDCl3, 25 °C): δ
= 1.34–1.44 (m, 3 H), 1.68–1.90 (m, 5 H), 1.96–2.08 (m, 2 H), 2.46
(s, 3 H), 6.95 (s, 1 H), 7.36 (d, J = 9.0 Hz, 2 H), 7.76 (d, J = 8.4 Hz,
2 H) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –140.4 (s, 2
1-{[(2,2-Difluoro-3,3-dimethylcyclopropylidene)(4-methoxyphenyl)-
methyl]sulfonyl}-4-methylbenzene (4aa): Solid, yield 40 mg (74%).
1H NMR (300 MHz, CDCl3, 25 °C): δ = 1.54 (s, 3 H), 1.59 (s, 3
H), 2.36 (s, 3 H), 3.79 (s, 3 H), 6.82 (d, J = 9.0 Hz, 2 H), 7.20 (d,
J = 7.8 Hz, 2 H), 7.46 (d, J = 9.0 Hz, 2 H), 7.58 (d, J = 8.1 Hz, 2
H) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –136.9 (s, 2
F) ppm. IR (film): ν = 3050, 2939, 2862, 1746, 1598, 1472, 1344,
˜
1321, 1169, 1147, 1115 cm–1. MS (EI): m/z: 312 [M]+ (15.84), 91
(100). C16H18F2O2S (312.1): C 61.52, H 5.81; found: C 61.63, H
5.77.
X-ray Crystallographic Data for 2f: Crystal system: monoclinic,
space group: P21/n, unit cell dimensions: a = 13.0719(18) Å, b =
5.9925(8) Å, c = 19.815(3) Å, α = 90°, β = 99.478(3)°, γ = 90°; Z =
4, F(000) = 656, R1 = 0.0734, wR2 = 0.1309. CCDC-289229 con-
tains the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
F) ppm. IR (film): ν = 2920, 1716, 1604, 1513, 1463, 1389, 1345,
˜
1324, 1304, 1257, 1183, 1151 cm–1. MS (EI): m/z: 378 [M]+ (4.12),
135 (100). C20H20F2O3S (378.1): C 63.48, H 5.33; found: C 63.57,
H 5.12.
1-{[(2,2-Difluoro-3,3-dimethylcyclopropylidene)(tolyl)methyl]-
sulfonyl}-4-methylbenzene (4ab): Solid, yield 108 mg (60%). 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 2.32 (s, 3 H), 2.36 (s, 3 H),
7.10 (d, J = 8.4 Hz, 2 H), 7.20 (d, J = 8.4 Hz, 2 H), 7.38 (d, J =
8.4 Hz, 2 H), 7.58 (d, J = 8.1 Hz, 2 H) ppm. 19F NMR (282 MHz,
1-{[(2,2-Difluoro-3,3-dimethylcyclopropylidene)methyl]sulfonyl}-4-
methylbenzene (2a): Solid, yield 108 mg (63 %). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 1.45 (t, J = 1.5 Hz, 6 H), 2.46 (s, 3
H), 7.00 (s, 1 H), 7.37 (d, J = 8.1 Hz, 2 H), 7.80 (d, J = 8.1 Hz, 2
H) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –138.7 (s, 2
CDCl , 25 °C): δ = –137.02 (s, 2 F) ppm. IR (film): ν = 2977, 2931,
˜
3
1715, 1597, 1512, 1458, 1389, 1347, 1319, 1303, 1147 cm–1. MS
(EI): m/z: 362 [M]+ (6.93), 119 (100). C20H20F2O2S (362.1): C
66.28, H 5.56; found: C 66.76, H 5.97.
F) ppm. IR (film): ν = 2982, 1744, 1594, 1490, 1461, 1394, 1342,
˜
1322, 1298, 1239, 1210, 1154 cm–1. MS (EI): m/z: 272 (100) [M+].
C13H14F2O2S (272.1): C 57.34, H 5.18; found: C 57.37, H 5.17.
1-{[(2,2-Difluoro-3,3-dimethylcyclopropylidene)(phenyl)methyl]-
sulfonyl}-4-methylbenzene (4ac): Solid, yield 191 mg (55%). 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 2.36 (s, 3 H), 7.22 (d, J =
1-{[(2-Ethyl-3,3-difluoro-2-methylcyclopropylidene)methyl]sulfonyl}-
4-methylbenzene (2d): Solid, yield 130 mg (80 %). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 1.09 (t, J = 7.2 Hz, 3 H), 1.44 (s, 3 8.1 Hz, 2 H), 7.30–7.37 (m, 3 H), 7.47–7.52 (m, 2 H), 7.59 (d, J =
H), 1.61–1.71 (m, 1 H), 1.99–2.09 (m, 1 H), 2.47 (s, 3 H), 6.99 (s, 8.1 Hz, 2 H) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –137.0
1 H), 7.39 (d, J = 7.2 Hz, 2 H), 7.78 (d, J = 8.1 Hz, 2 H) ppm. 19F
(s, 2 F) ppm. IR (film): ν = 2964, 2926, 2854, 1656, 1456, 1349,
˜
NMR (282 MHz, CDCl3, 25 °C): δ = –136.7 (d, J = 181.9 Hz, 1 1300, 1262, 1151, 1090 cm–1. MS (EI): m/z: 348 [M]+ (15.25), 105
F), –141.2 (d, J = 184.4 Hz, 1 F) ppm. IR (film): ν = 2984, 2939, (100). C19H18F2O2S (348.1): C 65.50, H 5.21; found: C 65.81, H
˜
2883, 1737, 1596, 1462, 1454, 1380, 1357, 1320, 1271, 1152 cm–1.
5.28.
Eur. J. Org. Chem. 2006, 5581–5587
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5585

Z.-L. Cheng, J.-C. Xiao, C. Liu, Q.-Y. Chen
FULL PAPER
1-{[(4-Chlorophenyl)(2,2-difluoro-3,3-dimethylcyclopropylidene)-
methyl]sulfonyl}-4-methylbenzene (4ad): Solid, yield 141 mg (37%).
1H NMR (300 MHz, CDCl3, 25 °C): δ = 1.56 (t, J = 1.5 Hz, 6 H),
2.38 (s, 3 H), 7.22 (d, J = 8.4 Hz, 2 H), 7.28 (d, J = 8.4 Hz, 2 H),
7.43 (d, J = 8.4 Hz, 2 H), 7.56 (d, J = 7.8 Hz, 2 H) ppm. 19F NMR
by flash chromatography on a silica gel column to provide 5a
(50 mg, 75%) as a white solid.
2-(2,2-Difluoro-3,3-dimethylcyclopropylidene)-1-phenyl-2-(tolyl-4-
sulfonyl)ethanol (5a): Solid, yield 50 mg (75 %). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 1.43 (d, J = 8.7 Hz, 6 H), 2.41 (s, 3
H), 2.87 (d, J = 4.5 Hz, 1 H), 5.58 (s, 1 H), 7.13–7.24 (m, 7 H), 7.57
(d, J = 7.8 Hz, 2 H) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ
= –135.2 (d, J = 181 Hz, 1 F), –137.1 (d, J = 181 Hz, 1 F) ppm.
(282 MHz, CDCl , 25 °C): δ = –136.97 (s, 2 F) ppm. IR (film): ν =
˜
3
2930, 1722, 1594, 1491, 1466, 1388, 1348, 1323, 1203, 1154,
1088 cm– 1 . MS (EI): m/z : 382 [M]+ (2.94), 139 (100).
C19H17ClF2O2S (382.1): C 59.61, H 4.48; found: C 59.89, H 4.66.
IR (film): ν = 3502, 2937, 1737, 1569, 1494, 1463, 1452, 1392, 1349,
˜
1315, 1221, 1146, 1088 cm–1. MS (EI): m/z: 378 [M]+ (1.09),
77(100). C20H20F2O3S (378.1): C 63.48, H 5.33; found: C 63.48, H
5.17.
Methyl 4-[(2,2-Difluoro-3,3-dimethylcyclopropylidene)(tolyl-4-
sulfonyl)methyl]benzoate (4ae): Solid, yield 102 mg (25 %). 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 1.57 (t, J = 2.1 Hz, 6 H), 2.36
(s, 3 H), 3.91 (s, 3 H), 7.21 (d, J = 7.8 Hz, 2 H), 7.55 (d, J = 1.8 Hz,
2 H), 7.57 (d, J = 2.1 Hz, 2 H), 7.97 (d, J = 8.1 Hz, 2 H) ppm. 19F
NMR (282 MHz, CDCl3, 25 °C): δ = –136.9 (s, 2 F) ppm. IR (film):
2-(2-Ethyl-3,3-difluoro-2-methylcyclopropylidene)-1-phenyl-2-(tolyl-
4-sulfonyl)ethanol (5b): Liquid, yield 216 mg (55 %). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 1.02–1.09 (m, 3 H), 1.40 (d, J =
9.3 Hz, 3 H), 1.56–1.69 (m, 1 H), 1.99–2.09 (m, 1 H), 2.41 (s, 3 H),
2.88 (dd, J = 1.2 Hz, 12.6 Hz, 1 H), 5.58 (br., 1 H), 7.12–7.27 (m,
7 H), 7.56 (d, J = 8.1 Hz, 2 H) ppm. 19F NMR (282 MHz, CDCl3,
25 °C): δ = –132.1 (d, J = 183.6 Hz, 0.25 F), –134.9 (d, J = 184 Hz,
0.25 F), –137.7 (d, J = 181.6 Hz, 0.25 F), –139.5 (d, J = 185.8 Hz,
ν = 2923, 2851, 1724, 1608, 1597, 1459, 1426, 1390, 1347, 1326,
˜
1316, 1276, 1157, 1142 cm–1. MS (EI): m/z: 406 [M]+ (4.62), 163
(100). HRMS (EI) calcd. for C21H20F2O4S: 406.1046: found:
406.1050.
1-{[(2-Ethyl-3,3-difluoro-2-methylcyclopropylidene)(methoxyphen-
yl)methyl]sulfonyl}-4-methylbenzene (4da): Solid, yield 223 mg
(57%). 1H NMR (300 MHz, CDCl3, 25 °C): δ = 1.14 (t, J = 7.2 Hz,
3 H), 1.55 (t, J = 1.8 Hz, 3 H), 1.69–1.82 (m, 1 H), 2.14–2.25 (m,
1 H), 2.38 (s, 3 H), 3.81 (s, 3 H), 6.84 (d, J = 8.7 Hz, 2 H), 7.22 (d,
J = 8.7 Hz, 2 H), 7.47 (d, J = 8.7 Hz, 2 H), 7.59 (d, J = 8.7 Hz, 2
H) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –134.7 (d, J =
0.25 F) ppm. IR (film): ν = 3497, 2975, 2939, 1598, 1495, 1456,
˜
1378, 1361, 1319, 1304, 1199, 1151, 1090 cm–1. MS (ESI): m/z:
409.7 [M + NH4]+. HRMS (MALDI) calcd. for C21H22F2O3SNa+:
415.1154; found: 415.1150.
2-(2-tert-Butyl-3,3-difluoro-2-methylcyclopropylidene)-1-phenyl-2-
(tolyl-4-sulfonyl)ethanol (5c): Liquid, yield 147 mg (70%). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 1.15 (d, J = 8.4 Hz, 9 H), 1.35 (d,
J = 15 Hz, 3 H), 2.40 (d, J = 5.4 Hz, 3 H), 2.82 (dd, J = 5.4,
62.7 Hz, 2 H), 5.59 (d, J = 3.3 Hz, 1 H), 7.07 (m, 1 H), 7.15–7.25
(m, 6 H), 7.35 (d, J = 5.4 Hz, 1 H), 7.61 (d, J = 7.8 Hz, 1 H) ppm.
19F NMR (282 MHz, CDCl3, 25 °C): δ = –126.5 (d, J = 186 Hz,
0.25 F), –129 (d, J = 187 Hz, 0.25 F), –135.7 (d, J = 188 Hz, 0.25
183.6 Hz, 1 F), –139.4 (d, J = 182.2 Hz, 1 F) ppm. IR (film): ν =
˜
2926, 1715, 1605, 1512, 1459, 1359, 1322, 1256, 1178, 1150 cm–1.
MS (EI): m/z: 392 [M]+ (8.72), 135 (100). HRMS (MALDI) calcd.
for C21H22O3F2SNa+: 415.1158; found: 415.1150.
1-{[(2-tert-Butyl-3,3-difluoro-2-methylcyclopropylidene)(methoxy-
phenyl)methyl]sulfonyl}-4-methylbenzene (4ea): Liquid, yield 263 mg
(60%). 1H NMR (300 MHz, CDCl3, 25 °C): δ = 1.21 (s, 9 H), 1.52
(t, J = 2.1 Hz, 3 H), 2.35 (s, 3 H), 6.81 (d, J = 9.0 Hz, 2 H), 7.20
(d, J = 8.4 Hz, 2 H), 7.38 (d, J = 9 Hz, 2 H), 7.54 (d, J = 8.4 Hz,
2 H) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –129.1 (d, J
F), –138.2 (d, J = 187 Hz, 0.25F) ppm. IR (film): ν = 3500, 2900,
˜
1600, 1450, 1320, 1232, 1149, 1087 cm–1. MS (ESI): m/z: 438.2 [M
+ NH4]+. HRMS (MALDI) calcd. for C23H26F2O3SNa+: 443.1469;
found: 443.1463.
= 184.4 Hz, 1 F), –138.5 (d, J = 186.1 Hz, 1 F) ppm. IR (film): ν
˜
2-(2,2-Difluorospiro[2.5]octylidene)-1-phenyl-2-(tolyl-4-sulfonyl)-
ethanol (5d): Solid, yield 127 mg (61 %). 1H NMR (300 MHz,
CDCl3, 25 °C): δ = 0.85 (t, J = 5.7 Hz, 3 H), 1.19–1.48 (m, 9 H),
1.60–1.70 (m, 2 H), 2.46 (s, 3 H), 4.38 (br., 1 H), 7.37 (d, J =
8.4 Hz, 2 H), 7.77 (d, J = 8.1 Hz, 2 H) ppm. 19F NMR (282 MHz,
CDCl3, 25 °C): δ = –134.8 (m, 0.2 F), –135.5 (m, 0.8 F), –136.1 (m,
= 2964, 2920, 1715, 1606, 1575, 1512, 1464, 1337, 1324, 1256,
1151 cm–1. MS (ESI): m/z: 438.2 [M + NH4]+. HRMS (MALDI)
calcd. for C23H27F2O3S+: 421.1635; found: 421.1643.
1,1-Difluoro-2-[(4-methoxyphenyl)(tolyl-4-sulfonyl)methylidene]-
spiro[2.5]octane (4fa): Solid, yield 138 mg (66 %). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 1.38–1.49 (m, 3 H), 1.76–1.93 (m, 5
H), 2.12–2.23 (m, 2 H), 2.36 (s, 3 H), 6.82 (d, J = 9.0 Hz, 2 H),
7.20 (d, J = 8.4 Hz, 2 H), 7.45 (d, J = 8.7 Hz, 2 H), 7.57 (d, J =
8.4 Hz, 2 H) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –138.4
0.8 F), –136.7 (m, 0.2F) ppm. IR (film): ν = 3491, 2964, 2932, 2873,
˜
1597, 1462, 1392, 1351, 1315, 1305, 1224, 1145, 1086 cm–1. MS
(ESI): m/z: 436.1 [M + NH4]+. C23H24F2O3S (436.1): C 66.01, H
5.78; found: C 66.30, H 5.58.
(s, 2 F) ppm. IR (film): ν = 2934, 1713, 1607, 1577, 1513, 1456,
˜
1375, 1324, 1305, 1260, 1162, 1148, 1112 cm–1. MS (ESI): m/z:
436.2 [M + NH4]+. C23H24F2O3S (418.1): C 66.01, H 5.78; found:
C 66.00, H 5.88.
1-(2,2-Difluoro-3,3-dimethylcyclopropylidene)-1-(tolyl-4-sulfonyl)-
pentan-2-ol (5f): Solid, yield 210 mg (51%). 1H NMR (300 MHz,
CDCl3, 25 °C): δ = 0.85 (t, J = 7.2 Hz, 3 H), 1.17–1.39 (m, 2 H),
1.43 (s, 6 H), 1.57–1.72 (m, 2 H), 2.46 (s, 3 H), 4.38 (br., 1 H), 7.37
(d, J = 8.1 Hz, 2 H), 7.77 (d, J = 8.7 Hz, 2 H) ppm. 19F NMR
(282 MHz, CDCl3, 25 °C): δ = –134.8 (m, 0.2 F), –135.5 (m, 0.8
Typical Procedure for Reactions between Compounds 2 and Electro-
philes: Compound 2a (54 mg, 0.2 mmol) and THF (3 mL) were
placed under N2 in a Schlenk tube containing a magnetic stirring
bar, the mixture was cooled to –78 °C with a dry ice/alcohol bath,
and nBuLi (0.15 mL, 1.6 , 1.1 equiv.) was added. After the mix-
ture had been stirred for 30 min at this temperature, benzaldehyde
(22 mg, 1.2 equiv.) was added, and the reaction mixture was stirred
for a further hour at the same temperature. The cool bath was
removed, saturated aq. NH4Cl (5 mL) was added, and the reaction
F), –136.1 (m, 0.8 F), –136.7 (m, 0.2F) ppm. IR (film): ν = 3491,
˜
2964, 2932, 2873, 1597, 1462, 1392, 1351, 1315, 1305, 1224,
1145 cm–1. MS (ESI): m/z: 362.1 [M + NH4]+. C17H22F2O3S
(344.1): C 59.30, H 6.40; found: C 59.27, H 6.62.
1-[1-(2,2-Difluoro-3,3-dimethylcyclopropylidene)ethylsulfonyl]-4-
methylbenzene (5g): Solid, yield 171 mg (60 %). 1H NMR
mixture was extracted with ethyl acetate (3ϫ10 mL). The combined (300 MHz, CDCl3, 25 °C): δ = 1.44 (t, J = 1.8 Hz, 6 H), 2.06 (s, 3
organic layer was washed with brine and dried with MgSO4. After
removal of solvent under reduced pressure, the residue was purified
H), 2.46 (s, 3 H), 7.37 (d, J = 8.4 Hz, 2 H), 7.75 (d, J = 8.4 Hz, 2
H) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –139.9 (s, 2
5586
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 5581–5587

Synthesis and Conversion of Difluoro(methylene)cyclopropanes
FULL PAPER
[2] a) M.-T. Lai, E. Oh, Y. Shin, H.-W. Liu, J. Org. Chem. 1992,
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1997, 53, 9497–9508; b) A. Shibuya, M. Okada, Y. Nakamura,
M. Kibashi, H. Horikawa, T. Taguchi, Tetrahedron 1999, 55,
10325–10340.
[5] a) Chemistry of Organic Fluorine Compounds II (Eds.: M. Hud-
lický, A. E. Pavlath), American Chemical Society: Washington,
DC, 1995; b) D. L. S. Brahams, W. P. Dailey, Chem. Rev. 1996,
96, 1585–1632; c) M. R. C. Gerstenberger, A. Haas, Angew.
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[6] F. Tian, V. K. Kruger, O. Bautista, J.-X. Duan, A.-R. Li, W. R.
Dolbier, Jr., Q.-Y. Chen, Org. Lett. 2000, 2, 563–564.
[7] a) Z.-L. Cheng, Q.-Y. Chen, Synlett 2006, 478–480 and refer-
ence cited therein; b) X. Cai, Y. Zhai, I. Ghiviriga, K. A. Ab-
boud, W. R. Dolbier, Jr., J. Org. Chem. 2004, 69, 4210–4215; c)
W. R. Dolbier, Jr., F. Tian, J.-X. Duan, A.-R. Li, S. Ait-Mo-
hand, O. Bautista, J. M. Baker, J. Crawford, P. Anselme, X. H.
Cai, A. Modzelewska, H. Koroniak, M. A. Batliste, Q.-Y.
Chen, J. Fluorine Chem. 2004, 125, 459–469.
F) ppm. IR (film): ν = 2979, 2930, 2874, 1752, 1597, 1461, 1446,
˜
1392, 1351, 1319, 1227, 1161 cm–1. MS (EI): m/z: 286 [M]+ (7.25),
65 (100). HRMS (MALDI) calcd. for C14H16F2O2SNa+: 309.0744;
found: 309.0731.
1-[(2,2-Difluoro-3,3-dimethylcyclopropylidene)iodomethylsulfonyl]-4-
methylbenzene (5h): Solid, yield 147 mg (37 %). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 1.48 (t, J = 1.5 Hz, 6 H), 2.48 (s, 3
H), 7.38 (d, J = 8.1 Hz, 2 H), 7.83 (d, J = 8.1 Hz, 2 H) ppm. 19F
NMR (282 MHz, CDCl3, 25 °C): δ = –141.8 (s, 2 F) ppm. IR (film):
ν = 2950, 1765, 1700, 1593, 1460, 1446, 1390, 1338, 1321, 1209,
˜
1159, 1149, 879 cm– 1 . MS (ESI): m/z: 399.0 [M + H+ ].
C13H13F2IO2S(398.0): C 39.21, H 3.29; found: C 39.36, H 3.47.
Typical Procedure for Ring-Opening Reactions between Compounds
2 and I2: CuI (3 mg, 10 mol-%) was added under N2 to a solution
of 2a (20 mg) and I2 (75 mg, 4.0 equiv.) in CH3CN (5 mL). The
mixture was heated to reflux with stirring and monitored by 19F
NMR spectroscopy. After completion, aq. Na2S2O3 was added and
the reaction mixture was extracted with ethyl acetate (3ϫ10 mL).
The combined organic layer was washed with brine and dried with
MgSO4 and, after removal of solvent under reduced pressure, the
residue was purified by flash chromatography on a silica gel column
to provide 6a (36 mg, 93%) as a pale yellow solid.
1-{[2-(Difluoroiodomethyl)-3-iodo-3-methylbut-1-enyl]sulfonyl}-4-
methylbenzene (6a): Solid, yield 36 mg (93%). 1H NMR (300 MHz,
CDCl3, 25 °C): δ = 2.10 (s, 3 H), 2.48 (s, 3 H), 7.39 (d, J = 8.4 Hz,
2 H), 7.70 (s, 1 H), 7.91 (d, J = 8.4 Hz, 2 H) ppm. 19F NMR
[8] A. Brandi, A. Goti, Chem. Rev. 1998, 98, 589–636.
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Sabol, Bioorg. Med. Chem. Lett. 1997, 7, 2665–2668; d) J. M.
Birchall, R. Fields, R. Haszeldine, R. J. McLean, J. Fluorine
Chem. 1980, 15, 487–495; e) M. J. Bunegar, R. Fields, R. N.
Haszeldine, J. Fluorine Chem. 1980, 15, 497–509.
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Coppola), Wiley, New York, 1984; b) E. Block, H. R. Jeon,
D. Putman, S.-Z. Zhang, Tetrahedron 2004, 60, 7525–7541; c)
R. W. M. Aben, S. Braverman, H. W. Scheeren, Eur. J. Org.
Chem. 2003, 5, 894–897; d) A. Padwa, D. N. Kline, J. Perumat-
tam, Tetrahedron Lett. 1987, 28, 913–916; e) A. J. Guildford,
R. W. Turner, J. Chem. Soc., Chem. Commun. 1983, 8, 466–467;
f) J. R. Bull, N. S. Desmond-Smith, S. J. Heggie, R. Hunter, F.-
C. Tien, Synlett. 1998, 8, 900–902.
[11] a) G. Fournet, G. Balme, J. Goré, Tetrahedron 1988, 44, 5809–
5820; b) S. Bräse, H. Wertal, D. Frank, D. Vidovié, A. de Mei-
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Zhou, X. Huang, W. Chen, Synlett 2003, 13, 2080–2082.
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4894–4900; b) B. Xu, M. Shi, Org. Lett. 2003, 5, 14151418; c)
L.-X. Shao, B. Xu, J.-W. Huang, M. Shi, Chem. Eur. J. 2006,
12, 510–517 and reference cited therein.
(282 MHz, CDCl , 25 °C): δ = –88.2 (s, 2 F) ppm. IR (film): ν =
˜
3
2924, 2852, 1596, 1580, 1494, 1458, 1391, 1317, 1305, 1203,
1155 cm–1. MS (ESI): m/z: 544.0 [M + NH4]+. HRMS (MALDI)
calcd. for C13H14F2I2O2SNa+: 548.8681; found: 548.8664.
1-{[2-(Difluoroiodomethyl)-3-iodo-3-methylpent-1-enyl]sulfonyl}-4-
methylbenzene (6d): Liquid, yield 216 mg (80 %). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 10.9 (t, J = 6.9 Hz, 3 H), 1.44–1.53
(m, 1 H), 2.00 (m, 4 H), 2.47 (s, 3 H), 7.38 (d, J = 8.4 Hz, 2 H),
7.73 (s, 1 H), 7.90 (d, J = 8.4 Hz, 2 H) ppm. 19F NMR (282 MHz,
CDCl , 25 °C): δ = –85.3 (s, 2 F) ppm. IR (film): ν = 2957, 2923,
˜
3
2852, 1736, 1596, 1581, 1455, 1385, 1328, 1305, 1247, 1199, 1152,
1086 cm–1. MS (MALDI) m/z: 541 [M + H+]. HRMS (MALDI)
calcd. for C14H16F2I2O2SNa+: 562.8820; found: 562.8821.
1-{[3,3-Difluoro-3-iodo-2-(1-iodocyclohexyl)prop-1-enyl]sulfonyl}-4-
methylbenzene (6f): Solid, yield 135 mg (95 %). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 1.10–1.25 (m, 1 H), 1.37–1.50 (m, 2
H), 1.65–1.81 (m, 5 H), 2.06–2.14 (m, 2 H), 2.49 (s, 3 H), 7.40 (d,
J = 7.8 Hz, 2 H), 7.80 (s, 1 H), 7.94 (d, J = 8.1 Hz, 2 H) ppm. 19F
NMR (282 MHz, CDCl3, 25 °C): δ = –88.8 (s, 2 F) ppm. IR (film):
ν = 3017, 2947, 2926, 2860, 2839, 1593, 1579, 1446, 1428, 1338,
˜
1318, 1304, 1251, 1217, 1156, 1143, 1084 cm–1. C16H18F2I2O2S
(565.9): C 33.94, H 3.20; found: C 34.23, H 3.19.
Acknowledgments
[15] M. Suginome, T. Matsuda, Y. Ito, J. Am. Chem. Soc. 2000, 122,
We thank the Natural Science Foundation of China (Nos.
20272026, 20032010, 20532040) for supporting this work.
11015–11016.
[16] a) S. E. Denmark, M. A. Harmata, K. S. White, J. Org. Chem.
1987, 52, 4031–4042; b) J. B. van der Linden, P. F. T. M.
van Asten, S. Braverman, B. Zwanenburg, Recl. Trav. Chim.
Pays-Bas 1995, 114, 51–60.
[1] For recent reviews, see: a) I. Nakamura, Y. Yamamoto, Adv.
Synth. Catal. 2002, 344, 111–129; b) A. Brandi, S. Cicchi, F. M.
Cordero, A. Goti, Chem. Rev. 2003, 103, 1213–1270.
Received: July 17, 2006
Published Online: October 13, 2006
Eur. J. Org. Chem. 2006, 5581–5587
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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