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S. Zhu et al. / Tetrahedron Letters 47 (2006) 5897–5900
When arylaldehyde 2,4,6-triisopropyl-benzenesulfonyl
hydrazone is refluxed with 2 M equiv of potassium
hydroxide in methanol solution, it undergoes complete
decomposition to give pentafluorophenyl diazomethane
1a in greater than 95% yield and 97% purity (Table 1,
entry 1). The crude products aryl diazomethane 1, after
general work-up, could be used without further purifica-
tion efficiently by reducing the potential hazard and
avoiding heating the tosyl salt in vacuo.
ing to find that the desired epoxide 2a was isolated in
quantitative yield (Table 2, entry 1).
1H NMR of epoxide 1a showed only two signals (dou-
blet) at d 4.50 ppm and d 4.00 ppm, which are attributed
to the two hydrogen atoms on the epoxide ring. Their
coupling constant is 1.2 Hz, which is consistent with that
of trans-epoxide (trans: J = 1–2 Hz).6 No cis-isomers
1
were detected based on the H NMR. This selectivity
may result from the strong electron-withdrawing prop-
erties of the fluorine atoms, which can efficiently stabi-
lize the ylide intermediates. Therefore, we hold that
this reaction undergoes thermodynamic control to give
the thermodynamically stable trans-isomers. Similar
reaction results were also found in our early report.4b
The introduction of fluorine atoms into organic mole-
cules profoundly influences their physical and biological
properties. Recently, there has been growing interest in
fluorine-containing aromatic compounds owing to their
unique physical properties. Herein, we report our
attempts to catalytically prepare the fluorine-containing
epoxides from diazo compounds.
Similarly, 2-nitrobenzaldehyde can also react with per-
fluorophenyl diazomethane 1a to give epoxide 2b in
89% yield. The trans-structure of the epoxide was also
proven by the X-ray diffraction analysis of epoxide 2b
(Fig. 1).
Sulfur ylides are known for their ability to react with
aldehydes, electron-poor alkenes and imines to form
epoxides, cyclopropanes, and aziridines. Therefore, we
wondered if the sulfur ylide generated from pentafluoro-
phenyl diazomethane (1a) could react with aldehydes to
give the corresponding epoxides.
It is clear from the crystal structure that the perfluoro-
phenyl and 2-nitrophenyl are in trans positions.
Initially, we used Rh2(OAc)4 to catalyze the decomposi-
tion of the diazocompound, and tetrahydrothiophene to
trap the metal carbenenoid (Scheme 2). When 4-nitro-
benzaldehyde was chosen as the substrate, it was pleas-
This reaction is very sensitive to the properties of the
aldehydes. When 4-bromobenzaldehyde was used as
the reactant, only trace amount of the desired product
epoxide 2c was detected after 24 h at room temperature.
Enhancing the reaction temperature to 66 °C (refluxing
in THF), epoxide 2c was isolated in 64% yield. But when
benzaldehyde was used as the reactant, only trace prod-
uct was detected by 1H NMR in the refluxing THF. Fur-
ther enhancing the reaction temperature to 80 °C
(refluxing in benzene) and 110 °C (refluxing in toluene)
did not improve the yield of product 2d (Table 2, entry
4). We think that the sulfur ylide, generated in situ from
diazocompound 1a and sulfide, was not reactive enough
to attack the benzaldehyde due to the strong electron-
withdrawing properties of the fluorine atoms.
Table 1. Synthesis of aromatic diazomethane 1 using the Bamford–
Stevens reaction
Entry
Ar
Time (min)
Yielda (%)
Purityb (%)
1
2
C6F5 (1a)
C6H5 (1b)
4
7
>95
>95
>97
>97
a Crude yield.
b Determined by 1H NMR.
1mol%Rh2(OAc)4
Tetrahydrothiophene
O
As mentioned above, tellurium ylide is famous for its
high reactivity. It is more reactive than the correspond-
ing sulfur ylide.1f Therefore, we envisioned that the
tellurium ylide could react with benzaldehyde or the
electron-donating group substituted aryl aldehydes to
give the corresponding epoxide products. Under the
similar reaction conditions, benzaldehyde was consumed
C6F5CHN2
+
ArCHO
THF
C6F5
Ar
2
1a
trans:cis>99:1
Ar'CHO
X=CHAr
Rh2(OAc)4
ArCHN2
1
O
in two hours at room temperature. However, the H
N2
Rh=CHAr
NMR showed that the isolated product was alkene 3a,
not the desired epoxide. Alkene 3a was obtained in
quantitative yield and with complete trans-selectivity
(Scheme 3, Table 3, entry 1).
X
Ar
Ar'
X = R2S
Scheme 2.
Table 2. Synthesis of epoxides 2 through sulfur ylide intermediates
Entry
ArCHO (Ar =)
Temperature
Product
Yielda (%)
Trans:cisb
1
2
3
4
p-NO2C6H4–
o-NO2C6H4–
p-BrC6H4–
C6H5–
rt
rt
Reflux
Reflux
2a
2b
2c
2d
100
89
64
>99:1
>99:1
>99:1
—
Trace
a Isolated yield.
b Determined by 1H NMR.