Magnesium metal-mediated reductive trifluoromethylation of aldehydes with phenyl trifluoromethyl sulfone

Article abstract of DOI:10.1055/s-0029-1218752

An unprecedented reductive nucleophilic trifluoromethylation of aldehydes by using phenyl trifluoromethyl sulfone is reported. Mercury(II) chloride efficiently activates magnesium metal to induce the desulfonylative trifluoromethylation process. The new r

Full text of DOI:10.1055/s-0029-1218752

SPECIAL TOPIC
1899
Magnesium Metal-Mediated Reductive Trifluoromethylation of Aldehydes
with Phenyl Trifluoromethyl Sulfone
T
Y
rifluoromethylati
a
on of
A
ldeh
n
ydes chuan Zhao, Jieming Zhu, Chuanfa Ni, Jinbo Hu*
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
45 Ling-Ling Road, Shanghai 200032, P. R. of China
3
E-mail: jinbohu@sioc.ac.cn
Received 28 February 2010
der the reductive conditions appeared to be more chal-
lenging.3b Although an alkoxide-induced nucleophilic
trifluoromethylation with 1 has been developed, the meth-
od is only suitable for non-enolizable carbonyl com-
Abstract: An unprecedented reductive nucleophilic trifluorometh-
ylation of aldehydes by using phenyl trifluoromethyl sulfone is re-
ported. Mercury(II) chloride efficiently activates magnesium metal
to induce the desulfonylative trifluoromethylation process. The new
3f
reductive trifluoromethylation provides an alternative method for pounds. Because of the low cost and ready availability of
efficient trifluoromethylation of non-enolizable or enolizable alde- phenyl trifluoromethyl sulfone (1) (Scheme 1), which is
hydes with readily available phenyl trifluoromethyl sulfone reagent.
3b
also a precursor of trimethyl(trifluoromethane)silane,
Key words: alkylations, aldehydes, alcohols, trifluoromethyla- further exploration of the synthetic applications of the sul-
tions, phenyl trifluoromethyl sulfone
fone under milder conditions is desirable. Here, we report
a reductive nucleophilic trifluoromethylation of carbonyl
compounds by using phenyl trifluoromethyl sulfone (1),
The selective introduction of a trifluoromethyl (CF3) which is commercially available and can also be prepared
group into an organic molecule is a strategy that is fre- from methyl phenyl sulfide (2) through chlorination, flu-
quently used in drug design and agrochemical develop- orination, and oxidation (Scheme 1).5
ment because of the profound changes in bioactivity that
occur when a methyl group is replaced by a trifluoro-
methyl group. As a result, a variety of nucleophilic, elec-
O O
Cl2
HF
H2O2
1
S
PhSCH3
PhSCCl3
PhSCF3
AcOH
Ph
CF3
trophilic, and free-radical trifluoromethylation methods
3
2
4
1
2
have been developed, among which the nucleophilic tri-
Scheme 1 Synthesis of phenyl trifluoromethyl sulfone (1)
fluoromethylation reactions have been most extensively
2
a–g
–
3
studied.
Because the trifluoromethyl anion (CF ) is
highly unstable, various compounds with the structure Reductive alkylation through desulfonylation remains a
XCF3 [X = H, Br, I, SPh, TMS, SO Ph, C(O)Y; relatively poorly studied reaction (especially when com-
2
1
2
3
Y = NR R , OR, Ph] are normally used as synthons for pared with Barbier-type and Grignard-type reactions),
the trifluoromethyl anion in nucleophilic trifluorometh- partly because of the greater dissociation energy of the C–
6
ylation reactions. The strategies for transferring the CF3 S bond compared with the C–X (X = Br, I) bond. As a re-
group and breaking the X–C bond in XCF can be gener- sult, reductive desulfonylation generally requires harsher
3
ally categorized into two types: a) electron transfer from a reaction conditions than do reductive dehalogenation re-
suitable reducing agent to XCF (X = Br, I, SPh, actions. Indeed, the known desulfonylative alkylation re-
3
2
h,3a,b
SO Ph),
and b) nucleophilic attack of X in XCF
actions usually employ relatively expensive samarium
2
3
1
2
7
8
[
X = H, SPh, TMS, SO Ph, C(O)Y (Y = NR R , OR, diiodide or lithium naphthalenide as a reducing agent,
2
3
c–g
Ph)]
to cleave the X–C bond of XCF . Because of the which hampered their widespread adoption. We envis-
3
relatively low bond-dissociation energy of XCF (X = I, aged that phenyl trifluoromethyl sulfone (1) might act as
3
TMS) and the ease with which these undergo reduction or a good electron acceptor because of the high electron-
nucleophilic attack, trifluoro(iodo)methane and trimeth- withdrawing ability of the trifluoromethyl group and that
yl(trifluoromethane)silane (Ruppert–Prakash reagent) are the consequent reductive trifluoromethylation should pro-
considered to be the most versatile reagents of types a) ceed smoothly.
and b), respectively.
Initial results were, however, quite discouraging. We
Previously, we were interested in the exploration of syn- found that reducing agents such as magnesium, alumi-
4
thetic applications of fluorinated sulfones. Although the num, zinc, or samarium diiodide in various solvents led to
reductive trifluoromethylation of chlorosilanes by using recovery of phenyl trifluoromethyl sulfone (1). After
phenyl trifluoromethyl sulfone (1) was successfully screening of several metal salts as additives for activating
achieved in 2003, reactions with carbonyl compounds un- the reducing metals, we found that mercury(II) chloride
efficiently activates magnesium to induce the required
desulfonylation reaction (Table 1). The solvent also plays
an important role in the desulfonylation reaction, as the re-
action only occurs in highly polar solvents such as N,N-
SYNTHESIS 2010, No. 11, pp 1899–1904
x
x.
x
x
.
2
0
1
0
Advanced online publication: 23.04.2010
DOI: 10.1055/s-0029-1218752; Art ID: C00810SS
Georg Thieme Verlag Stuttgart · New York
©

1
900
Y. Zhao et al.
SPECIAL TOPIC
dimethylformamide or dimethyl sulfoxide, which facili- of this new nucleophilic trifluoromethylation reaction be-
tate the electron-transfer process and stabilize the anionic tween 1 and carbonyl compounds 5a–l. On treatment with
intermediate.
sulfone 1, various aldehydes reacted smoothly to the cor-
responding trifluoromethyl carbinols 6 in moderate-to-
good yields (Table 3; entries 1–8, 10–12). Aldehydes with
strong electron-withdrawing groups gave lower yields be-
cause of the rapid reduction and pinacol coupling of these
substrates under the reductive conditions (entries 3, 5, 8,
and 9). Moreover, under the reductive trifluoromethyla-
tion conditions, the enolizable aldehyde 5l gave an accept-
able yield that was superior to that of the previously
developed alkoxide-induced nucleophilic trifluorometh-
Table 1 Effects of the Reaction Conditions on the Reductive
Desulfonylation of Phenyl Trifluoromethyl Sulfone (1)
a
reducing metal (1 equiv)
O
O
additive (5 mol%)
S
HCF3
Ph
CF3
solvent
1
b
Entry Reducing metal Solvent
Additive
Conv. (%)
3
f
1
2
3
4
5
6
7
Mg
Mg
Mg
Mg
Mg
Mg
Zn
DMF
DMF
DMF
DMF
THF
NiCl2
0
0
ylation. Note that the magnesium–mercury(II) chloride–
methanol system is used extensively in reductive desulfo-
PbCl2
9
nylation reactions, but, to the best of our knowledge, the
CuBr2
HgCl2
HgCl2
HgCl2
HgCl2
HgCl2
0
corresponding desulfonylative alkylation reaction in a
nonprotic solvent has never been reported.
>99
0
Note that, unlike fluoride-induced nucleophilic trifluo-
romethylation with trimethyl(trifluoromethyl) silane, our
–
3
method generates the CF species (or its synthetic equiv-
DMSO
DMF
DMF
>99
0
alent) in the presence of a strong Lewis acid, so that sub-
strates with a low electrophilicity (such as N,N-
8
Al
0
O
O
OH
H
a
For all cases, PhSO CF was added to a mixture of reducing metal,
S
Mg, HgCl2, BF3⋅OEt2
DMF, −15 °C to r.t.
3 M HCl
2
3
CF3
additive, and solvent at r.t.
F3C
OH
b
Determined by 19F NMR of the crude reaction mixture, and based on
the consumption of 1.
4
7
7% 19F NMR
H
Next, we chose anisaldehyde (5a) as a model compound
N
NH2
to optimize the reactant ratio and reaction temperature
(
Table 2). We found that when the reactant ratio 1/5a/Mg/
O2N
NO2
H
N
N
H
HgCl was 2:1:2:0.06 and the reaction temperature
ranged between –15 °C and room temperature, the corre-
sponding trifluoromethylated product 6a was obtained in
2
7
CF3
NO2
O2N
1
7%
8
8% yield (Table 2, entry 4).
Having determined the optimal reaction conditions
Table 2, entry 4), we evaluated the scope and limitations
8
Scheme 2 Synthesis and trapping of the hydrated form of the
trifluoroacetaldehyde (fluoral)
(
Table 2 Effects of the Reaction Conditions for Reductive Desulfonylation Trifluoromethylation with Phenyl Trifluoromethyl Sulfone (1)
OH
CHO
O
O
Mg, HgCl2
solvent
CF3
+
S
Ph
CF3
MeO
MeO
1
5a
6a
Entry
Temp (°C)
Molar ratio
/5a/Mg
HgCl (mol%)a
Solvent
Yield (%)b
2
1
1
2
3
4
–50 °C to r.t.
–50 °C to r.t.
0 °C to rt
1:1:1
3
3
6
3
2
DMF
DMF
DMF
DMF
DMSO
50
80
79
88
28c
2:1:2
1.5:1:1.5
2:1:2
–15 °C to r.t.
r.t.
5
1:1:2
a
Relative to the amount of Mg metal used.
Isolated yield.
b
c
Determined by 19F NMR spectroscopy.
Synthesis 2010, No. 11, 1899–1904 © Thieme Stuttgart · New York

SPECIAL TOPIC
Trifluoromethylation of Aldehydes
1901
Table 3 Reductive Desulfonylation–Trifluoromethylation of Aldehydes with Phenyl Trifluoromethyl Sulfone (1)
O
OH
Mg, HgCl2 (3 mol%)
O
O
S
+
R1
H
DMF, −15 °C to r.t.
R1
CF3
Ph
CF3
H
1
5
6
Entrya
Substrate
Product
Yield (%)b
1
2
3
4
5
6
7
8
9
6a R = 4-MeO
6b R = 3,4-(MeO)2
6c R = 2-Cl
6d R = 4-Ph
6e R = 3-Cl
6f R = 4-t-Bu
6g R = 4-BnO
6h R = 2,4-Cl2
88
82
60
72
53
69
78
45
28
CHO
HO
R
CF3
R
5
a–i
6i R = 4-O N
2
OH
CF3
CHO
1
1
1
0
6j
6k
6l
55
60
45
5j
HO
CF3
CHO
1
5k
OH
CF3
CHO
2c
5l
a
b
c
In all cases, the molar ratio of reactants was 1/5/Mg/HgCl = 2.0:1.0:2.0:0.06.
Isolated yield.
2
MgCl was added to neutralize the basicity of the reaction system.
2
O
O–
O
O
O
Mg, HgCl2
R
H
–CF3
(1)
S
S
+
CF3
2 e–
Ph
O–
R
CF3
Ph
H
1
9
6
Br
O
O
Mg, HgCl2
DMF
S
O
O
(2)
S
Ph
CF3
DMF, 60 °C
1
0
1
7
7%
Scheme 3 Proposed mechanism for the trifluoromethylation reaction
dimethylformamide) can also be trifluoromethylated. In- With regard to the reaction mechanism of the trifluoro-
deed, we found that in the absence of aldehydes, the reac- methylation with trifluoromethyl sulfone 1, we propose
tion mixture produced the hydrated form of the that a single-electron transfer from magnesium metal to 1
trifluoroacetaldehyde (fluoral) in 77% yield (determined facilitates reductive desulfonylation to form an anionic
1
9
by F NMR). The formation of trifluoroacetaldehyde was trifluoromethyl species and magnesium benzenesulfinate
confirmed by the observation that when we treated the re- 9 (Scheme 3, equation 1). The formation of benzenesulfi-
action mixture with (2,4-dinitrophenyl)hydrazine 7, the nate species 9 is supported by the fact that when we treat-
condensed product 8 could be isolated and characterized ed the reaction mixture with (bromomethyl)benzene, the
(
Scheme 2). The low yield (17%) is partially due to de- benzylated product 10 was isolated in 77% yield
composition of compound 8 during purification by col- (Scheme 3, equation 2).
umn chromatography on silica gel (Scheme 2).
Synthesis 2010, No. 11, 1899–1904 © Thieme Stuttgart · New York

1
902
Y. Zhao et al.
SPECIAL TOPIC
1
In conclusion, we have developed a novel nucleophilic tri-
fluoromethylation method for aldehydes by using phenyl
trifluoromethyl sulfone through a magnesium metal-
mediated reductive desulfonylation process. The method
H NMR: d = 7.66–7.57(m, 6 H), 7.48–7.35 (m, 3 H), 5.09 (q,
J = 6.1 Hz, 1 H), 1.93 (br s, 1 H).
1
9
F NMR: d = –78.25 (d, J = 6.5 Hz, 3 F).
+
MS (EI, 70 eV): m/z (%) = 252 (39.3) [M ], 183 (100.0), 155 (80.6),
provides an alternative approach for efficient trifluoro- 77 (13.0).
methylation of both nonenolizable and enolizable alde-
1
-(3-Chlorophenyl)-2,2,2-trifluoroethanol (6e)
hydes with a readily available reagent.
The physical and spectroscopic data were identical to those reported
in the literature.
1
2
Unless otherwise mentioned, solvents and reagents were purchased
from commercial sources and used as received. DMF was distilled
1
H NMR: d = 7.50 (s, 1 H), 7.43–7.31 (m, 3 H), 5.01 (q, J = 7.0 Hz,
1
1
H), 2.73 (br s, 1 H).
1
13
19
from CaH , and THF was distilled from Na. H, C, and F NMR
2
9
spectra were recorded on a 300-MHz NMR spectrometer (Bruker
F NMR: d = –78.33 (d, J = 6.2 Hz, 3 F).
1
AM300). H NMR chemical shifts were determined relative to in-
+
MS (EI, 70 eV): m/z (%) = 210 (13.7) [M ], 141 (81.9), 113 (43.3),
77 (100.0).
ternal TMS (d = 0.0) or to the signals of solvent CDCl (d = 7.26).
3
1
3
C NMR chemical shifts were determined relative to internal TMS
d = 0.0) or solvent CDCl (d = 77.0). F NMR chemical shifts were
determined relative to CFCl (d = 0.0). Mass spectra were recorded
1
9
(
3
1-(4-tert-Butylphenyl)-2,2,2-trifluoroethanol (6f)
The physical and spectroscopic data were identical to those reported
in the literature.
1
3
on a HP5973N (Agilent) mass spectrometer. HRMS were recorded
on a Saturn 2000 high-resolution mass spectrometer in the EI or ESI
mode.
13
H NMR: d = 7.44 (d, J = 8.7 Hz, 2 H), 7.40 (d, J = 8.7 Hz, 2 H),
.99 (q, J = 6.6 Hz, 1 H), 2.30 (br s, 1 H), 1.33 (s, 9 H).
4
1
9
Trifluoromethylation of Aldehydes 5; General Procedure
F NMR: d = –78.39 (d, J = 6.8 Hz, 3 F).
PhSO CF (1; 210 mg, 1 mmol) and aldehyde 5 (0.5 mmol) in DMF
+
2
3
MS (EI, 70 eV): m/z (%) = 232 (17.6) [M ], 217 (100.0), 189 (15.9),
9
(
2 mL) were added dropwise to a suspension of HgCl (8 mg, 0.03
2
1 (14.0).
mmol) and Mg (24 mg, 1 mmol) in DMF (2 mL) at –15 °C. The
mixture was allowed to warm to r.t. and, upon disappearance of Mg
1
-[4-(Benzyloxy)phenyl]-2,2,2-trifluoroethanol (6g)
(
~2 h), the reaction was quenched with 3 N HCl (1.5 mL). The mix-
The physical and spectroscopic data were identical to those reported
ture was then extracted with Et O (3 × 15 mL). The combined or-
14
2
in the literature.
1
ganic phase was washed with brine then dried (MgSO ), filtered,
4
H NMR: d = 7.44–7.27 (m, 7 H), 6.96 (d, J = 8.2 Hz, 2 H), 5.02 (s,
and concentrated under vacuum to give a crude product that was pu-
rified by silica gel chromatography (EtOAc–petroleum ether).
2
1
H), 4.84 (q, J = 6.6 Hz, 1 H), 2.78 (br s, 1 H).
9
F NMR: d = –78.95 (d, J = 6.6 Hz, 3 F).
2
,2,2-Trifluoro-1-(4-methoxyphenyl)ethanol (6a)
+
MS (EI, 70 eV): m/z (%) = 282 (12.3) [M ], 278 (5.4), 139 (8.1), 91
(100.0).
The physical and spectroscopic data were identical to those reported
in the literature.10
1
H NMR: d = 7.40 (d, J = 8.3 Hz, 2 H), 6.93 (d, J = 8.6 Hz, 2 H),
1
-(2,4-Dichlorophenyl)-2,2,2-trifluoroethanol (6h)
4
1
.97 (q, J = 6.6 Hz, 1 H), 3.83 (s, 3 H), 2.39 (br s, 1 H).
IR (film): 1708, 1593, 1477, 1385, 1269, 1178, 1133, 1108, 1085,
1046, 871, 849, 817, 778, 691, 459 cm .
–
1
9
F NMR: d = –78.66 (d, J = 6.6 Hz, 3 F).
1
+
H NMR: d = 7.63 (d, J = 8.6 Hz, 1 H), 7.43 (d, J = 1.7 Hz, 1 H),
MS (EI, 70 eV): m/z (%) = 206 (2.7) [M ], 137 (100.0), 109 (38.2).
7
.34 (dd, J = 8.3 Hz, J = 1.7 Hz 1 H), 5.58 (q, J = 6.5 Hz, 1 H), 2.88
(
19
br s, 1 H).
1
-(3,4-Dimethoxyphenyl)-2,2,2-trifluoroethanol (6b)
The physical and spectroscopic data were identical to those reported
F NMR: d = –78.56 (d, J = 6.1 Hz, 3 F).
in the literature.11
1
3
C NMR: d = 136.1, 134.4, 130.4, 129.9, 129.4, 127.7, 123.9 (q,
1
H NMR: d = 6.94 (m, 1 H), 6.89 (m, 2 H), 5.23 (q, J = 7.2 Hz, 1 H),
J = 282.7 Hz), 68.3 (q, J = 33.4 Hz).
3
.84 (s, 3 H), 3.78 (s, 3 H), 3.61 (br s, 1 H).
+
MS (EI, 70 eV): m/z (%) = 244 (24.9) [M ], 175 (100.0), 111 (65.5),
5 (24.5).
1
9
F NMR: d = –78.39 (d, J = 6.5 Hz, 3 F).
7
+
MS (EI, 70 eV): m/z (%) = 236 (100.0) [M ], 219 (41.6), 167 (81.7),
1
HRMS (EI): m/z calcd for C H Cl F O: 243.9670; found: 243.9671.
8
5
2 3
39 (80.7).
2
,2,2-Trifluoro-1-(4-nitrophenyl)ethanol (6i)
1
-(2-Chlorophenyl)-2,2,2-trifluoroethanol (6c)
The physical and spectroscopic data were identical to those reported
in the literature.
The physical and spectroscopic data were identical to those reported
15
in the literature.12
1
H NMR: d = 8.29 (d, J = 8.7 Hz, 2 H), 7.70 (d, J = 8.6 Hz, 2 H),
1
H NMR: d = 7.70 (m, 1 H), 7.43–7.33 (m, 3 H), 5.65 (m, 1 H), 2.74
d, J = 3.7 Hz, 1 H).
5
.19 (q, J = 6.6 Hz, 1 H), 2.79 (br s, 1 H).
(
1
9
F NMR: d = –78.73 (d, J = 6.3 Hz, 3 F).
1
9
F NMR: d = –77.96 (d, J = 6.1 Hz, 3 F).
+
MS (EI, 70 eV): m/z (%) = 221 (89.5) [M ], 152 (100.0), 127 (32.5),
7
+
MS (EI, 70 eV): m/z (%) = 210 (34.0) [M ], 141 (100.0), 113 (18.3),
7
8 (39.3).
7 (87.2), 51 (15.4).
2
,2,2-Trifluoro-1-(2-naphthyl)ethanol (6j)
1
-Biphenyl-4-yl-2,2,2-trifluoroethanol (6d)
The physical and spectroscopic data were identical to those reported
in the literature.
The physical and spectroscopic data were identical to those reported
15
for this compound.3
f
1
H NMR: d = 7.96 (s, 1 H), 7.93–7.83 (m, 3 H), 7.61–7.45 (m, 3 H),
5
.20 (q, J = 6.8 Hz, 1 H), 2.38 (br s, 1 H).
Synthesis 2010, No. 11, 1899–1904 © Thieme Stuttgart · New York

SPECIAL TOPIC
Trifluoromethylation of Aldehydes
1903
1
9
F NMR: d = –78.08 (d, J = 6.6 Hz, 3 F).
2004, 5, 637. (h) Jeschke, P. ChemBioChem 2004, 5, 570.
(i) Kirsch, P.; Bremer, M. Angew. Chem. Int. Ed. 2000, 39,
+
MS (EI, 70 eV): m/z (%) = 226 (47.8) [M ], 209 (15.0), 157 (63.0),
1
4217.
29 (100.0).
(
2) (a) Prakash, G. K. S.; Yudin, A. K. Chem. Rev. 1997, 97,
7
57. (b) Prakash, G. K. S.; Mandal, M. J. Fluorine Chem.
2
,2,2-Trifluoro-1-(1-naphthyl)ethanol (6k)
2
001, 112, 123. (c) Prakash, G. K. S.; Hu, J. In Fluorine-
The physical and spectroscopic data were identical to those reported
in the literature.15
Containing Synthons; Soloshonok, V. A., Ed.; American
Chemical Society: Washington DC, 2005. (d) Singh, R. P.;
Shreeve, J. M. Tetrahedron 2000, 56, 7613. (e) Langlois, B.
R.; Billard, T. Tetrahedron 2003, 185. (f) McClinton, M.
A.; McClinton, D. A. Tetrahedron 1992, 48, 6555.
1
H NMR: d = 8.04 (d, J = 8.7 Hz, 1 H), 7.95–7.85 (m, 2 H), 7.82 (d,
J = 7.1 Hz, 1 H), 7.62–7.46 (m, 3 H), 5.87 (q, J = 6.5 Hz, 1 H), 2.47
(
br s, 1 H).
1
9
(g) Burton, D. J.; Yang, Z. Y. Tetrahedron 1992, 48, 189.
F NMR: d = –77.31 (d, J = 6.6 Hz, 3 F).
(
h) Médebielle, M.; Dolbier, W. R. Jr. J. Fluorine Chem.
+
MS (EI, 70 eV): m/z (%) = 226 (41.8) [M ], 209 (7.5), 157 (66.8),
1
2008, 129, 930. (i) Umemoto, T. Chem. Rev. 1996, 96,
1757. (j) Ma, J.-A.; Cahard, D. J. Fluorine Chem. 2007, 128,
975. (k) Ma, J.-A.; Cahard, D. Chem. Rev. 2004, 104, 6119.
29 (100.0).
1
,1,1-Trifluoro-4-phenylbutan-2-ol (6l)
(
l) Shibata, N.; Mizuta, S.; Kawai, H. Tetrahedron:
The physical and spectroscopic data were identical to those reported
Asymmetry 2008, 19, 2633.
in the literature.10
(
3) For selected examples, see: (a) Kitazume, T.; Ishikawa, N.
J. Am. Chem. Soc. 1985, 107, 5186. (b) Prakash, G. K. S.;
Hu, J. B.; Olah, G. A. J. Org. Chem. 2003, 68, 4457.
(c) Large, S.; Roques, N.; Langlois, B. R. J. Org. Chem.
1
H NMR: d = 7.37–7.27 (m, 2 H), 7.27–7.16 (m, 3 H), 3.89 (m, 1
H), 2.91 (m, 1 H), 2.77 (m, 1 H), 2.00 (m, 3 H).
1
9
F NMR: d = –79.87 (d, J = 6.4 Hz, 3 F).
2
1
000, 65, 8848. (d) Yokoyama, Y.; Mochida, K. Synlett
996, 1191. (e) Prakash, G. K. S.; Mandal, M. J. Fluorine
+
MS (EI, 70 eV): m/z (%) = 204 (12.7) [M ], 117 (31.4), 91 (100.0),
5 (13.9).
6
Chem. 2001, 112, 123. (f) Prakash, G. K. S.; Hu, J. B.; Olah,
G. A. Org. Lett. 2003, 5, 3253. (g) Joubert, J.; Roussel, S.;
Christophe, C.; Billard, T.; Langlois, B. R.; Vidal, T. Angew.
Chem. Int. Ed. 2003, 42, 3133.
(
2E)-1-(2,4-dinitrophenyl)-2-(2,2,2-trifluoroethylidene)hydra-
zine (8)
The physical and spectroscopic data were identical to those in the
(
(
4) (a) Hu, J. J. Fluorine Chem. 2009, 130, 1130. (b) Hu, J.;
Zhang, W.; Wang, F. Chem. Commun. (Cambridge) 2009,
7465. (c) Prakash, G. K. S.; Hu, J. Acc. Chem. Res. 2007, 40,
921.
literature.16
1
H NMR: d = 11.37 (s, 1 H), 9.12 (s, 1 H), 8.44 (dd, J = 9.6 Hz,
J = 2.7 Hz, 1 H), 8.04 (d, J = 9.6 Hz, 1 H), 7.50 (q, J = 3.8 Hz, 1 H).
5) (a) Yagupol’skii, L. M.; Marenets, M. S. Zh. Obshch. Khim.
1
9
F NMR: d = –66.51 (d, J = 3.8 Hz, 3 F).
1
954, 24, 887. (b) Lu, T. C. CN 1746155 (A), 2006; Chem.
+
MS (EI, 70 eV): m/z (%) = 278 (67.1) [M ], 259 (15.7), 79 (100.0),
5 (43.3), 63 (57.6), 51 (43.0).
Abstr. 2006, 145, 103425. (c) Kremsner, J. M.; Rack, M.;
7
Pilger, C.; Kappe, C. O. Tetrahedron Lett. 2009, 50, 3665.
(
d) Chen, Q.; Duan, J. J. Chem. Soc., Chem. Commun. 1993,
Benzyl Phenyl Sulfone (10)
918.
The physical and spectroscopic data were identical to those reported
(6) Nájera, C.; Yus, M. Tetrahedron 1999, 55, 10547.
(7) For selected examples, see: (a) Trost, B. M.; Neilsen, J. B.;
Hoogsteen, K. J. Am. Chem. Soc. 1992, 114, 5432.
in the literature.17
1
H NMR: d = 7.96–7.56 (m, 3 H), 7.45 (t, J = 7.5 Hz, 2 H), 7.36–
(b) Mazéas, D.; Skrydstrup, T.; Beau, J. M. Angew. Chem.
7
.21 (m, 3 H), 7.10 (d, J = 7.6 Hz, 2 H), 4.31 (s, 2 H).
Int. Ed. 1995, 34, 909. (c) Jarreton, O.; Skrydstrup, T.;
Beau, J. M. Tetrahedron Lett. 1997, 38, 1767.
+
MS (EI, 70 eV): m/z (%) = 232 (3.9) [M ], 91 (100.0).
(d) Skrydstrup, T.; Jarreton, O.; Mazéas, D.; Urban, D.;
Beau, J. M. Chem. Eur. J. 1998, 4, 655. (e) Krintel, S. L.;
Jiménez-Barbero, J.; Skrydstrup, T. Tetrahedron Lett. 1999,
40, 7565. (f) Jarreton, O.; Skrydstrup, T.; Espinosa, J. F.;
Jiménez-Barbero, J.; Beau, J. M. Chem. Eur. J. 1999, 5,
430. (g) Katritzky, A. R.; Feng, D. M.; Qi, M. J. Org. Chem.
1997, 62, 6222. (h) Dong, J. C.; Kou, B. B.; Li, R. T.;
Cheng, T. M. Synth. Commun. 2002, 32, 935.
Acknowledgment
This work was supported by the National Natural Science Founda-
tion of China (20772144, 20825209, 20832008) and the Chinese
Academy of Sciences (Hundreds-Talent Program and Knowledge
Innovation Program).
(
(
8) For selected examples, see: (a) Yu, J. R.; Cho, H. S.;
Chandrasekhar, S.; Falck, J. R.; Mioskowski, C.
References
Tetrahedron Lett. 1994, 35, 5437. (b) Yu, J. R.; Cho, H. S.;
Falck, J. R. J. Org. Chem. 1993, 58, 5892. (c) Guijarro, D.;
Yus, M. Tetrahedron Lett. 1994, 35, 2965. (d) Alonso, D.
A.; Alonso, E.; Nájera, C.; Ramón, D. J.; Yus, M.
Tetrahedron 1997, 53, 4835.
(
1) (a) Bégué, J.-P.; Bonnet-Delpon, D. Bioorganic and
Medicinal Chemistry of Fluorine; Wiley-VCH: Weinheim,
2
008. (b) Kirsch, P. Modern Fluoroorganic Chemistry:
Synthesis, Reactivity, Applications; Wiley-VCH: Weinheim,
004. (c) Organofluorine Compounds: Chemistry and
Applications, Yamamoto H.; Springer: New York, 2000.
d) Ren, J.; Milton, J.; Weaver, K. L.; Short, S. A.; Stuart, D.
2
9) Lee, G. H.; Choi, E. B.; Lee, E.; Pak, C. S. Tetrahedron Lett.
1993, 34, 4541.
(
(
(
10) Song, J. J.; Tan, Z. L.; Reeves, J. T.; Gallou, F.; Yee, N. K.;
Senanayake, C. H. Org. Lett. 2005, 7, 2193.
11) Folleas, B.; Marek, I.; Normant, J. F.; Saint-Jalmes, L.
Tetrahedron 2000, 56, 275.
12) Chang, Y.; Cai, C. Tetrahedron Lett. 2005, 46, 3161.
13) Stewart, R.; Teo, K. C. Can. J. Chem. 1980, 58, 2491.
I.; Stammers, D. K. Structure 2000, 8, 1089. (e) Pedersen,
O. S.; Pedersen, E. B. Synthesis 2000, 479. (f) Price, M. L.
P.; Jorgensen, W. L. J. Am. Chem. Soc. 2000, 122, 9455.
(g) Böhm, H. J.; Banner, D.; Bendels, S.; Kansy, M.; Kuhn,
(
(
B.; Müller, K.; Obst-Sander, U.; Stahl, M. ChemBioChem
Synthesis 2010, No. 11, 1899–1904 © Thieme Stuttgart · New York

1
904
Y. Zhao et al.
SPECIAL TOPIC
(
(
14) Isao, K.; Takayuki, H.; Shoji, T.; Masayoshi, M.; Chizu, S.;
Takeshi, T.; Koichi, F. EP 0434297, 1991.
15) Xu, Q.; Zhou, H.; Geng, X. H.; Chen, P. R. Tetrahedron
(16) Shechter, H.; Conrad, F. J. Am. Chem. Soc. 1950, 72, 3371.
(17) Kuwano, R.; Kondo, Y.; Shirahama, T. Org. Lett. 2005, 7,
2973.
2009, 65, 2232.
Synthesis 2010, No. 11, 1899–1904 © Thieme Stuttgart · New York