A Convenient Method for the Synthesis of α-Imidostyrenes from Styrenes and Imides via Diphenylstyrylsulfonium Salts

Article abstract of DOI:10.1246/cl.2003.1192

Styrenes having a hydrogen atom at the α-position reacted with diphenyl(trifluoromethanesulfonyloxy)sulfonium triflate (1) to form diphenylstyrylsulfonium triflates 2 that were in turn converted into the corresponding α-imidostyrenes on treatment with sodium or potassium salts of cyclic imides.

Full text of DOI:10.1246/cl.2003.1192

1192
Chemistry Letters Vol.32, No.12 (2003)
A Convenient Method for the Synthesis of ꢀ-Imidostyrenes
from Styrenes and Imides via Diphenylstyrylsulfonium Salts
Hiroyuki Yamanakay;yy and Teruaki Mukaiyamaꢀy;yy
yCenter for Basic Research, The Kitasato Institute, 6-15-5 (TCI), Toshima, Kita-ku, Tokyo 114-0003
yyKitasato Institute for Life Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641
(Received September 11, 2003; CL-030855)
Styrenes having a hydrogen atom at the ꢀ-position reacted
with diphenyl(trifluoromethanesulfonyloxy)sulfonium triflate
(1) to form diphenylstyrylsulfonium triflates 2 that were in turn
converted into the corresponding ꢀ-imidostyrenes on treatment
with sodium or potassium salts of cyclic imides.
Table 1. Reactions of 2aa with metal salts of cyclic imide or
amide compounds
Ph
S
R1R2NM
Ph
R1
(1.1 equiv.)
N
R2
OTf
Cl
Cl
DMSO
Substituted vinylsulfonium salts are frequently used as use-
ful synthetic intermediates that react with various nucleophiles.
Formation of cyclopropanes by the reaction of dimethylvinylsul-
fonium salts with enolates1 or anionic species of active methyl-
ene compounds2 is among the best known examples. Recently,
convenient methods for the syntheses of 2-arylaziridines3 and al-
lylamines4 via diphenylvinylsulfonium salts were reported from
our laboratory.
In this communication, we would like to describe a new
method for the synthesis of ꢀ-imidostyrenes, useful precursors
of vinylamines, by introducing an imido group to the ꢀ-position
of styrenes via diphenylstyrylsulfonium salts.
In the first place, a reaction of isolated [(E)-2-(4-chlorophen-
yl)ethenyl]diphenylsulfonium triflate (2a)3,5 with several cyclic
imide compounds was tried (Table 1, Entries 1–4). Several ꢀ-
imidostyrenes were synthesized smoothly in DMSO6 at room
temperature although the reaction with sodium 1,8-naphthal-
imide proceeded much more slowly than the cases with the other
imides, which was presumably due to its steric effect (Entry 1).
Moreover, isatin, a cyclic amide, gave the similar product in
moderate yield (Entry 5). 4-Chloro-ꢀ-phthalimidostyrene was
obtained in 90% yield by using potassium phthalimide (Entry
4); however, when [(E)-2-(4-chlorophenyl)ethenyl]dimethylsul-
fonium triflate was used instead of 2a, 4-chloro-ꢀ-phthalimido-
styrene was not detected and N-methylphthalimide (58%) was
obtained along with (E)-4-chlorostyryl methyl sulfide (88%).
Next, ꢀ-phthalimidation of several styrenes in one vessel ac-
cording to the present method was examined (Table 2, Entries 1–
4). Styrene and 4-chlorostyrene were converted into the corre-
sponding ꢀ-phthalimidostyrene in high yields without isolating
the intermediate sulfonium salts 2 (Entries 1 and 2). Electron-do-
nating groups in a benzene ring lowered the yield and allowed
several unknown by-products to be obtained (Entries 3 and 4).
Furthermore, N-vinylphthalimide gave the desired 1,1-diphthal-
imidoethylene in moderate yield (Entry 5). In the above reac-
tions, 1 equiv. of potassium phthalimide was used for neutraliz-
ing 1 equiv. of triflic acid generated during the preparation of the
sulfonium salt; therefore, when 1 equiv. of potassium phthal-
imide was used, the reaction did not proceed at all.
2a
R1R2NM
Methodb
Conditions
Yield /%c
36
Entry
O
NaN
A
A
A
B
A
rt, 40 h
rt, 3 h
1
2
O
O
NaN
69
84
90
62
O
O
NaN
rt, 12 h
rt, 12 h
rt, 1 h
3
4
5
O
O
KN
O
O
O
N
Na
aSingle isomer with E-configuration. bMethod A: Imide or
amide (1.1 equiv.) was added to a stirred suspension of so-
dium hydride (1.1 equiv.) in DMSO at rt. After 0.5 h, 2a
was added. Method B: A mixture of 2a and potassium phtha-
c
limide (1.1 equiv.) in DMSO was stirred. Isolated yield.
sulfoxide and triflic anhydride (Tf2O), reacted with styrenes to
form the corresponding diphenylstyrylsulfonium triflate 2. Then,
nucleophilic addition of phthalimide anion, for example, to the
ꢀ-position of 2 gave 4 in which 1,2-prototropic shift took place
to form 5. Subsequent regeneration of a double bond by elimi-
nating diphenyl sulfide produced the ꢀ-phthalimidostyrenes 6.
The behavior of diphenylvinylsulfonium salts shown in the steps
4 to 6 is a unique one and is quite different from that of similar
intermediates, vinylphosphonium salts that undergo the so-
called Schweizer reaction.7
The overall synthetic route with a proposed reaction mech-
anism is shown in Scheme 1. Initially, diphenyl(trifluorometha-
nesulfonyloxy)sulfonium triflate (1), prepared from diphenyl
Thus, an effective and convenient method for the synthesis
of ꢀ-imidostyrenes from styrene derivatives and cyclic imides
was established.
Copyright Ó 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.12 (2003)
1193
Table 2. Reactions of olefins with potassium phthalimide via
diphenylvinylsulfonium salts
Further studies for the scope and limitation of the present
reaction are now in progress.
A typical experimental procedure for the synthesis of ꢀ-imi-
dostyrenes is as follows (Table 2, Entry 1): To a stirred solution
of diphenyl sulfoxide (30.3 mg, 0.15 mmol) in dichloromethane
(0.3 mL) was added triflic anhydride (0.025 mL, 0.15 mmol) un-
der an argon atmosphere at ꢁ78 ꢂC, followed by dropwise addi-
tion of styrene (15.6 mg, 0.15 mmol) in dichloromethane
(0.3 mL) at the same temperature. After 10 min, the reaction
mixture was warmed up to 0 ꢂC, and the solvent was removed
in vacuo. To the residue were added DMSO (0.3 mL) and potas-
sium phthalimide (83.3 mg, 0.45 mmol), and the mixture was
stirred at room temperature for 16 h. The reaction mixture was
quenched with cold water (10 mL), and the organic material
was extracted with ether (10 mL ꢃ 2). The combined organic
layers were dried over anhydrous sodium sulfate, filtrated, and
evaporated. After crude precipitates formed by addition of a
small amount of chloroform were removed by filtration, the fil-
trate was evaporated. The resulting crude products were purified
by preparative TLC to give ꢀ-phthalimidostyrene (32.5 mg,
87%).
O
KN
Ph2SO (1.0 equiv.)
O
O
Tf2O (1.0 equiv.) (3.0 equiv.)
R
N
R
CH2Cl2
DMSO
Temp., Time
−78−0 oC
O
Entry Substrate Conditionsa
Product
Yield /%b
O
N
1
2
3
4
5
rt, 16 h
rt, 3 h
87
86
50
51
48
O
O
N
Cl
Cl
Me
O
O
N
rt, 24 h
rt, 15 h
60 oC, 1 h
Me
O
O
This study was supported in part by the Grant of the 21st
Century COE Program from the Ministry of Education, Culture,
Sports, Science and Technology (MEXT), Japan.
N
t-Bu
t-Bu
O
O
O
O
References and Notes
1
a) K. Takaki and T. Agawa, J. Org. Chem., 42, 3303 (1977).
b) K. Takaki, H. Takahashi, Y. Ohshiro, and T. Agawa, J.
Chem. Soc., Chem. Commun., 1977, 675. c) K. Takaki, K.
Negoro, and T. Agawa, J. Chem. Soc., Perkin Trans. 1,
1979, 1490.
N
N
N
O
O
O
aFor the second step. bIsolated yield.
´
2
a) J. Gosselck, L. Beress, and H. Schenk, Angew. Chem., 78,
606 (1966). b) J. Gosselck, H. Ahlbrecht, F. Dost, H. Schenk,
and G. Schmidt, Tetrahedron Lett., 9, 995 (1968).
J. Matsuo, H. Yamanaka, A. Kawana, and T. Mukaiyama,
Chem. Lett., 32, 392 (2003).
H. Yamanaka, J. Matsuo, A. Kawana, and T. Mukaiyama,
Chem. Lett., 32, 626 (2003).
V. G. Nenajdenko, P. V. Vertelezkij, I. D. Gridnev, N. E.
Shevchenko, and E. S. Balenkova, Tetrahedron, 53, 8173
(1997).
We checked several solvents and found DMSO to be superi-
or over any other solvent. The reaction in CH2Cl2 proceeded
much more slowly.
a) E. E. Schweizer, L. D. Smucker, and R. J. Votral, J. Org.
Chem., 31, 467 (1966). b) D. J. Hart, P. A. Cain, and D. A.
Evans, J. Am. Chem. Soc., 100, 1548 (1978). c) A. I. Meyers,
J. P. Lawson, and D. R. Carver, J. Org. Chem., 46, 3119
(1981). d) G. H. Posner, J. P. Mallamo, and A. Y. Black,
Tetrahedron, 37, 3921 (1981).
SPh2
OTf
OTf
Tf2O
PhtNM
DMSO
Ar
3
4
5
O SPh2
TfO SPh2
CH2Cl2
Ar
H
1
2
SPh2
SPh2
H
H+ transfer
PhtN
Ar
PhtN
Ar
H
+ MOTf
6
7
3
5
4
SPh2
+ Ph2S
PhtN
Ar
O
PhtN
Ar
NPht : N
6
O
Scheme 1.
Published on the web (Advance View) November 27, 2003; DOI 10.1246/cl.2003.1192