A convenient method for the synthesis of β,γ-unsaturated amines from alkenes via α,β-unsaturated diphenylsulfonium salts

Article abstract of DOI:10.1246/cl.2003.626

1,1-Disubstituted and trisubstituted alkenes were converted into the corresponding β,γ-unsaturated amines 4 via three steps: the initial formation of α,β-unsaturated diphenylsulfonium triflates 2 from alkenes and diphenyl(trifluoromethanesulfonyloxy)sulfo

Full text of DOI:10.1246/cl.2003.626

6
26
Chemistry Letters Vol.32, No.7 (2003)
A Convenient Method for the Synthesis of ꢀ,ꢁ-Unsaturated Amines
from Alkenes via ꢂ,ꢀ-Unsaturated Diphenylsulfonium Salts
y;yy
y;yy
y;yy ꢀy;yy
and Teruaki Mukaiyama
Center for Basic Research, The Kitasato Institute, 6-15-5 (TCI), Toshima, Kita-ku, Tokyo 114-0003
Hiroyuki Yamanaka,
Jun-ichi Matsuo,
Asahi Kawana,
y
yy
Kitasato Institute for Life Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641
(Received April 15, 2003; CL-030324)
1
,1-Disubstituted and trisubstituted alkenes were converted
Table 1. ꢀ,ꢁ-Unsaturated amines from ꢂ-methylstyrene and
various primary or secondary amines via ꢂ,ꢀ-unsaturated di-
phenylsulfonium salts
into the corresponding ꢀ,ꢁ-unsaturated amines 4 via three
steps: the initial formation of ꢂ,ꢀ-unsaturated diphenylsulfo-
nium triflates 2 from alkenes and diphenyl(trifluoromethanesul-
fonyloxy)sulfonium trifluoromethanesulfonate (1), followed by
double bond migration of 2 to ꢀ,ꢁ-unsaturated sulfonium tri-
flates 3 with primary or secondary amines, and successive
nucleophilic substitution of 3 with these amines.
Ph SO (1.2 equiv.)
Tf O (1.2 equiv.)
2
2
H C
3
1 2
R R NH
NR1R2
CH2Cl2
Solvent
Temp., Time
Ph
Ph
°
−
78–0 C
Entry Amine / equiv.
Solvent Temp., Time Yield /%a
Allyl amines are valuable target products in medicinal
1
chemistry and are also used as versatile synthetic inter-
2
1
2
3
Ph
Ph
NH2 / 5.0
NH2 / 10
CH
none
CH Cl
2
Cl
2
rt, 2 h
rt, 2 h
80
78
84
mediates. Although many methods are available for the pre-
3
paration of allyl alcohols by allylic oxidation of alkenes, only
a few are known for the synthesis of allyl amines from alkenes,
Me
4
as reported in stoichiometric allylic aminations using S- or Se-
5
/ 5.0
NH2
2
2
rt, 24 h
Ph
imido derivatives, and catalytic aminations with hydroxyl-
6
7
amines in the presence of the molybdenum or iron catalyst.
A convenient synthesis of 2-arylaziridines from alkenes and
primary amines via 2-arylethenyl(diphenyl)sulfonium salts was
4
5
t-BuNH2 / 5.0
CH2Cl2
MF
CH Cl
DMF
rt, 12 h
91
82
D
100 C, 5 h
°
PhNH2 / 10
8
recently reported from our laboratory. In the attempted aziridi-
nation of ꢂ-methylstyrene with benzylamine according to our
procedure, 3-benzylamino-2-phenyl-1-propene was obtained in
6
7
i
-
-Pr2NH / 5.0
rt, 12 h
89
81
2
2
Bn2NH / 5.0
100 C, 2 h
°
8
0% yield instead of expected 1-benzyl-2-methyl-2-phenylazir-
idine. This might be attributed to the steric hindrance at ꢀ-posi-
tion of diphenyl(2-phenyl-1-propenyl)sulfonium triflate which
apparently prevented the initial Michael type addition of ben-
zylamine at the ꢀ-position. The above reaction turned out to be
useful for introducing amino functions into alkenes to form
a
Isolated yield.
8
unsaturated amines in moderate to good yields (entries 1-8). 2-
Phenyl-1-butene afforded a mixture of (E)- and (Z)-1-benzyla-
mino-2-phenyl-2-butene (1:1) in 55% combined yield along
with 1-benzyl-2-ethyl-2-phenylaziridine in 25% yield (entry
4). In the case of 2-phenyl-3-methyl-1-butene, consumption of
the corresponding sulfonium salt 2 was incomplete even after
prolonged reaction time or heating, presumably because the
steric hindrance at ꢁ-position of 2 inhibited its smooth double
bond migration (entry 5). 2-Methyl-1-pentene afforded the ex-
pected two regioisomers with no significant regioselectivity (en-
try 7). Trisubstituted alkenes gave the desired amines as well
although the yields were low (entries 9 and 10), which may
be due to the steric repulsion between the intermediate 3 and
the amine. In the cases of aliphatic monosubstituted and 1,2-dis-
ubstituted alkenes, the corresponding ꢀ,ꢁ-unsaturated amines
were not obtained. It seemed that the amount of the key inter-
mediates, sulfonium salts 2, was not sufficient since secondary
carbocations generated from alkenes and 1 were not stable
enough to form the adducts.
ꢀ
,ꢁ-unsaturated amines.
In this communication, we would like to describe a novel
and convenient method for the preparation of ꢀ,ꢁ-unsaturated
amines by the reaction of ꢂ,ꢀ-unsaturated diphenylsulfonium
triflates 2, formed from alkenes and diphenyl(trifluoromethane-
sulfonyloxy)sulfonium trifluoromethanesulfonate (1), with pri-
mary or secondary amines.
Results in Table 1 indicate that ꢂ-methylstyrene was con-
verted into various ꢂ-(aminomethyl)styrenes on treating with
1
yields without accompanying the formation of aziridines. The
reactions with monoalkylamines proceeded smoothly at room
temperature (entries 1-4), while higher temperature was re-
quired in the case with aniline (entry 5). In a similar fashion,
the reactions with secondary amines also provided the corre-
sponding ꢀ,ꢁ-unsaturated tertiary amines in good yields (entries
9
followed by various primary or secondary amines in good
6
and 7).
A proposed reaction mechanism is shown in Scheme 1: the
initial formation of ꢂ,ꢀ-unsaturated diphenylsulfonium triflate
2 by the reaction of an alkene with 1 was supported by H
Next, the amination of various alkenes with benzylamine
was tried in order to study the scope and limitation of the pre-
1
sent reaction (Table 2). 1,1-Disubstituted alkenes gave the ꢀ,ꢁ-
NMR analysis. Thus formed 2 reacted with a primary or second-
Copyright Ó 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.7 (2003)
627
Table 2. ꢀ,ꢁ-Unsaturated amines from various alkenes and
benzylamine via ꢂ,ꢀ-unsaturated diphenylsulfonium salts
R3
R1
OTf
SPh2
a
R2 R3
R1
OTf
Tf O
α
β
2
Ph SO (1.2 equiv.)
Tf O (1.2 equiv.)
2
2
Ph SO
TfO SPh2
R2
R3
R3
R1
2
γ
NHBn
BnNH2
CH2Cl2
R2
R2
1
2
CH Cl
neat or CH Cl
R1
Entry
2
2
2
2
°
−78–0 C
rt, 2 h
OTf
SPh2
R2
Yield /%b
R3
R3
4
5
4
5
NR R
Alkene
Product
R R NH
R2
+ Ph S
2
NHBn
R1
R1
β
γ
1c
2c
3d
79
Ph
Ph
3
4
NHBn
Scheme 1.
82
ꢂ
der an argon atmosphere at ꢁ78 C, followed by dropwise addi-
tion of ꢂ-methylstyrene (59 mg, 0.50 mmol) in dichloromethane
(1 mL) at the same temperature. After stirring for 10 min, the re-
Cl
Cl
NHBn
80e
Ph
Ph
Ph
Ph
ꢂ
action mixture was warmed up to 0 C, and the solvent was re-
NHBn
Me
moved under reduced pressure. A solution of tert-butylamine
(183 mg, 2.50 mmol) in dichloromethane (1 mL) was added to
the mixture and stirred at room temperature for 12 h. The reac-
tion was quenched by adding 0.1 M (1 M = mol dm ) aqueous
sodium hydroxide solution (20 mL), and the organic material
was extracted with dichloromethane. The combined organic
layers were dried over anhydrous sodium sulfate, filtrated, and
concentrated in vacuo. The crude product was purified by pre-
parative TLC to give 3-(tert-butylamino)-2-phenyl-1-propene
4d,f
55g
45
Ph
Ph
Ph
Ph
NHBn
ꢁ
3
5d
NHBn
6h,i
79
NHBn
NHBn
44g
(
86 mg, 91%).
7h,i
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.
34
NHBn
8j
9i
50
45
47
References
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2
3
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Ph
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1 i
0
a
BnNH2 (10 equiv.) was used without any solvent unless
otherwise noted. Isolated yield. BnNH2 (5equiv.) was used
without any solvent. Reaction time of the second step was
45h. The ratio of E:Z was 4.4:1, determined by the NOE
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e
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i
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CH2Cl2 at ꢁ78 C, and then the mixture was warmed to rt
j
4
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6
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ꢂ
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and diphenyl sulfide via double bond migration from 2 to 3
and subsequent nucleophilic substitution with the amine.
Thus, it was noted that a variety of ꢀ,ꢁ-unsaturated amines
were synthesized from alkenes and primary or secondary
amines via the ꢂ,ꢀ-unsaturated diphenylsulfonium salts.
A typical experimental procedure for the synthesis of ꢀ,ꢁ-
unsaturated amines is as follows (Table 1, entry 4): to a solution
of diphenyl sulfoxide (121 mg, 0.60 mmol) in dichloromethane
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7
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(
1 mL) was added triflic anhydride (0.098 mL, 0.60 mmol) un-
Published on the web (Advance View) June 24, 2003; DOI 10.1246/cl.2003.626