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Electroreductive synthesis of 1-(bromobenzyl)-isoquinoline derivatives and its application to cularine synthesis
Tetrahedron Letters, Vo1.22, Printed in Great Britain
No.25,
0040-4059/81/252585-Q&02.00/0 01981 Pergamon Press Ltd.
pp 2585 - 2388, 1981
ELE~TR~REDu~TIvE SYNTHESIS OF I-(BROM~BEN~YL)-ISOQUINOLINE DERIVATIVES AND ITS APPLICATION TO CULARINE SYNTHESIS'
* Tatsuya
Shono,
Tetsuya
Department
Miyamoto,
of Synthetic
Kyoto University,
Electrochemical derivatives useful
reduction
Masamichi
Chemistry,
Yoshida,
of immonium
of several
natural
Faculty
Sakyo, Kyoto
derivatives alkaloids
and Hiroshi
Hamaguchi
of Engineering, 606, Japan
salts in the presence
gave 1-(bromobenzyl)-isoquinoline
in the synthesis
Mizukami,
of bromobenzylbromide
in moderate
as exemplified
yields.
This reaction
in the synthesis
is
of
Cularine. Although of Cularine, synthesis mainly
l-(bromobenzylj-isoquinoline
2
Aporphine,
the bromination
derivatives
Dibenzopyrocoline,
has not necessarily
the reaction
4
Berbine,
been established.
of the benzyl moiety
is rather lack of selectivity
In the present through
3
of immonium
intermediates
and Bisbenzylisoquinoline,
The synthetic
methods
of 1-benzyl-isoquinoline
hitherto
derivatives,
in the synthesi; 6
their
known are and hence
and generality.
study, a new and simple method
electroreduction7
are useful 5
of 1-(bromobenzyl)-isoquinoline
salts [I]~ and bromobenzylbromides
SCE is described.
synthesis
[III]' at - 1.8 V vs.
Br
QQ
6
+
Br
2e
N
[III-J
'R'
R
'R'
R
w% Br
Our new method
CIVI
[III
[II
is highly versatile
as summarized
2585
in Table I.
2306
CH,Br
Me0 Me0 Me0
CD
+
Me0 xx?
3
&H -0Ms
'Me TL
3a: R'=Br, R'=R'=H b: R'=Br,
R'=R3=H
, R’=R’=H
c: R3=Br
1
2
Me0 CH,Br Br
ha: R'= tl, R2= OMe
Me0
b: R'=R2=OMe 4
x3
R2
R2 QJ
c: R'= C&Me,
R'=H
R1
Br
6a: R'=H,
R'=OMe
b: RI = R2 = 011~.
R'
c: R'= CO,Me, R2= H
6
5a: R1=Br,
R2=R3=H
b: R'=Br,
R'=R3=H Me0
c: R3= Br, R'= R2=H Me0
N,H 7a: R=H
R
b: R=OMe ?I3
Br
R
7
Table Immonium
I.
Salts
Reaction
of Immonium
Salts with Bromobenzylbromides.
Bromobenzylbromides
Products
Yields
3a
5a
65
3b
5b
47
3c
5c
48
4a
6a
61
4b
6b
51
4c
6c
60
3a
7a
50
4b
7b
53
(W)
It is noteworthy with
the bromomethyl Furthermore,
that the anions moiety
[II] generated
from immonium
of the bromobenzylbromide
our method
is applicable
salts [I] react selectively
[III].
to indole derivatives
as well
as isoquinoline
derivatives.
A new synthesis
9, 70%
3a
8
of Cularine
could be performed
as depicted
by using this simple method
below.
I
MeGeM?
ieObBr
+e OMe
lol*
4b
14, d, I-Cularine
13 The electroreduction
solution13
12.
Debenzylation
and subsequent
yields
and versatility
(10)7a at - 2.0 V Vs. SCE in the presence
of 12 to a phenolic
Ullmann
the total yield from 10 being Although
salt
(4b) followed by NaBH& reduction
a bromobenzylbromide a product
of an immonium
reaction
14
of the resulting
compound
enamine
(11) afforded
13 in ethanolic hydrochloric
by CuO in pyridine
of
gave d,Z-Cularine
acid
(14),14
52%.
of our new benzylation
of the electrochemical
reaction
reaction
are not always
satisfactory,
make this new synthesis
the simplicity
promising.
Acknowledgement This research
was partly
supported
by a Grant-in-Aid
for Special
Project
Research
(Grant
2388
No. 411109),
which
the authors
gratefully
acknowledged.
References
1) 2)
3)
4)
5)
6)
Electroorganic
Chemistry.
51.
a)
T. Kametani,
b)
H. Iida, H. C. Hsu, and T. Kikuchi,
K. Fukumoto,
a)
A. H. Jackson
and M. Fujihara,
b)
T. Kametani,
a)
T. Kametani
and .I. A. Martin, S. Shibuya,
F. Benington
a)
T. Kametani
b)
C. Tani, S. Takao,
J. Chem. SOC.
BUZZ., 20, 1800 (1972).
Phan.
CC), 1966,
M. Hiiragi,
J. Ckem.
and R. D. Morin,
&em.
ibid., 21, 1001 (1973).
K. Kigasawa,
and K. Ogasawara,
b)
and Notes
SOC.
H. Endo, and E. Oda,
and 0. Kusama,
32, 1050 (1967).
(Cl, 1967,
530.
J. PkarT. Sot. Jpn., 93, 268 (1973).
H. Iida, and K. Sakurai, J. Ckem. Sot. CC), 1971,
a)
T. Kametani,
b)
R. W. Doskotch,
a)
T. Shono, K. Yoshida,
ibid., 1971, 2712.
(Cl, 1967, 2208.
J. Org. C&m.,
and M. Ihara, J. Chem. Sot.
2061.
1024.
A. B. Ray, and J. L. Beal, J. Org. Ckem.. 36, 2409
.I. D. Phillipson,
(1971). 7)
K. Ando, Y. Usui, and H. Hamaguchi,
Tetrahedron Lett., 1978,
4819. b)
T. Shono, Y. Usui, T. Mizutani,
8)
Immonium
salts were prepared
9)
2-Bromo-5-methoxybenzylbromide Other derivatives their bromotoluene
10)
R. Breslow,
11)
The starting
ibid., 21, 3073 (1980).
to the established
(4a) was prepared
method.
according
7
to the reported
of bromobenzylbromides (3a-c, 4b,c) were synthesized 11 by NBS. derivatives
S. Garratt, bromotoluene
L. Kaplan,
and D. LaFollette,
derivatives
4b. T. Heap, T. G. H. Jones, 4c. A. M. Fleifel,
and H. Hamaguchi,
according
were prepared
and R. Robinson,
method.
10
by bromination
of
J. Am. Ckem. SOC.. 90, 4051 (1968) according
to the reported
method.
J. Ckem. Sot.. 1927, 2021.
J. Org. Ckem., 25, 1024 (1960).
12)
A. H. Jackson,
G. W. Stewart,
13)
H. Iida, T. Kikuchi,
14)
S. Ishiwata,
G. A. Charnock,
and J. A. Martin, J. Ckem. Sot., Perkin
Trans 2, 1974, 1911. K. Sakurai,
T. Fujii, N. Miyaji,
1850 (1970).
(Received
in Japan
16 March 1981)
and T. Watanabe,
J. Pkarm. Sot. Jpn., 89, 645 (1969).
Y. Satoh, and K. Itakura,
Ckem. Pkarm. Bull., 18,
No.25,
0040-4059/81/252585-Q&02.00/0 01981 Pergamon Press Ltd.
pp 2585 - 2388, 1981
ELE~TR~REDu~TIvE SYNTHESIS OF I-(BROM~BEN~YL)-ISOQUINOLINE DERIVATIVES AND ITS APPLICATION TO CULARINE SYNTHESIS'
* Tatsuya
Shono,
Tetsuya
Department
Miyamoto,
of Synthetic
Kyoto University,
Electrochemical derivatives useful
reduction
Masamichi
Chemistry,
Yoshida,
of immonium
of several
natural
Faculty
Sakyo, Kyoto
derivatives alkaloids
and Hiroshi
Hamaguchi
of Engineering, 606, Japan
salts in the presence
gave 1-(bromobenzyl)-isoquinoline
in the synthesis
Mizukami,
of bromobenzylbromide
in moderate
as exemplified
yields.
This reaction
in the synthesis
is
of
Cularine. Although of Cularine, synthesis mainly
l-(bromobenzylj-isoquinoline
2
Aporphine,
the bromination
derivatives
Dibenzopyrocoline,
has not necessarily
the reaction
4
Berbine,
been established.
of the benzyl moiety
is rather lack of selectivity
In the present through
3
of immonium
intermediates
and Bisbenzylisoquinoline,
The synthetic
methods
of 1-benzyl-isoquinoline
hitherto
derivatives,
in the synthesi; 6
their
known are and hence
and generality.
study, a new and simple method
electroreduction7
are useful 5
of 1-(bromobenzyl)-isoquinoline
salts [I]~ and bromobenzylbromides
SCE is described.
synthesis
[III]' at - 1.8 V vs.
Br
6
+
Br
2e
N
[III-J
'R'
R
'R'
R
w% Br
Our new method
CIVI
[III
[II
is highly versatile
as summarized
2585
in Table I.
2306
CH,Br
Me0 Me0 Me0
CD
+
Me0 xx?
3
&H -0Ms
'Me TL
3a: R'=Br, R'=R'=H b: R'=Br,
R'=R3=H
, R’=R’=H
c: R3=Br
1
2
Me0 CH,Br Br
ha: R'= tl, R2= OMe
Me0
b: R'=R2=OMe 4
x3
R2
R2 QJ
c: R'= C&Me,
R'=H
R1
Br
6a: R'=H,
R'=OMe
b: RI = R2 = 011~.
R'
c: R'= CO,Me, R2= H
6
5a: R1=Br,
R2=R3=H
b: R'=Br,
R'=R3=H Me0
c: R3= Br, R'= R2=H Me0
N,H 7a: R=H
R
b: R=OMe ?I3
Br
R
7
Table Immonium
I.
Salts
Reaction
of Immonium
Salts with Bromobenzylbromides.
Bromobenzylbromides
Products
Yields
3a
5a
65
3b
5b
47
3c
5c
48
4a
6a
61
4b
6b
51
4c
6c
60
3a
7a
50
4b
7b
53
(W)
It is noteworthy with
the bromomethyl Furthermore,
that the anions moiety
[II] generated
from immonium
of the bromobenzylbromide
our method
is applicable
salts [I] react selectively
[III].
to indole derivatives
as well
as isoquinoline
derivatives.
A new synthesis
9, 70%
3a
8
of Cularine
could be performed
as depicted
by using this simple method
below.
I
MeGeM?
ieObBr
+e OMe
lol*
4b
14, d, I-Cularine
13 The electroreduction
solution13
12.
Debenzylation
and subsequent
yields
and versatility
(10)7a at - 2.0 V Vs. SCE in the presence
of 12 to a phenolic
Ullmann
the total yield from 10 being Although
salt
(4b) followed by NaBH& reduction
a bromobenzylbromide a product
of an immonium
reaction
14
of the resulting
compound
enamine
(11) afforded
13 in ethanolic hydrochloric
by CuO in pyridine
of
gave d,Z-Cularine
acid
(14),14
52%.
of our new benzylation
of the electrochemical
reaction
reaction
are not always
satisfactory,
make this new synthesis
the simplicity
promising.
Acknowledgement This research
was partly
supported
by a Grant-in-Aid
for Special
Project
Research
(Grant
2388
No. 411109),
which
the authors
gratefully
acknowledged.
References
1) 2)
3)
4)
5)
6)
Electroorganic
Chemistry.
51.
a)
T. Kametani,
b)
H. Iida, H. C. Hsu, and T. Kikuchi,
K. Fukumoto,
a)
A. H. Jackson
and M. Fujihara,
b)
T. Kametani,
a)
T. Kametani
and .I. A. Martin, S. Shibuya,
F. Benington
a)
T. Kametani
b)
C. Tani, S. Takao,
J. Chem. SOC.
BUZZ., 20, 1800 (1972).
Phan.
CC), 1966,
M. Hiiragi,
J. Ckem.
and R. D. Morin,
&em.
ibid., 21, 1001 (1973).
K. Kigasawa,
and K. Ogasawara,
b)
and Notes
SOC.
H. Endo, and E. Oda,
and 0. Kusama,
32, 1050 (1967).
(Cl, 1967,
530.
J. PkarT. Sot. Jpn., 93, 268 (1973).
H. Iida, and K. Sakurai, J. Ckem. Sot. CC), 1971,
a)
T. Kametani,
b)
R. W. Doskotch,
a)
T. Shono, K. Yoshida,
ibid., 1971, 2712.
(Cl, 1967, 2208.
J. Org. C&m.,
and M. Ihara, J. Chem. Sot.
2061.
1024.
A. B. Ray, and J. L. Beal, J. Org. Ckem.. 36, 2409
.I. D. Phillipson,
(1971). 7)
K. Ando, Y. Usui, and H. Hamaguchi,
Tetrahedron Lett., 1978,
4819. b)
T. Shono, Y. Usui, T. Mizutani,
8)
Immonium
salts were prepared
9)
2-Bromo-5-methoxybenzylbromide Other derivatives their bromotoluene
10)
R. Breslow,
11)
The starting
ibid., 21, 3073 (1980).
to the established
(4a) was prepared
method.
according
7
to the reported
of bromobenzylbromides (3a-c, 4b,c) were synthesized 11 by NBS. derivatives
S. Garratt, bromotoluene
L. Kaplan,
and D. LaFollette,
derivatives
4b. T. Heap, T. G. H. Jones, 4c. A. M. Fleifel,
and H. Hamaguchi,
according
were prepared
and R. Robinson,
method.
10
by bromination
of
J. Am. Ckem. SOC.. 90, 4051 (1968) according
to the reported
method.
J. Ckem. Sot.. 1927, 2021.
J. Org. Ckem., 25, 1024 (1960).
12)
A. H. Jackson,
G. W. Stewart,
13)
H. Iida, T. Kikuchi,
14)
S. Ishiwata,
G. A. Charnock,
and J. A. Martin, J. Ckem. Sot., Perkin
Trans 2, 1974, 1911. K. Sakurai,
T. Fujii, N. Miyaji,
1850 (1970).
(Received
in Japan
16 March 1981)
and T. Watanabe,
J. Pkarm. Sot. Jpn., 89, 645 (1969).
Y. Satoh, and K. Itakura,
Ckem. Pkarm. Bull., 18,