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Novel approach to trans-fused carbobicycles
Tetrahedron Letters,Vo1.25,No.47,pp Printed in Great Britain
NOVEL * Henk Hiemstra
Abstract:
of Organic
Achtergracht
The combination reaction with
dimethyl
lactams describe ation
of type
1, = which
in the first
methodology
compounds
2 and 0.
of an unprecedented with
lithium
place
allylic
directed
Speckamp*,
of Amsterdam, The Netherlands.
N-acyliminium
constitutes
ion cyclization
of an imide a novel
nitrogen
approach
to
carbobicycles.
as dipolar
the successful ethoxy
The principal
and W.Nico
University
SN2' substitution
cuprate
can serve
CARBOBICYCLES
Amsterdam,
on the promising
to bicyclic
dimethyl
Deprotonation
Chemistry,
trans-fused
we reported
0040-4039/84 $3.00 + .OO 81984 Perqamon Press Ltd.
J. Moolenaar
129, 1018 WS
of a silicon
functionalized 1
Marinus
and a subsequent
lithium
Recently',
TO TRANS-FUSED
, Wim J. Klaver,
Laboratory Nieuwe
APPROACH
5453-5456,1984
substitution
utility
conjunctive
application
lactams
feature
synthetic
5, which
reagents.
of this novel leads
of this paper reaction
of w-alkoxy We here annul-
to allenic
nitrogen
is the disclosure
of these
latter
compounds
cuprate.
of ethoxy
lactams
z2 using
LDA in THF was virtually
I(CH,),CECCH,SiMe,
1 =
2
n=2
4
n.3
=
2,”
R=CH2Ph
52
R=CH2Ph
; n=2
72
R=CH2Ph
2
R=SiMe
2
R=H
; n-2
72
R-H
R.H
; n=3
7=" R:C02tBu
3
e
5453
complete
5454
in 30 min at -78OC. afforded angular
2
8
stirring amide
led us to assume in formic
acid
group
carbon
bond
nitrogen
trimethylsilyl
Since
was found
11
isomers
Ring closure
Literature
attempted =
to result
, we repeated
protected
stereochemistry
achieved
instead
NaOH)
assume
in formic
10
of the a-allenic
sequence
led to 5z5
allenic
(Na, NH3)
in cleavage
of its enolate
as NMR
for 5a. Upon =
removal
reaction
Alkylation
we again
on the
into tricyclic
reductive
the above
(2% aqueous
for which
was readily
5&.
precedent
and isoindolones 7 , as well
for 30 min 5a was converted
by N-desilylation
as single
isomer. 6
1 h, -780~ -f O°C)
2 (lh, -78oC;
a cis ring junction
7a5 in 97% yield"'. =
followed
iodide
of isobenzofuranones
of the N-benzyl
with
with
in 55% yield 5 as a single
alkylation
evidence
Alkylation
starting
with
2 and 4, -_
(79%) and $5 (57%)
the cis ring
junction
acid
7k 5 (91% ) and 82 5
to give
(vide supra).
(100%).
Since bicycles, provided
82
R-H
82 -
R=C02tBu
lactams
1 and 2 in essence
a general the lactam
ive was realised
entry
group
at -78Oc
to a solution
yield
reaction bicyclic
ability
, furnishing
carbonyl
fast
ensued
category
ring can be transformed
group
12
are derivatives
into the latter
in the following
and its leaving
10
9
way.
enhanced g
5
z5 as a white
of materials
in a useful
The lactam
(89%) and 82 5 (94%).
-78oC;
dimethyl
30 min,
crystalline
-780~
solid.
carbo-
is at hand, This
manner.
nitrogen
by introduction
of 1.5 eq of lithium (90 min,
of trans-fused
object-
was protected
of the t-butoxyWhen
2
cuprate + -4OOC)
Similarly,
was added in ether,
to afford g
gave
a in 75%
g5
in
91% yield. There reaction13. an amide
are several
interesting
points
To the best of our knowledge
(imide)
nitrogen
serves
associated this
as a leaving
with
this novel
is the first group
example
in a cuprate
cuprate in which
allylic
5455
substitution been
found
also
The products chemistry.
are
y-regioselectivity
reactions
1,3-dienes
and thus well
and applications
suited
offers
trans-fused
obtainable
is observed,
of derivatives
methodology
our
from readily
REFERENCES
2.
Complete
functionalized
Scope
1.
.
in similar
Finally,
to angular starting
14
reaction
of a-allenic
for further
a fully
(Diels
in a small
has 15
alcohols
.
Alder)
stereoselective
carbobicycles
w-ethoxy
which
access
numberof
steps
lactams.
are currently
investigated.
AND NOTES: Klaver
H. Hiemstra,
W.J.
Commercially
available
and W.N.
Speckamp,
J.Org.Chem.,
cis-1,2,3,6_tetrahydrophthalimide
is,
1149
(1984).
was the starting
material
for 22 and 22. Benzylation (PhCH2C1, K2C03, acetone) followed 3 and ethanolysis afforded 2,". Reduction (NaBH4,H+)3, by NaBH4 reduction 4 ethanolysis and trimethylsilylation ((Me3Si)2NH) , respectively,gave 2’. -
3a) J.C. Hubert,
J.B.P.A.
Wijnberg
and W.N.
Speckamp,
Tetrahedron,
22, 1437
1975. b) J.B.P.A. 4.
Wijnberg,
T. Nagasaki, 16, 1987
5.
Yields
H.E. Schoemaker
S. Esumi,
N. Ozawa,
and W.N. Y. Kosugi
Speckamp,
are given
IR(CHC13)
2210,
(m, 2H),
for purified
1685, 4.99
(flash
and F. Hamaguchi,
chromatography)
lH), 3.46
1245, 850 cm-';
(d, J=l5
5~15
Hz,
1.20
(t, J-7 Hz, 3H), 0.10
1250, 850 cm-'; 5~3 Hz, 1.23 1970,
(m, 2H),
Hz,
Heterocycles,
products
'H NMR(CDC13)
IH), 4.16
1.68-2.53 (s, 9H).
'H NMR(CDC13)
IH), 3.3-3.7
4.60-4.86
6 7.30
(m, 2H),
which
(m, 9H), 4 (oil):
6 7.30
showed
IR(CHC13)
(m, IlH),
satis-
2
(oil):
(m, 5H),
IH), 3.99
1.42 (t, J=2.5
(br s, lH), 5.90
1.5-2.5
(except
data are:
(d, J-3 Hz,
(m, 2H),
3.78
(br s, lH), 1.60-2.80
(s), 179.4
(s),
125.1
cd), 46.0
(d), 44.1
IR(CHC13)
3450,
(m, 2H),
134-7OC):
(s), 34.1
3210,
4.70
IR(CHC13)
(br s, lH), 5.84
Hz, 2H),
3450,
2210,1700,
(m, 2H), 4.48
1.40
1975,
(m, 2H), 3350,
cd), 124.9
(t, 5.2.5
(t), 28.2
1710 cm-'; 3.86
1780,
(m, IH), 5.72
(t), 25.7
(t), 24.4
1610 cm-';
(m, 2H),
5.05
6 6.1
1.20-2.80 'H NMR
(d,
Hz, 2H), 3220,
13C NMR(CDC13)
(s), 76.0
'H NMR(CDC13)
(br s, lH), 1710,
(m, 9H);
cd), 99.2
5.62-
(d,
(t), 59.5 (t).
(br s, lH),
(m, IlH). (CDCl3)
(m, IH), 4.97
82 (oil):
p (mp 6 8.12
(m, lH), 1.95
10 (oil): IR(CHC13) 3340, (s, 9H), 1.14-3.02 (m, 9H). = -1 1710 cm ; 'H NMR(CDC13) 6 8.0 (br s, IH), 5.60 (m, 3H), 5.02 (br
(s, 3H), 1785,
179 (1978).
(t, 557 Hz, 3H) 0.08 (s, 9H). 72 (mp 150-2“C): IR(CHC13) 3430, -1 1710 cm ; 'H NMR(CDC13) 6 6.96 (br s, lH), 5.50-5.82 (m, 2H),
6 201.9
5.75
2:,
(1981).
for 82, which as crude material was virtually pure), factory spectral and exact mass data. Some selected
-6.04
Ibid.,
1.45
s, IH), 4.92
(br s, lH),
1.90
(s, 3H),
1.45 (s, 9H),
l-1-3.2
(m, 11H).
5456
13C NMR(CDC13) 126.2
cd),
6 173.1
125.8
35.5
Ct.), 31.4
6.
B.M.
Trost
7.
R. Brettle
a.
The magnitude with
(2
X
149.3
and D.P.
(3
q),
coupling
hydrogen
R. Brettle
128.6
(S),
50.4
(s), 38.9
21.3
(91,
20.4
(1977).
constant 5 of the CHOEt
and S.M. Shibib,
cd),
(1975).
I, 2385
is indicative
(d),
(t), 36.9
(t).
97, 7182 ==
J.Chem.Soc.Perkin
of the vicinal
junction:
X
(s), 143.8
(S),
J.Am.Chem.Soc.,
Cummings,
angular
(s), 144.6
(t), 81.9
28.0
t),
and C.H. Miller,
the adjacent
of ring
(s),
cd), 112.3
hydrogen
of the stereochemistry
J.Chem.Soc.Perkin
I, 2912
(1981). 9.
For intramolecular
a)
H. Hiemstra
b)
R. Schmid,
c)
A.D.
SE reactions
and W.N.
Speckamp,
P.L. Huesmann
of propargyl Tetrahedron
a nd W.S.
silanes
see:
Lett.,
Johnson,
24, 1407 (1983) 23 J.Am.Chem.Soc., 102, 5122 =:=
(1980).
10.
11.
Despo,
S.K.
Chiu,
T. Flood
S. Sugasawa
and T. Fujii,
Chem.Abstr.,
zj, 14242b
Details will
of this
be given
and P.E. Peterson,
Chem.Pharm.Bull.,
6, I
Ibid,
587
=_=, 102 5120
(1980).
(1958);
( 1 960).
interesting
transformation
is shown
(an example
below)
in our full paper. Ph
12. 13.
a)
R.E. Zelle
D.L. Flynn, For copper N.
Ono,
mediated
allylic
I. Hamamoto
J.Org.Chem.,
substitution
and A. Kaji,
Tetrahedron,
b) E. Erdik,
and P.A. Grieco,
ji, 641
4f3,
2424
(1983).
reactions:
J.Chem.Soc.Chem.Commun.,
(1984) and references
274
cited
(1984).
in these
papers. 14.
For substitution
of allylic
a) M. Commeryon-Bourgain, Acad.Sci.C, b) c. Decodts, 15a) J-G.
b)
285 r-r' 211 (1977). C. Dressaire and
Duboudin,
284
351 ==I' H. Kleijn,
quaternary
J.F. Normant
B. Jousseaume
Y.
ammonium
Langlois,
Synthesis,
and A. Bonakdar,
22,
340
510
(1979). Acad.Sci.C,
(1977). H.
Westmijzeand
P. Vermeer,
Tetrahedron
Lett.,
1133
(1978)
Recl.Trav.Chim.Pays-Bas,
(1980).
Kleijn, H. Westmijze, J. Meijer and P. Vermeer,
e) D. Djahanbini, (Received
C.R.Hebd.Seances
C.R.Hebd.Seances
c) H. Kleijn, H. Westmijze, J. Meijer and P. Vermeer, d) H.
salts:
and J. Villieras,
in UK
B. Cazes 16
August
and J. Gore', Tetrahedron 1984)
-Ibid., Lett.
I:?, 378 (1983). ___ $2, 203 (1984).
NOVEL * Henk Hiemstra
Abstract:
of Organic
Achtergracht
The combination reaction with
dimethyl
lactams describe ation
of type
1, = which
in the first
methodology
compounds
2 and 0.
of an unprecedented with
lithium
place
allylic
directed
Speckamp*,
of Amsterdam, The Netherlands.
N-acyliminium
constitutes
ion cyclization
of an imide a novel
nitrogen
approach
to
carbobicycles.
as dipolar
the successful ethoxy
The principal
and W.Nico
University
SN2' substitution
cuprate
can serve
CARBOBICYCLES
Amsterdam,
on the promising
to bicyclic
dimethyl
Deprotonation
Chemistry,
trans-fused
we reported
0040-4039/84 $3.00 + .OO 81984 Perqamon Press Ltd.
J. Moolenaar
129, 1018 WS
of a silicon
functionalized 1
Marinus
and a subsequent
lithium
Recently',
TO TRANS-FUSED
, Wim J. Klaver,
Laboratory Nieuwe
APPROACH
5453-5456,1984
substitution
utility
conjunctive
application
lactams
feature
synthetic
5, which
reagents.
of this novel leads
of this paper reaction
of w-alkoxy We here annul-
to allenic
nitrogen
is the disclosure
of these
latter
compounds
cuprate.
of ethoxy
lactams
z2 using
LDA in THF was virtually
I(CH,),CECCH,SiMe,
1 =
2
n=2
4
n.3
=
2,”
R=CH2Ph
52
R=CH2Ph
; n=2
72
R=CH2Ph
2
R=SiMe
2
R=H
; n-2
72
R-H
R.H
; n=3
7=" R:C02tBu
3
e
5453
complete
5454
in 30 min at -78OC. afforded angular
2
8
stirring amide
led us to assume in formic
acid
group
carbon
bond
nitrogen
trimethylsilyl
Since
was found
11
isomers
Ring closure
Literature
attempted =
to result
, we repeated
protected
stereochemistry
achieved
instead
NaOH)
assume
in formic
10
of the a-allenic
sequence
led to 5z5
allenic
(Na, NH3)
in cleavage
of its enolate
as NMR
for 5a. Upon =
removal
reaction
Alkylation
we again
on the
into tricyclic
reductive
the above
(2% aqueous
for which
was readily
5&.
precedent
and isoindolones 7 , as well
for 30 min 5a was converted
by N-desilylation
as single
isomer. 6
1 h, -780~ -f O°C)
2 (lh, -78oC;
a cis ring junction
7a5 in 97% yield"'. =
followed
iodide
of isobenzofuranones
of the N-benzyl
with
with
in 55% yield 5 as a single
alkylation
evidence
Alkylation
starting
with
2 and 4, -_
(79%) and $5 (57%)
the cis ring
junction
acid
7k 5 (91% ) and 82 5
to give
(vide supra).
(100%).
Since bicycles, provided
82
R-H
82 -
R=C02tBu
lactams
1 and 2 in essence
a general the lactam
ive was realised
entry
group
at -78Oc
to a solution
yield
reaction bicyclic
ability
, furnishing
carbonyl
fast
ensued
category
ring can be transformed
group
12
are derivatives
into the latter
in the following
and its leaving
10
9
way.
enhanced g
5
z5 as a white
of materials
in a useful
The lactam
(89%) and 82 5 (94%).
-78oC;
dimethyl
30 min,
crystalline
-780~
solid.
carbo-
is at hand, This
manner.
nitrogen
by introduction
of 1.5 eq of lithium (90 min,
of trans-fused
object-
was protected
of the t-butoxyWhen
2
cuprate + -4OOC)
Similarly,
was added in ether,
to afford g
gave
a in 75%
g5
in
91% yield. There reaction13. an amide
are several
interesting
points
To the best of our knowledge
(imide)
nitrogen
serves
associated this
as a leaving
with
this novel
is the first group
example
in a cuprate
cuprate in which
allylic
5455
substitution been
found
also
The products chemistry.
are
y-regioselectivity
reactions
1,3-dienes
and thus well
and applications
suited
offers
trans-fused
obtainable
is observed,
of derivatives
methodology
our
from readily
REFERENCES
2.
Complete
functionalized
Scope
1.
.
in similar
Finally,
to angular starting
14
reaction
of a-allenic
for further
a fully
(Diels
in a small
has 15
alcohols
.
Alder)
stereoselective
carbobicycles
w-ethoxy
which
access
numberof
steps
lactams.
are currently
investigated.
AND NOTES: Klaver
H. Hiemstra,
W.J.
Commercially
available
and W.N.
Speckamp,
J.Org.Chem.,
cis-1,2,3,6_tetrahydrophthalimide
is,
1149
(1984).
was the starting
material
for 22 and 22. Benzylation (PhCH2C1, K2C03, acetone) followed 3 and ethanolysis afforded 2,". Reduction (NaBH4,H+)3, by NaBH4 reduction 4 ethanolysis and trimethylsilylation ((Me3Si)2NH) , respectively,gave 2’. -
3a) J.C. Hubert,
J.B.P.A.
Wijnberg
and W.N.
Speckamp,
Tetrahedron,
22, 1437
1975. b) J.B.P.A. 4.
Wijnberg,
T. Nagasaki, 16, 1987
5.
Yields
H.E. Schoemaker
S. Esumi,
N. Ozawa,
and W.N. Y. Kosugi
Speckamp,
are given
IR(CHC13)
2210,
(m, 2H),
for purified
1685, 4.99
(flash
and F. Hamaguchi,
chromatography)
lH), 3.46
1245, 850 cm-';
(d, J=l5
5~15
Hz,
1.20
(t, J-7 Hz, 3H), 0.10
1250, 850 cm-'; 5~3 Hz, 1.23 1970,
(m, 2H),
Hz,
Heterocycles,
products
'H NMR(CDC13)
IH), 4.16
1.68-2.53 (s, 9H).
'H NMR(CDC13)
IH), 3.3-3.7
4.60-4.86
6 7.30
(m, 2H),
which
(m, 9H), 4 (oil):
6 7.30
showed
IR(CHC13)
(m, IlH),
satis-
2
(oil):
(m, 5H),
IH), 3.99
1.42 (t, J=2.5
(br s, lH), 5.90
1.5-2.5
(except
data are:
(d, J-3 Hz,
(m, 2H),
3.78
(br s, lH), 1.60-2.80
(s), 179.4
(s),
125.1
cd), 46.0
(d), 44.1
IR(CHC13)
3450,
(m, 2H),
134-7OC):
(s), 34.1
3210,
4.70
IR(CHC13)
(br s, lH), 5.84
Hz, 2H),
3450,
2210,1700,
(m, 2H), 4.48
1.40
1975,
(m, 2H), 3350,
cd), 124.9
(t, 5.2.5
(t), 28.2
1710 cm-'; 3.86
1780,
(m, IH), 5.72
(t), 25.7
(t), 24.4
1610 cm-';
(m, 2H),
5.05
6 6.1
1.20-2.80 'H NMR
(d,
Hz, 2H), 3220,
13C NMR(CDC13)
(s), 76.0
'H NMR(CDC13)
(br s, lH), 1710,
(m, 9H);
cd), 99.2
5.62-
(d,
(t), 59.5 (t).
(br s, lH),
(m, IlH). (CDCl3)
(m, IH), 4.97
82 (oil):
p (mp 6 8.12
(m, lH), 1.95
10 (oil): IR(CHC13) 3340, (s, 9H), 1.14-3.02 (m, 9H). = -1 1710 cm ; 'H NMR(CDC13) 6 8.0 (br s, IH), 5.60 (m, 3H), 5.02 (br
(s, 3H), 1785,
179 (1978).
(t, 557 Hz, 3H) 0.08 (s, 9H). 72 (mp 150-2“C): IR(CHC13) 3430, -1 1710 cm ; 'H NMR(CDC13) 6 6.96 (br s, lH), 5.50-5.82 (m, 2H),
6 201.9
5.75
2:,
(1981).
for 82, which as crude material was virtually pure), factory spectral and exact mass data. Some selected
-6.04
Ibid.,
1.45
s, IH), 4.92
(br s, lH),
1.90
(s, 3H),
1.45 (s, 9H),
l-1-3.2
(m, 11H).
5456
13C NMR(CDC13) 126.2
cd),
6 173.1
125.8
35.5
Ct.), 31.4
6.
B.M.
Trost
7.
R. Brettle
a.
The magnitude with
(2
X
149.3
and D.P.
(3
q),
coupling
hydrogen
R. Brettle
128.6
(S),
50.4
(s), 38.9
21.3
(91,
20.4
(1977).
constant 5 of the CHOEt
and S.M. Shibib,
cd),
(1975).
I, 2385
is indicative
(d),
(t), 36.9
(t).
97, 7182 ==
J.Chem.Soc.Perkin
of the vicinal
junction:
X
(s), 143.8
(S),
J.Am.Chem.Soc.,
Cummings,
angular
(s), 144.6
(t), 81.9
28.0
t),
and C.H. Miller,
the adjacent
of ring
(s),
cd), 112.3
hydrogen
of the stereochemistry
J.Chem.Soc.Perkin
I, 2912
(1981). 9.
For intramolecular
a)
H. Hiemstra
b)
R. Schmid,
c)
A.D.
SE reactions
and W.N.
Speckamp,
P.L. Huesmann
of propargyl Tetrahedron
a nd W.S.
silanes
see:
Lett.,
Johnson,
24, 1407 (1983) 23 J.Am.Chem.Soc., 102, 5122 =:=
(1980).
10.
11.
Despo,
S.K.
Chiu,
T. Flood
S. Sugasawa
and T. Fujii,
Chem.Abstr.,
zj, 14242b
Details will
of this
be given
and P.E. Peterson,
Chem.Pharm.Bull.,
6, I
Ibid,
587
=_=, 102 5120
(1980).
(1958);
( 1 960).
interesting
transformation
is shown
(an example
below)
in our full paper. Ph
12. 13.
a)
R.E. Zelle
D.L. Flynn, For copper N.
Ono,
mediated
allylic
I. Hamamoto
J.Org.Chem.,
substitution
and A. Kaji,
Tetrahedron,
b) E. Erdik,
and P.A. Grieco,
ji, 641
4f3,
2424
(1983).
reactions:
J.Chem.Soc.Chem.Commun.,
(1984) and references
274
cited
(1984).
in these
papers. 14.
For substitution
of allylic
a) M. Commeryon-Bourgain, Acad.Sci.C, b) c. Decodts, 15a) J-G.
b)
285 r-r' 211 (1977). C. Dressaire and
Duboudin,
284
351 ==I' H. Kleijn,
quaternary
J.F. Normant
B. Jousseaume
Y.
ammonium
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