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The stereochemistry of nitrone-diene cycloadditions. Synthesis of the alkaloids of darlingia darlingiana
Tetrahedron Letters,Vol.27,No.ll,pp Printed in Great Britain
THE STEREOCHEMISTRY
1265-1268,1986
OF NITRONE-DIENE CYCLOADDITIONS. OF DARLINGIA DARLINGIANA
0040-4039/86 $3.00 + .OO 01986 Pergamon Press Ltd.
SYNTHESIS
OF THE ALKALOIDS
J. J. Tufariello and J. M. Puglis of Chemistry, State University of New York at Buffalo Buffalo, New York 14214
Department
The stereochemical outcome of the reactions of cyclic nitrones with (E)-l-phenylThe syntheses of darlinine, epidarlinine, tetra1,3-butadiene has been explored. hydrodarlingianine, and dehydrodarlinine have been accomplished.
Summary:
The stereochemistry
addends
in two parallel
proceed
through
involving frontier
of nitrone
cycloaddition
has been the subject
of several
accepted view of these reactions involves an approach of the 195 Thus, like the Diels-Alder reaction, such processes may planes.
either -exo- or endo-transition
certain
reactions
A generally
recent studies.lW4
electron
molecular
deficient
orbital
over its -exo-counterpart
states.
dipolarophiles
(FMO) theory
by a favorable
Examinations
(e.g. acrylates)
of the transition
suggest that an endo transition secondary
orbital
states
from the perspective
of
state should be favored
involvement. 2y3y6y7
Indeed, the
LUMO
HOMO
reactions
of acyclic
to afford
the adducts
nitrones
with dimethyl maleate
expected
from the a-addition
nitrones to monosubstituted dipolarophiles 10 result in poor stereoselectivity.
do proceed with substantial stereoselectivity 2,336 process; however, additions of such
such as methyl
acrylate,8
a-methylstyrene,'
and
styrene
The possibility cycloaddition vehicles
with which
the cycloaddition major
of E/Z isomerization
suggested
alkaloids
of the starting
that cyclic nitrones,
to explore
incapable
this phenomenon.
of 1-pyrroline (e.g., darlinine
dehydrodarlinine
(5)) derivedfrom
area of northern
Queensland,
l-oxide
acyclic
nitrones
concomitant
of this complication,
Moreover,
with
might be better
we were specifically
interested
in
(1) with certain dienes as a means of synthesizing
(2), epidarlinine
(3), tetrahydrodarlingianine
Darlingia darlingiana, 11,12 Australia.
1265
(4), and
tall trees found in the rain forest
the
1266
, q&G ,’
Ph
Ph
Me
Me 2
3 d
(--&k, I
I
rite
file
4 & The cycloaddition toluene
affords
of l-pyrroline
a stereoisomeric
The adduct 6 displays
91% yield. spectrum,
5 r)
assignable
l-oxide
mixture
(1) with
a characteristically
to the C-6 protons
(E)-1-phenyl-1,3-butadiene
of cycloadducts,
adjacent
6 and 7 (57:43 ratio,
sharp triplet
at 6 3.2 ppm in its pmr
These protons
to the nitrogen.
?L r 0
:H
6
_ 7
Y
81 57
19 43
Ph
rt (10 days), 50% complete: llO", toluene
acetate)
at approximately isomer 7.
demonstrated
appear as two
H
+-Ph-
multiplets
in refluxing respectively),
6 3.0 and 3.5 ppm for the slower eluting
That the isomer distribution
by "taking each pure cycloadduct
obtained
and exposing
reflected
(tic:
silica gel; ethyl
thermodynamic
it to 110".
Ph
factors
was
In each case, the same
ratio of 6 and 7 (i.e. 55:45) was obtained. When the cycloaddition non-equilibrating 81:19 ratio,
conditions
respectively.
to the related
of nitrone
1 with
(room temperature,
(E)-1-phenyl-1,3-butadiene 10 days), adducts
This ratio is similar
cyclic nitrone
to that reported
3,4,5,6_tetrahydropyridine
l-oxide.
was performed
6 and 7 were produced "4
for the addition
under in an
of styrene
Thus, we anticipated
that
in
1267
the major stereoisomer
(i.e. 6) was derived
by an E-mode
of addition,
while
7 was produced -via
exo Ph
endo
Ph 6h an endo-transition
state.
into the respective verted
The structural
Darlingia
into their respective
alkaloid. methiodide
6
7
temperature. darlinine (3).
Nitrogen-oxygen
(2), while
The spectral
authentic
Toward
like treatment
by conversion
of each isomer
this end, both 6 and 7 were independently
salts by treatment
with methyl
Et20
>
Zn HOAc
’
Mel Et20
>
Zn HOAc
> 3 -
in the methiodide
of the methiodide of the synthetic
2 s.
salt derived
salt derived
alkaloids
con-
iodide in ether at room
Mel
bond cleavage
characteristics
were confirmed
from 6 afforded
from 7 afforded
correspond-to
epidarlinine
those of the
alkaloids.13'14
A manganese chloride
assignments
dioxide
induced oxidation
gave dehydrodarlinine
With the knowledge
that diene-nitrone
adducts,
we chose to compare
terminal
alkene.
single adduct
of either darlinine
or epidarlinine
in dry methylene
(5) in 60% yield.
these findings
When nitrone
cycloadditions
proceed
with those obtained
1 was added to 4-phenyl-1-butene
(i.e. 8) was obtained
in 73% yield.
to afford both stereoisomeric
by the cycloaddition in refluxing
That this cycloaddition
toluene,
proceeded
of a related only a through
an
1268
H
6
>
pd/C
1
8
-exo-transition
state was confirmed
with that product contrast,
obtained
hydrogenation
anticipated,4
of 7 afforded
alkene-nitrone
Tetradehydrodarlingianine refluxing cleavage
toluene,
by a positive
spectral
(86%) upon hydrogenation an adduct
cycloadditions
by methiodide
of this adduct
(i.e. 8)
(70%) spectrally
of the exo-adduct 6. in distinct from 8. Thus, as
proceed via -exo-transition states exclusively. by the addition of 6-phenyl-1-hexene to nitrone
(4) was prepared
followed
comparison
(Pd/C; ethanol)
formation
and subsequent
zinc induced
1 in
hydrogenolytic
of the N-O bond.
References
and Notes
1.
(a) Huisgen, (b) Huisgen,
R. J. Org. Chem. 1976, 41, 403; R.; Grashey, R.; Hauck, H.; Seidl, H.
2.
Gree, R.; Carrie,
R.
Tetrahedron
Lett.
3.
Joucla, M.; Gree, D.; Hamelin,
4.
Tufariello,
J.
5.
Leroy, G.; Nguyen, M. T.; Sana, M.
6.
Gree, R.; Tonnard,
7.
Houk, K. N.; Sims, J.; Watts, C. R.; Luskas,
J. J.; Ali, Sk. A.
F.; Carrie,
2043.
1973, 9,
2315.
Lett. 1978, 4647.
Tetrahedron
1978, 34, 2459.
Bull. Chim. Sot. Fr. 1975, 1325. L. J.
J. Am. Chem. Sot. 1973, 95, 7301.
8.
Joucla, M.; Hamelin,
9.
Huisgen,
R.; Grashey,
R.; Seidl, H.; Hauck, H.
Chem. Ber. 1968, 101, 2559.
10.
Huisgen,
R.; Grashey,
R.; Hauck,
Chem. Ber. 1968, 101, 2548.
I. R.; Gillard,
J.
Tetrahedron
Tetrahedron
R.
Chem. Ber. 1968, 101,
1971, 4117.
11.
Bick,
12.
Anderson, B.; Robertson, 1977, 764.
J. Chem. Res.
H.; Seidl, H.
J.; Leow, H. G.; Bick,
13.
Leow, H.
14.
We thank Professor Bick for sending Darlingia alkaloids.
Ph.D. Dissertation,
(S) 1978, 276.
Aust. J. Chem. I. R.; Gillard,
University
of Tasmania
us the spectral
(Received in USA 19 November 1985)
1979, 37_, 2523. J.; Leow, H.
Chem. and Ind. (London)
(Australia), information
1979.
relating
to the
THE STEREOCHEMISTRY
1265-1268,1986
OF NITRONE-DIENE CYCLOADDITIONS. OF DARLINGIA DARLINGIANA
0040-4039/86 $3.00 + .OO 01986 Pergamon Press Ltd.
SYNTHESIS
OF THE ALKALOIDS
J. J. Tufariello and J. M. Puglis of Chemistry, State University of New York at Buffalo Buffalo, New York 14214
Department
The stereochemical outcome of the reactions of cyclic nitrones with (E)-l-phenylThe syntheses of darlinine, epidarlinine, tetra1,3-butadiene has been explored. hydrodarlingianine, and dehydrodarlinine have been accomplished.
Summary:
The stereochemistry
addends
in two parallel
proceed
through
involving frontier
of nitrone
cycloaddition
has been the subject
of several
accepted view of these reactions involves an approach of the 195 Thus, like the Diels-Alder reaction, such processes may planes.
either -exo- or endo-transition
certain
reactions
A generally
recent studies.lW4
electron
molecular
deficient
orbital
over its -exo-counterpart
states.
dipolarophiles
(FMO) theory
by a favorable
Examinations
(e.g. acrylates)
of the transition
suggest that an endo transition secondary
orbital
states
from the perspective
of
state should be favored
involvement. 2y3y6y7
Indeed, the
LUMO
HOMO
reactions
of acyclic
to afford
the adducts
nitrones
with dimethyl maleate
expected
from the a-addition
nitrones to monosubstituted dipolarophiles 10 result in poor stereoselectivity.
do proceed with substantial stereoselectivity 2,336 process; however, additions of such
such as methyl
acrylate,8
a-methylstyrene,'
and
styrene
The possibility cycloaddition vehicles
with which
the cycloaddition major
of E/Z isomerization
suggested
alkaloids
of the starting
that cyclic nitrones,
to explore
incapable
this phenomenon.
of 1-pyrroline (e.g., darlinine
dehydrodarlinine
(5)) derivedfrom
area of northern
Queensland,
l-oxide
acyclic
nitrones
concomitant
of this complication,
Moreover,
with
might be better
we were specifically
interested
in
(1) with certain dienes as a means of synthesizing
(2), epidarlinine
(3), tetrahydrodarlingianine
Darlingia darlingiana, 11,12 Australia.
1265
(4), and
tall trees found in the rain forest
the
1266
, q&G ,’
Ph
Ph
Me
Me 2
3 d
(--&k, I
I
rite
file
4 & The cycloaddition toluene
affords
of l-pyrroline
a stereoisomeric
The adduct 6 displays
91% yield. spectrum,
5 r)
assignable
l-oxide
mixture
(1) with
a characteristically
to the C-6 protons
(E)-1-phenyl-1,3-butadiene
of cycloadducts,
adjacent
6 and 7 (57:43 ratio,
sharp triplet
at 6 3.2 ppm in its pmr
These protons
to the nitrogen.
?L r 0
:H
6
_ 7
Y
81 57
19 43
Ph
rt (10 days), 50% complete: llO", toluene
acetate)
at approximately isomer 7.
demonstrated
appear as two
H
+-Ph-
multiplets
in refluxing respectively),
6 3.0 and 3.5 ppm for the slower eluting
That the isomer distribution
by "taking each pure cycloadduct
obtained
and exposing
reflected
(tic:
silica gel; ethyl
thermodynamic
it to 110".
Ph
factors
was
In each case, the same
ratio of 6 and 7 (i.e. 55:45) was obtained. When the cycloaddition non-equilibrating 81:19 ratio,
conditions
respectively.
to the related
of nitrone
1 with
(room temperature,
(E)-1-phenyl-1,3-butadiene 10 days), adducts
This ratio is similar
cyclic nitrone
to that reported
3,4,5,6_tetrahydropyridine
l-oxide.
was performed
6 and 7 were produced "4
for the addition
under in an
of styrene
Thus, we anticipated
that
in
1267
the major stereoisomer
(i.e. 6) was derived
by an E-mode
of addition,
while
7 was produced -via
exo Ph
endo
Ph 6h an endo-transition
state.
into the respective verted
The structural
Darlingia
into their respective
alkaloid. methiodide
6
7
temperature. darlinine (3).
Nitrogen-oxygen
(2), while
The spectral
authentic
Toward
like treatment
by conversion
of each isomer
this end, both 6 and 7 were independently
salts by treatment
with methyl
Et20
>
Zn HOAc
’
Mel Et20
>
Zn HOAc
> 3 -
in the methiodide
of the methiodide of the synthetic
2 s.
salt derived
salt derived
alkaloids
con-
iodide in ether at room
Mel
bond cleavage
characteristics
were confirmed
from 6 afforded
from 7 afforded
correspond-to
epidarlinine
those of the
alkaloids.13'14
A manganese chloride
assignments
dioxide
induced oxidation
gave dehydrodarlinine
With the knowledge
that diene-nitrone
adducts,
we chose to compare
terminal
alkene.
single adduct
of either darlinine
or epidarlinine
in dry methylene
(5) in 60% yield.
these findings
When nitrone
cycloadditions
proceed
with those obtained
1 was added to 4-phenyl-1-butene
(i.e. 8) was obtained
in 73% yield.
to afford both stereoisomeric
by the cycloaddition in refluxing
That this cycloaddition
toluene,
proceeded
of a related only a through
an
1268
H
6
>
pd/C
1
8
-exo-transition
state was confirmed
with that product contrast,
obtained
hydrogenation
anticipated,4
of 7 afforded
alkene-nitrone
Tetradehydrodarlingianine refluxing cleavage
toluene,
by a positive
spectral
(86%) upon hydrogenation an adduct
cycloadditions
by methiodide
of this adduct
(i.e. 8)
(70%) spectrally
of the exo-adduct 6. in distinct from 8. Thus, as
proceed via -exo-transition states exclusively. by the addition of 6-phenyl-1-hexene to nitrone
(4) was prepared
followed
comparison
(Pd/C; ethanol)
formation
and subsequent
zinc induced
1 in
hydrogenolytic
of the N-O bond.
References
and Notes
1.
(a) Huisgen, (b) Huisgen,
R. J. Org. Chem. 1976, 41, 403; R.; Grashey, R.; Hauck, H.; Seidl, H.
2.
Gree, R.; Carrie,
R.
Tetrahedron
Lett.
3.
Joucla, M.; Gree, D.; Hamelin,
4.
Tufariello,
J.
5.
Leroy, G.; Nguyen, M. T.; Sana, M.
6.
Gree, R.; Tonnard,
7.
Houk, K. N.; Sims, J.; Watts, C. R.; Luskas,
J. J.; Ali, Sk. A.
F.; Carrie,
2043.
1973, 9,
2315.
Lett. 1978, 4647.
Tetrahedron
1978, 34, 2459.
Bull. Chim. Sot. Fr. 1975, 1325. L. J.
J. Am. Chem. Sot. 1973, 95, 7301.
8.
Joucla, M.; Hamelin,
9.
Huisgen,
R.; Grashey,
R.; Seidl, H.; Hauck, H.
Chem. Ber. 1968, 101, 2559.
10.
Huisgen,
R.; Grashey,
R.; Hauck,
Chem. Ber. 1968, 101, 2548.
I. R.; Gillard,
J.
Tetrahedron
Tetrahedron
R.
Chem. Ber. 1968, 101,
1971, 4117.
11.
Bick,
12.
Anderson, B.; Robertson, 1977, 764.
J. Chem. Res.
H.; Seidl, H.
J.; Leow, H. G.; Bick,
13.
Leow, H.
14.
We thank Professor Bick for sending Darlingia alkaloids.
Ph.D. Dissertation,
(S) 1978, 276.
Aust. J. Chem. I. R.; Gillard,
University
of Tasmania
us the spectral
(Received in USA 19 November 1985)
1979, 37_, 2523. J.; Leow, H.
Chem. and Ind. (London)
(Australia), information
1979.
relating
to the