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Intramolecular cycloadditions of oxazoline N-oxides
0040-4039/92 $5.00 + .oO Pergamon Press Lid
Tekahedmn Letters. Vol. 33. No. 17, pp. 2353~2356,1992 Printed in Great Britain
Intramolecular
Cycloadditions
Masato Kobayakawa
Laboratoire
of oxazoline
N-oxides
and Yves Langlois*
de Synthkse des Substances Naturelles Assccii
BPt. 410 Universite de Paris-Sud
au CNRS - ICMO -
91405 Orsay Cedex France
: Various 2-alkenyl oxazoline N-oxides 4 gave rise via a regio and stereoselective
Abstract
[2+3] cycloaddition
to tricyclic
compounds
6 and/or Z, precursors
of functionalized
cycle
alkanones.
In the last few years, the various [2+3] cycloaddition valuable
tool in natural
reactions,
oxazoline
compounds
products
N-oxides,
synthesis’.
isomerisation
of the oxaziridine
with trialkyl orthoesters the corresponding
intermcdiates2-4
toward the use of oxazolines
received
dipoles seemed
or by direct condensation
nitrile oxide-olefin cycloaddition
can be considered
cycloadditions
interest
as a
which can be used in these oxazolines
These
followed
by
of a D-hydroxylaminoalcohol reactivity
when compared
as equivalents
with
of nitrile oxides.
(INOC) are well known7-‘, nothing has been
of oxazoline
in various cycloadditions
increasing
to be very promising.
of the corresponding
(scheme 1) showed increasing
nitrones5. Moreover these compounds
Although the intramolecular
nitrones,
either by oxidation
or amidoacetals5-6
reported about the intramolecular
results concerning
Among the possible
a new class of cyclic
which can be prepared
reactions
N-oxides.
As a part of a program
directed
lo, we disclose in the present paper our preliminary
the achiral version of this reaction,
-u
X=OR,NR,
Scheme 1 Thus 2-alkenyl oxazolines dihydro bromides.
oxazole
Lwere prepared from the commercialy
1 by deprotonation
Oxidation
with MCPBA
with butyllithium
followed
gave the corresponding
available 4,4,2
by alkylation”
oxaziridinooxazolidines
- trimethyl - 4,5 -
with various
alkenyl
2 in high yields12.
2354
These compounds
were in turn smoothly
isomerized
over silica gel2 and gave rise to the anticipated
oxazoline iv-oxides 4 (scheme 2). However this isomerization
was always followed by partial hydrolysis (_r
IO %) of the oxazohne N-oxide moiety giving rise to hydroxylamine After several unsucessful toiuene to give cycloadducts
2
purifications,
esters 2 (Table 1).
the crude mixture of 3 and 5 was directly heated in THF or
fi and/or 2 (Table 2. Scheme 2).
1) BuLi - THF h
2) RBr
Scheme 2 These
results
intramolecular membered g
deserve
cycloaddition
some
comments.
were regioselective
In the cases
of compounds
and gave rise exclusively
ring adducts 6 (entries l-6). Whereas compound
as the major adduct (entry 7). For the monosubstituted
4a. 4b and & (n = 1) to the formation
olefin h
(n = 1 ; R1 = R2 = H) cycloaddition
occured both in refluxing THF and refluxing toluene to give & (entries 1 - 2). Repeating on a mixture of E and Z isomers of & afforded
of five
&i (n = 2 ; R’ = R2 = H) afforded compound
a mixture of two isomeric
these conditions
adducts in the same ratio
(90: IO). altough the more forcing condition (refluxing toluene), gave the better yield (entry 4)13. Finally, it is worthy of note that the cycloaddition
took place even with a trisubstituted
6). The resulting adduct b (n = 1 ; R’ = R2 = Me) underwent sterically, congested cyclopentanone
spontaneous
hydrolysis,
derivative 8 when a trace of water was present.
olefin (entry
leading to the less
2355
R Br
z
3
Yield %
Yield %
Ratio
4&I
a:n=l
R’=R*=H
62
89
86: 14
b:n=l
R’=Me:R*=H
76
97
90: 10
62
98
88: 12
64
88
88: 12
c:n=
1 R’=R*=Mc
d:n=2
Rt=R’=H
Table 1. Preparation of oxazoline derivatives 2,z and 4
Entry
SIarting
Solvent
Time
Temp.
material
WI
@,)
66
4
110
1
4+5 1
a
THF
2
8,
Toluene
3
b
THF
66
4
8,
Toluene
110
5
II
I,
4O(US)
6
c
II
110
7
d
6
7
8
85 69
-
_
5
19
-
-
1.5
62(b)
_
34
-
_
35
-
53
16
49
-
16 2.5
110
Yield (W) (a)
10
a : overall yields from 3 b:mixtureoftwoisomers&R’=Me;R2=H
and R’=H;R2=Meratio:90:10
Table 2. Cycloadditions
In a preliminary
experiment,
hydrolysis
of oxazoline N-oxides 4_
and hydrogenolysis
of the oxazolidinoisoxazolidino
were studied on the major isomer of adduct @J This sequence of reactions can be performed process and gave rise to the cyclopentanone data than the compound relative configurations
previously
as a one pot
derivative 9 (47%) (Scheme 3) which showed the same spectral
described
for this compound
spectrum of its precursor a.
rings
by Curran’4. This correlation
and corroborate
the configurations
allowed the attribution deduced
of the
from the ‘HNMR
2356
H2,Pd-C(lO%) EtOH, HCl. H 2O (0.5 (2: 1). 20°C, 21 h
&J major Scheme 3 Further
studies concerning
the enantioselective
reaction in synthesis are in development Acknowledgements
References
I.
2.
and
version of this cycloaddition
in our laboratory.
: We thank RhBne Poulenc Ag-rochimie and CNRS for a financial support.
notes
Torsell. K.B.G., Nitrile oxides, nitrones and nitronares in organic synthesis, Novel strategies in synthesis, Organic nitm chemistry series, H. Feuer Ed. ; VCH Publishers, New-York, 1988. Keana, J.F.W. ; Lee, T.D. 1. Am. Chem. Sot. 1975,z , 1273- 1274.
3. 4.
Guyot, M. ; Dvolaitzki, M., J. Chem. Res. (S). 1977, 132-133.
5.
Ashbum, S.P., Coates. R.M. J. Org. Chem., 1984, Q, 3127-3133.
6.
Ashbum. S.P., Coa~cs, R.M. J. Org. Chem., 19X5, a,
I.
Kozikowski, A.P. Act. Chem. Res. 1984, u, 410-416.
8. 9. 10. 11.
12. 13. II.
and the use of this
Hendrickson, J.B. ; Pearson, D.A. Tetrahedron Len. 1983, 4657-4660.
Dehaen, W.; Hassner, A., J. Org. Chem. 1991, s,
3076-3081.
896-900 and references there in.
For a review conccming the intramolecular [2 + 31 cycloadditions, see : Oppolzer. W. Angew. Chem. Int. Ed. 1977, a, 10-23. For the use of 2-alkenyloxazolines in Diels Alder reaction see : Kouklovsky, C. ; Pouilhes, A. ; Langlois, Y., J. Am. Chem. Sot. 1990, 112, 6672-6679. For reviews about oxazolines, see : a) Lutomski, K.A. ; Meyers, A.]., Asymmetric synthesis, Morisson, J.D. Ed; Academic Press ; New-York 1984. Vol. 3, Chapter 3, 213-274. b) Maryanoff, B.E. Chemistry of Heterocyclic compounds, Turchi, I. Ed ; J. Wiley and Sons ; New York, 1986 : vol. 45, 963-1017. ‘H N.M.R., s ctra of oxaziridinooxazolidines 1 showed a caracteristic AB signal (J = 10 Hz) for the two protons at C- p” Cycloaddition of oxazoline N-oxide &has also been performed the use of this technic with nitrile oxides, see : Armstrong, S.K. ; Tetrahedron Lett. 1991, x, 4171-4174. Curran D.P 1. Am. Chcm. Sot.. 1983,105, 5826-5833.
(Received in France 10 February
1992)
Tekahedmn Letters. Vol. 33. No. 17, pp. 2353~2356,1992 Printed in Great Britain
Intramolecular
Cycloadditions
Masato Kobayakawa
Laboratoire
of oxazoline
N-oxides
and Yves Langlois*
de Synthkse des Substances Naturelles Assccii
BPt. 410 Universite de Paris-Sud
au CNRS - ICMO -
91405 Orsay Cedex France
: Various 2-alkenyl oxazoline N-oxides 4 gave rise via a regio and stereoselective
Abstract
[2+3] cycloaddition
to tricyclic
compounds
6 and/or Z, precursors
of functionalized
cycle
alkanones.
In the last few years, the various [2+3] cycloaddition valuable
tool in natural
reactions,
oxazoline
compounds
products
N-oxides,
synthesis’.
isomerisation
of the oxaziridine
with trialkyl orthoesters the corresponding
intermcdiates2-4
toward the use of oxazolines
received
dipoles seemed
or by direct condensation
nitrile oxide-olefin cycloaddition
can be considered
cycloadditions
interest
as a
which can be used in these oxazolines
These
followed
by
of a D-hydroxylaminoalcohol reactivity
when compared
as equivalents
with
of nitrile oxides.
(INOC) are well known7-‘, nothing has been
of oxazoline
in various cycloadditions
increasing
to be very promising.
of the corresponding
(scheme 1) showed increasing
nitrones5. Moreover these compounds
Although the intramolecular
nitrones,
either by oxidation
or amidoacetals5-6
reported about the intramolecular
results concerning
Among the possible
a new class of cyclic
which can be prepared
reactions
N-oxides.
As a part of a program
directed
lo, we disclose in the present paper our preliminary
the achiral version of this reaction,
-u
X=OR,NR,
Scheme 1 Thus 2-alkenyl oxazolines dihydro bromides.
oxazole
Lwere prepared from the commercialy
1 by deprotonation
Oxidation
with MCPBA
with butyllithium
followed
gave the corresponding
available 4,4,2
by alkylation”
oxaziridinooxazolidines
- trimethyl - 4,5 -
with various
alkenyl
2 in high yields12.
2354
These compounds
were in turn smoothly
isomerized
over silica gel2 and gave rise to the anticipated
oxazoline iv-oxides 4 (scheme 2). However this isomerization
was always followed by partial hydrolysis (_r
IO %) of the oxazohne N-oxide moiety giving rise to hydroxylamine After several unsucessful toiuene to give cycloadducts
2
purifications,
esters 2 (Table 1).
the crude mixture of 3 and 5 was directly heated in THF or
fi and/or 2 (Table 2. Scheme 2).
1) BuLi - THF h
2) RBr
Scheme 2 These
results
intramolecular membered g
deserve
cycloaddition
some
comments.
were regioselective
In the cases
of compounds
and gave rise exclusively
ring adducts 6 (entries l-6). Whereas compound
as the major adduct (entry 7). For the monosubstituted
4a. 4b and & (n = 1) to the formation
olefin h
(n = 1 ; R1 = R2 = H) cycloaddition
occured both in refluxing THF and refluxing toluene to give & (entries 1 - 2). Repeating on a mixture of E and Z isomers of & afforded
of five
&i (n = 2 ; R’ = R2 = H) afforded compound
a mixture of two isomeric
these conditions
adducts in the same ratio
(90: IO). altough the more forcing condition (refluxing toluene), gave the better yield (entry 4)13. Finally, it is worthy of note that the cycloaddition
took place even with a trisubstituted
6). The resulting adduct b (n = 1 ; R’ = R2 = Me) underwent sterically, congested cyclopentanone
spontaneous
hydrolysis,
derivative 8 when a trace of water was present.
olefin (entry
leading to the less
2355
R Br
z
3
Yield %
Yield %
Ratio
4&I
a:n=l
R’=R*=H
62
89
86: 14
b:n=l
R’=Me:R*=H
76
97
90: 10
62
98
88: 12
64
88
88: 12
c:n=
1 R’=R*=Mc
d:n=2
Rt=R’=H
Table 1. Preparation of oxazoline derivatives 2,z and 4
Entry
SIarting
Solvent
Time
Temp.
material
WI
@,)
66
4
110
1
4+5 1
a
THF
2
8,
Toluene
3
b
THF
66
4
8,
Toluene
110
5
II
I,
4O(US)
6
c
II
110
7
d
6
7
8
85 69
-
_
5
19
-
-
1.5
62(b)
_
34
-
_
35
-
53
16
49
-
16 2.5
110
Yield (W) (a)
10
a : overall yields from 3 b:mixtureoftwoisomers&R’=Me;R2=H
and R’=H;R2=Meratio:90:10
Table 2. Cycloadditions
In a preliminary
experiment,
hydrolysis
of oxazoline N-oxides 4_
and hydrogenolysis
of the oxazolidinoisoxazolidino
were studied on the major isomer of adduct @J This sequence of reactions can be performed process and gave rise to the cyclopentanone data than the compound relative configurations
previously
as a one pot
derivative 9 (47%) (Scheme 3) which showed the same spectral
described
for this compound
spectrum of its precursor a.
rings
by Curran’4. This correlation
and corroborate
the configurations
allowed the attribution deduced
of the
from the ‘HNMR
2356
H2,Pd-C(lO%) EtOH, HCl. H 2O (0.5 (2: 1). 20°C, 21 h
&J major Scheme 3 Further
studies concerning
the enantioselective
reaction in synthesis are in development Acknowledgements
References
I.
2.
and
version of this cycloaddition
in our laboratory.
: We thank RhBne Poulenc Ag-rochimie and CNRS for a financial support.
notes
Torsell. K.B.G., Nitrile oxides, nitrones and nitronares in organic synthesis, Novel strategies in synthesis, Organic nitm chemistry series, H. Feuer Ed. ; VCH Publishers, New-York, 1988. Keana, J.F.W. ; Lee, T.D. 1. Am. Chem. Sot. 1975,z , 1273- 1274.
3. 4.
Guyot, M. ; Dvolaitzki, M., J. Chem. Res. (S). 1977, 132-133.
5.
Ashbum, S.P., Coates. R.M. J. Org. Chem., 1984, Q, 3127-3133.
6.
Ashbum. S.P., Coa~cs, R.M. J. Org. Chem., 19X5, a,
I.
Kozikowski, A.P. Act. Chem. Res. 1984, u, 410-416.
8. 9. 10. 11.
12. 13. II.
and the use of this
Hendrickson, J.B. ; Pearson, D.A. Tetrahedron Len. 1983, 4657-4660.
Dehaen, W.; Hassner, A., J. Org. Chem. 1991, s,
3076-3081.
896-900 and references there in.
For a review conccming the intramolecular [2 + 31 cycloadditions, see : Oppolzer. W. Angew. Chem. Int. Ed. 1977, a, 10-23. For the use of 2-alkenyloxazolines in Diels Alder reaction see : Kouklovsky, C. ; Pouilhes, A. ; Langlois, Y., J. Am. Chem. Sot. 1990, 112, 6672-6679. For reviews about oxazolines, see : a) Lutomski, K.A. ; Meyers, A.]., Asymmetric synthesis, Morisson, J.D. Ed; Academic Press ; New-York 1984. Vol. 3, Chapter 3, 213-274. b) Maryanoff, B.E. Chemistry of Heterocyclic compounds, Turchi, I. Ed ; J. Wiley and Sons ; New York, 1986 : vol. 45, 963-1017. ‘H N.M.R., s ctra of oxaziridinooxazolidines 1 showed a caracteristic AB signal (J = 10 Hz) for the two protons at C- p” Cycloaddition of oxazoline N-oxide &has also been performed the use of this technic with nitrile oxides, see : Armstrong, S.K. ; Tetrahedron Lett. 1991, x, 4171-4174. Curran D.P 1. Am. Chcm. Sot.. 1983,105, 5826-5833.
(Received in France 10 February
1992)