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Radical cyclization reactions. Cyclopropane ring formation by 3-exo-cyclization of 5-phenylthio-3-pentenyl radicals
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TctrahedronLetters,V01.31.N0.4~PP6085-6088,1990 RiteJinGreatBriti
RADICAL CYCLIZATION
REACTIONS. CYCLOPROPANE
3-MO-CYCLIZATION givorad
RING FORMATION BY
OF 5-PHENYLTHIO-3-PENTENYL and
Eekovidx
Radomir
RADICALS
Sai616
Department of Chemistry, Faculty of Science, University of Belgrade, Studentski trg 16, P. 0. Box 550, 11OCU Belgrade, and Institute for Chemistry, Technology and &tallurgy, Belgrade, Yugoslavia
Free radical
Abstract: thermal
decomposition
acids.
When
cyclopropane
of thiohydroxamic
the reaction
was performed
addition/cyclization/elimination cyclopentanecarbonitriles Free radical
the construction inyl radicals are usually
were
displacement
We assumed lopropane
0.8-1.3
to find
3-butenyl
considered
as a
than as a method for I.-II ring. Cyclopropylcarb-
in 1,2-group migrati.on and radicals. 2,3,5-B Cyclopro-
homolytic
of 3-pentenyl
be achieved
conditions,
by a free radicals. 9
by halomethyl
radicals
by an efficient
1 to the cyc-
quenching
of the
radicals
radical
a reaction
mination
(kf=
2
than could
1.3
for quenching (kq>
kf).
of the phenylthio
mination
group
cyclopropane
Free radical
lo8 set -1 at 25'C),11
radicals
Since
> 1.6 x lo7 set-' be a gcod
x
at 25'C,12
propagation
3 as final
2 having
it was estimated
(k,) adjacent
step
reaction
it was necessary
a rate that
constant
to a radical
we wanted
center
to check
in the radical
cyclopropane
type radicals
2 possessed
ring
higher
the rate of eliwould
be
if this eli-
chain
reaction
and
product.
2
1
tenyl
an
and the corresponding
ring was rather
type
under
that. 3-exo-cyclization
ring opening
afford
of acrylonitrile,
Interconversion carbocyclic
prepared,
2 could
by
2. In order to favour 3-ea-cyclization (kc= 15 x lo4 set -' at 25'C) and suppress reversible opening of the cyclo-
propylcarbinyl
higher
place
as intermediates
with
only
took
in 3-butenylcobaloximes
derivatives
cyclopropylcarbinyl
than
membered
observed
in equilibrium
pane derivatives radical
radical
cf a three
were
was accomplished
obtained.
of cyclopropane
3-butenyl/cyclopropylcarbinyl
closure
of 6-phenylthio-4-hexencic
in the presence
process
were
formaticn
ring esters
2 formation
a phenylthio 6085
was accomplished group,
as a good
when
3-pen-
radical
lea-
6086
ving
in
group,
xamic
esters
the
of
5-position.
2-vinylcyclopropane
on, od
A,
be
intercepted,
Scheme
ition
to A,
but
of in
pent.anecarbonitriles Scheme
1.
and
Table
other
hand, thus
4 under
presence
of
5 were 15
obtained
the
in
4,
obtained
generating excess
50 -
soluti-
yields
radicals
5-heptenyl
aame experimental
in
43 -60%
type
thiohydro-
toluene
of
65% yields
(Meth-
L could
by an intermolecular
closure,
a five-fold
of
boiling in
3-pentenyl
ring
olefins,
esters
the
2 were
cyclopropane
radicophilic
By decomposition Method
On the
before
deccmposition
acids
derivatives
1. )t3
the
by thermal
Thus,
6-phenylthio-4-hexenoic
type
add14 radicals.
conditions
aa in
acrylonitrile,cyclo(Method
(see
B)
1.).
SSPh
Scheme By performing
the
olefins
the
derwent
intramolecular
Table
intermediary
Decomposition
1.
acids Starting esters -4a -4a -4b -4b -4c -4c
c) d)
of
esters
4 without
5-phenylthio-3-pentenyl 3-exo-cyclixation of
radicals
with
thiohydroxamic
concomitant
esters
of
electron 8
deficient
(Scheme
expulsion
2.) of
unthe
6-phenylthio-4-hexenoic
4. Products
R‘
Method
PhCH2
H
A
ia
PhCH2
H
B
R
PhCH2 PhCH2 E’ClOH21 n-ClOH21
CH3 CH3 H H
Iaolatedb vielda 32
and in
(47)
6a
33
(50jd
A
5b
25
(43)
B
6b
40
(52)
A
SC -6c
30
(60)
32
(63)
B
GCC
%
Thermaldecompoaition of 4 in refluxing toluene. Thermal decomposition of 3 in refluxing toluene in the presence of excess acrylonitrile. Prepared according to the Barton procedure (ref. 16). Reaction products were isolated on silica gel column, using petroleumetheriacetone by IR, NMRand mass spectra. 99 : 1 as eluent and characterized Yields of reaction products were also determined by CC. Taken from reference 17.
Method A: Method B: a) b)
a
decomposition
1.
of
6087
phenylthio propane or
derivatives
tertiary
propane but
2 did
indicating
ring
not
on the
supported
sition.
not
that
does
depends
and is
forming
a cyclopropane
change
Since
radicals
rate
were
reaction
of
the
the
(kc)
the
group of
intermedia-
to
the
radical
in
cyclo-
secondary
as
intermediary
phenylthio
of
primary,
leading of
of
3-exo-cyclizat.ion
The yields
involved
nucleophilicity
conformation
presence of
2.
whether i
intramolecular on the
appropriate
by the the
the
depend
ring
appreciably
5-phenylthio-3-pentenyl
thus
tes,
thus
radical,
cy-clo-
species, radicals
the
2,
allylic
3-pentenyl
poradi-
type
SSPh + Ce
. L CN
+4
N
I
R’
- PhS’
Ph
10 -
6
SCheMe 2. cals
6 is
carbinyl takes
Much lower radicals
place
reasons
the
results
cn
cals, our
before
expulsion
yields
of
the
which
ving
to
were
addition
in of
addition
of
than
rate
yl
type
the
phenylthio
from
(kf)
derivatives
the
cyclcpropylreaction
and that
2 were
not
high.
for
of
the 18
present
3-exo-cyclizations, and
radipaper,
support
2-vinylcyclopropane
precursors,
intermediates
could this
Newcomb’s
2,2-dimethyl-5-cyano-4-pentenyl
preparation
similar
of
reversible
radical,
3-exo-cyclisations.
radical
carbanion
opening competing
involving
concerted
de-
an intramolecu-
elimination
of
a lea-
19
However,
the
the
ring the
of
the
the
the
intramolecular
t.he vinylcyclopropanes five-fold
of
that of
during
obtained
of
group.
performed
rate
cyclopropane
concerning
In addition lar
the
4-exo-cyclizations
appeared
findings
rivative-s
than
we believe
2,
the
5, presence
excess
of
of the
addition
was completely excess
radicophilic
5-phenylthio-3-pentenyl
radicals
of
3-exo-cyclization,and -10 by intermolecular
of
reaction
of
suppressed acrylonitrile olefins,
radicals
the i
to
therefore addition
the
e,
leading
reactions B).
rate
intermolecular
of olefins
formation radicophilic
By using was higher of
to
were
(Methcd these the
to
radicals
when the
5-heptenolefins
a
6088
and their
subsequent
described
in our previous
cyclization
to Method
8, in addition
lopropane
derivatives
paper.l7
to Z-vinylcyclopentanecarbonitriles By decomposition
of esters
to vinylcyclopentanecarbonitrile
-5a were obtained
&,
6 was
4, according 2-vinylcyc-
in 3% yield.
REFEREMCES 1. J. W. Wilt, in Free Radicals, Vol. 1. Ed. by J. K. Kochi, John Wiley, New York. 1972. Chaoter 8. J.-M. Surzur; in Reactive Intermediates, Vol. 2. Ed. by R. Abramovich, Plenum Press, New York, 1982, Chapter 3. 2. L. K. Montgomery and J. W. Matt, J. Am. Chem. Sot., 89, 3050 (1967). 3. T. A. Halgren, M. E. H. Howden, M. E. Medof and J. D. Roberts, J. Am. Chem.. Sot., 89, 3051 (1967). 4. P. C. Wong an?i D. Griller, J. Org. Chem., 5, 2327 (1981). 5. P. Dowd and S. -Ch. Choi, J. Am. Chem. Sot., 109, 3493 (1987); Tetrahed E, 9, 77 (1989). 6. A. L. J. Beckwith and D. M. O'Shea, Tetrahedron Letters, 2, 4525 (1986 ). Letters, 11, 4529 (1986). 7. G. Stork and R. Mook, Jr., Tetrahedron 8. B. Giese, N. Heinrich, H. Horler, W. Koch, H. Schwarz, Chem. Ber., 119, 3528 (1986). T. Corker, M. D. Johnson, J. Chem. Sot., Perkin Trans., I, 9. :;5B:f;i2:: 10. A. Effio, D. Griller, K, U. Ingold, A. L. J. Beckwith and A. K. Serelis, J. Am. Chem. Sot., 102, 1734 (1980); C. Chatgiliologu, K. U. Ingold, J. L. J. Johnston, J. LuC. Scaiano, J. Am. Chem. Sot., laj, 7739 (1981); sztyk, D. D. M. Wayner, A. N. Abeywickreyma, A. L. J. Beckwith, J. C. Scaiano and K. U. Ingold, J. Am. Chem. Sot., 107, 4594 (1986). 11. B. Maillard, D. Forrest and K. U. Ingold, J. Am. Chem. Sot., s, 7024 (1976). 12. T. E. Booth, J. L. Greene, Jr., and P. B. Shevlin, J. Am. Chem. Sot., 98, 951 (1976). Thiohydroxamic esters 4 were procedur,e. Method A. 13. Typical experimental prepared in situ without isolation (ref. 16.). To the mixture of-O.87 g (5.9 mM) of N-hydroxy-4-methylthiazole-2(3H)-thione, 0.062 g (0.3 mM) of dimethylaminopyridine and 0.47 g (6 mM) of pyridine in ether (30 ml), a solution of acyl chloride (5.7 mM) was slowly added. When the reaction was completed (1 h), the solvent was removed and the esters were used without purification. The oily residue containing ester 4 (about 5.6 mM) was dissolved in toluene (20 ml) and added dropwise to stirred refluxing After the addition was completoluene (30 ml), in an inert atmosphere. ted, the reaction mixture was heated to reflux during 45 min. The solvent was then removed under reduced pressure and the crude reaction products were purified by chromatography on silica gel column (petroleumether/ace5a was isolated (0.29 g, 32% yield) tone 99 : 1). 2-Benzylvinylcyclopropane as a colorless oil. IR (neat): 3060,130$o, 2920, 2840, 1640, 1605, 1495, 1480, 1465, 1440, 1030, 740, 700 cm . H-NMR (1): 0.50-0.70 (m, 2H1, 0.75-1.50 im, 2H), 2.50-2.65 (m, 2H1, 4.70-5.60 (m, 3H), 7.20 (s, 5H). MS: 158 (M ) 143, 129, 115, 104, 91 (loo%,, 79, 65, 51. Method B. Reaction of thiohydroxamic esters 4 with a five molar excess of acrylonitrile in toluene solution, were performedunder the same experimental conditions as applied in Method A. See also references14 and 17. 14. N. SaiEid and 2. Cekovic, Tetrahedron, 46, 3627 (1990). Letters, 21, 5893 (1986). 15. !I Cekovic a;d A. N. SaiEid , Tetrahedron and S. 2. Zard, Tetrahed16. D. H. R. Barton, D. Bridon, I. Fernandez-Picot, 2733 (1987); D. H. R. Barton, D. Bridon and S. 2. Zard, Tetrapan, 2, hedron, 43, 5307 (19871. and i. Cekovic; Tetrahedron Letters, 2, 4203 (1990). 17. R. N. Saci 18. S. -u. Park, T. R. Varick and M. Newcomb, Tetrahedron Letters, 2, 2975 (1990). and 2. Cekovic, unpublished results. 19. R. Matovic, R. N. SalEi (Received inUK 29 August 1990)
TctrahedronLetters,V01.31.N0.4~PP6085-6088,1990 RiteJinGreatBriti
RADICAL CYCLIZATION
REACTIONS. CYCLOPROPANE
3-MO-CYCLIZATION givorad
RING FORMATION BY
OF 5-PHENYLTHIO-3-PENTENYL and
Eekovidx
Radomir
RADICALS
Sai616
Department of Chemistry, Faculty of Science, University of Belgrade, Studentski trg 16, P. 0. Box 550, 11OCU Belgrade, and Institute for Chemistry, Technology and &tallurgy, Belgrade, Yugoslavia
Free radical
Abstract: thermal
decomposition
acids.
When
cyclopropane
of thiohydroxamic
the reaction
was performed
addition/cyclization/elimination cyclopentanecarbonitriles Free radical
the construction inyl radicals are usually
were
displacement
We assumed lopropane
0.8-1.3
to find
3-butenyl
considered
as a
than as a method for I.-II ring. Cyclopropylcarb-
in 1,2-group migrati.on and radicals. 2,3,5-B Cyclopro-
homolytic
of 3-pentenyl
be achieved
conditions,
by a free radicals. 9
by halomethyl
radicals
by an efficient
1 to the cyc-
quenching
of the
radicals
radical
a reaction
mination
(kf=
2
than could
1.3
for quenching (kq>
kf).
of the phenylthio
mination
group
cyclopropane
Free radical
lo8 set -1 at 25'C),11
radicals
Since
> 1.6 x lo7 set-' be a gcod
x
at 25'C,12
propagation
3 as final
2 having
it was estimated
(k,) adjacent
step
reaction
it was necessary
a rate that
constant
to a radical
we wanted
center
to check
in the radical
cyclopropane
type radicals
2 possessed
ring
higher
the rate of eliwould
be
if this eli-
chain
reaction
and
product.
2
1
tenyl
an
and the corresponding
ring was rather
type
under
that. 3-exo-cyclization
ring opening
afford
of acrylonitrile,
Interconversion carbocyclic
prepared,
2 could
by
2. In order to favour 3-ea-cyclization (kc= 15 x lo4 set -' at 25'C) and suppress reversible opening of the cyclo-
propylcarbinyl
higher
place
as intermediates
with
only
took
in 3-butenylcobaloximes
derivatives
cyclopropylcarbinyl
than
membered
observed
in equilibrium
pane derivatives radical
radical
cf a three
were
was accomplished
obtained.
of cyclopropane
3-butenyl/cyclopropylcarbinyl
closure
of 6-phenylthio-4-hexencic
in the presence
process
were
formaticn
ring esters
2 formation
a phenylthio 6085
was accomplished group,
as a good
when
3-pen-
radical
lea-
6086
ving
in
group,
xamic
esters
the
of
5-position.
2-vinylcyclopropane
on, od
A,
be
intercepted,
Scheme
ition
to A,
but
of in
pent.anecarbonitriles Scheme
1.
and
Table
other
hand, thus
4 under
presence
of
5 were 15
obtained
the
in
4,
obtained
generating excess
50 -
soluti-
yields
radicals
5-heptenyl
aame experimental
in
43 -60%
type
thiohydro-
toluene
of
65% yields
(Meth-
L could
by an intermolecular
closure,
a five-fold
of
boiling in
3-pentenyl
ring
olefins,
esters
the
2 were
cyclopropane
radicophilic
By decomposition Method
On the
before
deccmposition
acids
derivatives
1. )t3
the
by thermal
Thus,
6-phenylthio-4-hexenoic
type
add14 radicals.
conditions
aa in
acrylonitrile,cyclo(Method
(see
B)
1.).
SSPh
Scheme By performing
the
olefins
the
derwent
intramolecular
Table
intermediary
Decomposition
1.
acids Starting esters -4a -4a -4b -4b -4c -4c
c) d)
of
esters
4 without
5-phenylthio-3-pentenyl 3-exo-cyclixation of
radicals
with
thiohydroxamic
concomitant
esters
of
electron 8
deficient
(Scheme
expulsion
2.) of
unthe
6-phenylthio-4-hexenoic
4. Products
R‘
Method
PhCH2
H
A
ia
PhCH2
H
B
R
PhCH2 PhCH2 E’ClOH21 n-ClOH21
CH3 CH3 H H
Iaolatedb vielda 32
and in
(47)
6a
33
(50jd
A
5b
25
(43)
B
6b
40
(52)
A
SC -6c
30
(60)
32
(63)
B
GCC
%
Thermaldecompoaition of 4 in refluxing toluene. Thermal decomposition of 3 in refluxing toluene in the presence of excess acrylonitrile. Prepared according to the Barton procedure (ref. 16). Reaction products were isolated on silica gel column, using petroleumetheriacetone by IR, NMRand mass spectra. 99 : 1 as eluent and characterized Yields of reaction products were also determined by CC. Taken from reference 17.
Method A: Method B: a) b)
a
decomposition
1.
of
6087
phenylthio propane or
derivatives
tertiary
propane but
2 did
indicating
ring
not
on the
supported
sition.
not
that
does
depends
and is
forming
a cyclopropane
change
Since
radicals
rate
were
reaction
of
the
the
(kc)
the
group of
intermedia-
to
the
radical
in
cyclo-
secondary
as
intermediary
phenylthio
of
primary,
leading of
of
3-exo-cyclizat.ion
The yields
involved
nucleophilicity
conformation
presence of
2.
whether i
intramolecular on the
appropriate
by the the
the
depend
ring
appreciably
5-phenylthio-3-pentenyl
thus
tes,
thus
radical,
cy-clo-
species, radicals
the
2,
allylic
3-pentenyl
poradi-
type
SSPh + Ce
. L CN
+4
N
I
R’
- PhS’
Ph
10 -
6
SCheMe 2. cals
6 is
carbinyl takes
Much lower radicals
place
reasons
the
results
cn
cals, our
before
expulsion
yields
of
the
which
ving
to
were
addition
in of
addition
of
than
rate
yl
type
the
phenylthio
from
(kf)
derivatives
the
cyclcpropylreaction
and that
2 were
not
high.
for
of
the 18
present
3-exo-cyclizations, and
radipaper,
support
2-vinylcyclopropane
precursors,
intermediates
could this
Newcomb’s
2,2-dimethyl-5-cyano-4-pentenyl
preparation
similar
of
reversible
radical,
3-exo-cyclisations.
radical
carbanion
opening competing
involving
concerted
de-
an intramolecu-
elimination
of
a lea-
19
However,
the
the
ring the
of
the
the
the
intramolecular
t.he vinylcyclopropanes five-fold
of
that of
during
obtained
of
group.
performed
rate
cyclopropane
concerning
In addition lar
the
4-exo-cyclizations
appeared
findings
rivative-s
than
we believe
2,
the
5, presence
excess
of
of the
addition
was completely excess
radicophilic
5-phenylthio-3-pentenyl
radicals
of
3-exo-cyclization,and -10 by intermolecular
of
reaction
of
suppressed acrylonitrile olefins,
radicals
the i
to
therefore addition
the
e,
leading
reactions B).
rate
intermolecular
of olefins
formation radicophilic
By using was higher of
to
were
(Methcd these the
to
radicals
when the
5-heptenolefins
a
6088
and their
subsequent
described
in our previous
cyclization
to Method
8, in addition
lopropane
derivatives
paper.l7
to Z-vinylcyclopentanecarbonitriles By decomposition
of esters
to vinylcyclopentanecarbonitrile
-5a were obtained
&,
6 was
4, according 2-vinylcyc-
in 3% yield.
REFEREMCES 1. J. W. Wilt, in Free Radicals, Vol. 1. Ed. by J. K. Kochi, John Wiley, New York. 1972. Chaoter 8. J.-M. Surzur; in Reactive Intermediates, Vol. 2. Ed. by R. Abramovich, Plenum Press, New York, 1982, Chapter 3. 2. L. K. Montgomery and J. W. Matt, J. Am. Chem. Sot., 89, 3050 (1967). 3. T. A. Halgren, M. E. H. Howden, M. E. Medof and J. D. Roberts, J. Am. Chem.. Sot., 89, 3051 (1967). 4. P. C. Wong an?i D. Griller, J. Org. Chem., 5, 2327 (1981). 5. P. Dowd and S. -Ch. Choi, J. Am. Chem. Sot., 109, 3493 (1987); Tetrahed E, 9, 77 (1989). 6. A. L. J. Beckwith and D. M. O'Shea, Tetrahedron Letters, 2, 4525 (1986 ). Letters, 11, 4529 (1986). 7. G. Stork and R. Mook, Jr., Tetrahedron 8. B. Giese, N. Heinrich, H. Horler, W. Koch, H. Schwarz, Chem. Ber., 119, 3528 (1986). T. Corker, M. D. Johnson, J. Chem. Sot., Perkin Trans., I, 9. :;5B:f;i2:: 10. A. Effio, D. Griller, K, U. Ingold, A. L. J. Beckwith and A. K. Serelis, J. Am. Chem. Sot., 102, 1734 (1980); C. Chatgiliologu, K. U. Ingold, J. L. J. Johnston, J. LuC. Scaiano, J. Am. Chem. Sot., laj, 7739 (1981); sztyk, D. D. M. Wayner, A. N. Abeywickreyma, A. L. J. Beckwith, J. C. Scaiano and K. U. Ingold, J. Am. Chem. Sot., 107, 4594 (1986). 11. B. Maillard, D. Forrest and K. U. Ingold, J. Am. Chem. Sot., s, 7024 (1976). 12. T. E. Booth, J. L. Greene, Jr., and P. B. Shevlin, J. Am. Chem. Sot., 98, 951 (1976). Thiohydroxamic esters 4 were procedur,e. Method A. 13. Typical experimental prepared in situ without isolation (ref. 16.). To the mixture of-O.87 g (5.9 mM) of N-hydroxy-4-methylthiazole-2(3H)-thione, 0.062 g (0.3 mM) of dimethylaminopyridine and 0.47 g (6 mM) of pyridine in ether (30 ml), a solution of acyl chloride (5.7 mM) was slowly added. When the reaction was completed (1 h), the solvent was removed and the esters were used without purification. The oily residue containing ester 4 (about 5.6 mM) was dissolved in toluene (20 ml) and added dropwise to stirred refluxing After the addition was completoluene (30 ml), in an inert atmosphere. ted, the reaction mixture was heated to reflux during 45 min. The solvent was then removed under reduced pressure and the crude reaction products were purified by chromatography on silica gel column (petroleumether/ace5a was isolated (0.29 g, 32% yield) tone 99 : 1). 2-Benzylvinylcyclopropane as a colorless oil. IR (neat): 3060,130$o, 2920, 2840, 1640, 1605, 1495, 1480, 1465, 1440, 1030, 740, 700 cm . H-NMR (1): 0.50-0.70 (m, 2H1, 0.75-1.50 im, 2H), 2.50-2.65 (m, 2H1, 4.70-5.60 (m, 3H), 7.20 (s, 5H). MS: 158 (M ) 143, 129, 115, 104, 91 (loo%,, 79, 65, 51. Method B. Reaction of thiohydroxamic esters 4 with a five molar excess of acrylonitrile in toluene solution, were performedunder the same experimental conditions as applied in Method A. See also references14 and 17. 14. N. SaiEid and 2. Cekovic, Tetrahedron, 46, 3627 (1990). Letters, 21, 5893 (1986). 15. !I Cekovic a;d A. N. SaiEid , Tetrahedron and S. 2. Zard, Tetrahed16. D. H. R. Barton, D. Bridon, I. Fernandez-Picot, 2733 (1987); D. H. R. Barton, D. Bridon and S. 2. Zard, Tetrapan, 2, hedron, 43, 5307 (19871. and i. Cekovic; Tetrahedron Letters, 2, 4203 (1990). 17. R. N. Saci 18. S. -u. Park, T. R. Varick and M. Newcomb, Tetrahedron Letters, 2, 2975 (1990). and 2. Cekovic, unpublished results. 19. R. Matovic, R. N. SalEi (Received inUK 29 August 1990)