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Concomitant [2,3]-sigmatropic rearrangement of allylic sulfilimines and intramolecular N-alkylation. Synthesis of 2-vinyl substituted cyclic amines
Tetrahedron Letters,Vo1.30,No.35,pp Printed in Great Britain
CONCOMITANT
C2,31-SIGMATROPIC
INTRAMOLECULAR
Roland Department
REARRANGEMENT SYNTHESIS
N-ALKYLATION.
E. Dolle,*
of Medicinal
OF ALLYLIC
OF 2-VINYL
Smith
Kline
Hertfordshire,
SULFILIMINES
SUBSTITUTED
Li' and Antony
Chun-Sing
Chemistry,
Welwyn,
0040-4039/89 $3.00 Pergamon Press plc
4723-4726,1989
CYCLIC
+ .oo
AND AMINES
N. Shaw
& French
Research
Limited,
U.K. AL6 9AR.
SummarY: Allylic phenyl and methyl sulfides bearing a strategically positioned electrophilic center have been shown to undergo concomitant C2,31-sigmatropic rearrangement and intramolecular N-alkylation upon oxidative conversion to allylic sulfilimines and treatment This one-pot transformation leads to the title class of compounds in with aqueous base. good yield.
The development construction research2
of synthetic
of 2-substituted
nitrogen
we communicate
heterocycles.
possessing
an appropriately
at sulfur,
a [2,31-sigmatropic
Subsequent
intramolecular
a 2-vinyl phenyl
substituted
sulfide
appended
2 investigated
Scheme
Treating
stratagem
To test
remains
undergo,
phenyl
upon oxidative
amine
ii-iii)
ii
would
this hypothesis,
conversion
an active
area of
for preparing
that an allylic
cyclization;
iii.
and stereocontrolled
(Scheme
sulfide
I).
then give rise to the allylic
to N-(p-toluenesulfonyl)-2-
II).
ii in three
tributylphosphine
steps
i
from the known
allylic
and N-(phenylthio)succinimide
toluene '(1 h, 25 "C) and sequential
desilylation
4723
and tosylation
alcohol
4b
34a (Scheme
(1.1 equiv.
(standard
i
amination
I
1 was prepared
3 with
amines
to give an allylic
and its one-pot
iii Sulfide
cyclic
group X would
(i.e.,
ring system
(Scheme
the regio-
It was conceived
leaving
N-alkylation
nitrogen
a novel
rearrangement'
1 was constructed
vinylpyrolidine
permitting
and 2,2_disubstituted
and in this Letter
2-functionalized
methodology
II).
each) in
conditions)
4724
gave 1 in 90% overall
yield.5
were
some experimentation.
identified
to a solution bromide3f added. NaOH
after
Optimal
of I in CH2C12
(0.04 equiv.)
The reaction
(3.0 equiv.)
chromatographic
and after
mixture
(1.1 equiv.)
(10 min>
continued
yielded
1-2
was added
hexadecyltributylphosphonium
30 min at 25 "C, triethylphosphite
was stirred
purification
to carry out the key transformation
Thus chloramine-T6"
(0.2 M) containing
and stirring
Scheme
conditions
followed
by the addition
(30 min; 25 "0'.
sulfonamide
(1.5 equiv.)
Extractive
was
of 1 N aqueous
work-up
and
2 (85%).6b
Ii Chloramine-T
OH
3 steps
PTC; (EtO)3P_
SPh TSm
then aq. NaOH
1 NTs
TsN
kPh
-_$A
---cc++ N T.S
I
4
5: FkSPh
6: In situ amination sulfilimine
of the phenylthio-
4/sulfenamide
5 equilibrium
the side of the sulfenamide triethylphosphite the presence A variety
of allylic
entries
(Table).
phenyl
in these
and methyl
2-Vinyl-
aziridine, (entry
permitting
flexible
protecting
groups
alkyl
halides,
tosylates.
Michael
is drawn
formation
of 2,2-disubstituted
quaternary
II).
(entry
center
to the facile
instigates
sulfides8
process (entry
9).
(entries
cyclic
8,9,10).10
amines,
lies on
conditions NaOH
cyclic
(entry
(in
to 2.
N-p-tolylsulfonamides
(entry
31, pyrolidine using
substituted
- which
this
for chloramine-T
5) or N-derivatization
are compatable
sulfide
with
atom
-
with
amination.
rearrangement/cyclization the nitrogen
in
(e.g..
is the range of electrophiles
promoted
and
in the [2,31-sigmatropic
was readily
epoxides
425
cyclization
have been generated
Noteworthy
an allylic
of aqueous
intramolecular
2). azetidine
where
the equilibrium
Addition
furnishing
sulfilimine
institutes
these reaction
engage
of free amines
acceptors,
allylic
Although
is slow under
and 0-mesitylenesulfonylhydroxylamine
attention
1 by chloramine-T
7) ring systems
isolation
other
chloramine-T
in
0-Mesitylenesulfonylhydroxylamine6'9
reactions
2
R=H
5-6 conversion.
catalyst)
cyclization
1,4,5) and piperidine
methodology.
to accelerate
transfer
rearrangement/intramolecular good yield
(Scheme
5,' S-N solvolysis
is required
of the phase
moiety
H
Finally, promoting
is attached
to a
4725
Table. Conversion of Allylic Phenyl and Methyl Sulfides to P-Vinyl Cyclic Amines and N-Derivatives Aminating Reagent a
Sulfide
Entry
m
CAT
TsowSPh
Isolated Yield (%)
Product
85
N
TS
Br==
SPh
Br-
SPh
CAT
60
CAT
30
HO 52b
CAT Tso &SPh
& N Ts
MSH
H
EtOOC+
7oc H
6
I,
CAT
EtOOC+
87d Ts
+-
+sph TsO-)@-~~
SPh
CAT
HO
CAT
80’
439
MSH cBz
IO
CAT
w N Ts
a) CAT = Chloramine-T; MSH = 0-mesityienesulfonylhydroxylamine. b) Optically active sulfide derived from (R)-pantolactone. c) 1:I ciskrans. d) 1O:l cis/trans. e) intermediate allylic sulfonamide isolated (90%) and cyclized with BF,‘EtzO. f) Racemic sulfide derived from geraniol. g) isolated as the N-benzyl carbamate upon reaction with PhCH,OC(O)Cl, NaHC03.
80
4726
REFERENCES
AND NOTES
1.
Smith Kline
2.
Knouzi, N.; Vaultier, references therein.
3.
A) Ash, A.S.F.; b) Ash, A.S.F.; Challenger, F.; Minamikawa. J.; Matsushima, H.; C.R.; Mori, K.;
4.
a) Marshall, J.A.; DeHoff. B.S. J. Orq. Chem. Tetrahedron Lett. 1977, 18. 4475.
5.
All new compounds structure.
6.
a) Chloramine-T hydrate was used as purchased (Aldrich). O-Mesitylenesulfonylhydroxylamine (MSH) was prepared as previously described: Tamura, Y.; Minamikawa, 3.; Somoto, K.; Fujii, S.; Ikeda, M. J. Or-q. Chem. 1973, 38, 1239. b) This represents a general procedure employing chloramine-T as the aminating reagent. The following is a general procedure employing MSH as the aminating reagent: A CH2Cl2 solution of 1 (0.2 M) was treated with MSH (1.1 equiv.) at 0 “C. The solution was stirred (30 min), then Et3N (3.0 equiv.) and (Et013P (1.5 equiv.) were added and the solution was refluxed. Conventional work-up and purification gave the cyclic amine.
7.
a> Natsugari, H.; Whittle, R.R.; Weinreb, S.M. J. Sharpless. K.B.; Hori, T. 3. Or-a. Chem. 1976, 4l,
& French
Postdoctoral M.; Toupet.
Fellow,
1988-1989.
L.; Carrie,
R. Tetrahedron
Lett.
1987, 28.
1757 and
Challenger, F.; Greenwood, 0. J Chem. Sot. 1951. 1877. Challenger, F. J. Chem. Sot 1952 2792 c) Briscoe, P.A.; Duckworth, P.S. J. Chem. So;. 195i, 1755. d) Tamura Y.; Sumoto, K.; Ikeda. M. Tetrahedron Lett. 1972, U3. 4137. e> Tamura, Y.; Minamikawa, J.; Ikeda, M. Tetrahedron. 1975, 1, 3035. f) Johnson, Nakanishi, A. J. Ors. Chem. 1979. 44, 2065.
exhibited
physical
1986, 5l, 863.
and spectroscopic
b) Walker,
properties
K.A.M.
consistant
Am. Chem, Sot. 1984. m.
with their
7867.
b)
176.
a.
The requisite sulfides (Table) were typically derived conversion to phenyl sulfides (with NPTS4b) or methyl with thioacetic acid (Volante, R.P. Tetrahedron Lett. saponification with K2C037MeOH in the presence of MeI) unmasking/generation of the electrophile.
from ailylic alcohols via initial sulfides (modified Mitsunobu 1981, 22, 3119) and then and subsequent
9.
Use of MSH led to analogous results in most cases; however, N-chlorobenzyland N-chloro-t-butylcarbamate were ineffective. In our hands, allylic N-cBz and N-BOC protected amines were not produced upon treatment of the allylic phenyl or methyl sulfides with these N-chlorocarbamates. This observation is in contrast to the reactivity of allylic phenyl selenides: Shea, R.G.; Fitzner, J.N .; Fankhauser, J.E.; Hopkins, P.B. J. Orq. Chem. 1984, 49, 3647.
amino acid esters as exemplified 10. Oxidation of the vinyl appendage affords N-protected the conversion of 7 (entry 7) to 8. Thus a) t-BuMe2SiC1, imid., DMF; b) 03, Sudan red 78, CH2C12, -78 "C then Ph3P. 25 'C; c) NaC102, NaH2P04, -BuOH, (CH312fXHCH3, H20 (Bal. B.S.; Childers, W.E., Jr.; Pinnick, H.W. Tetrahedron, 1981, 3, 2091) then CH2N2; and d) chromatographic isolation of the major isomer 8 (ca. 25% overall yield, structure B confirmed by 1H NMR). Epimerization occurred during isolation/oxidation of the intermediate aldehyde.
10: R=‘BuMe2Si
8: R=‘BuMe2Si
[aI;
= -59”
(c = 0.9, CHQ)
(Received in UK 14
July
1989)
by
CONCOMITANT
C2,31-SIGMATROPIC
INTRAMOLECULAR
Roland Department
REARRANGEMENT SYNTHESIS
N-ALKYLATION.
E. Dolle,*
of Medicinal
OF ALLYLIC
OF 2-VINYL
Smith
Kline
Hertfordshire,
SULFILIMINES
SUBSTITUTED
Li' and Antony
Chun-Sing
Chemistry,
Welwyn,
0040-4039/89 $3.00 Pergamon Press plc
4723-4726,1989
CYCLIC
+ .oo
AND AMINES
N. Shaw
& French
Research
Limited,
U.K. AL6 9AR.
SummarY: Allylic phenyl and methyl sulfides bearing a strategically positioned electrophilic center have been shown to undergo concomitant C2,31-sigmatropic rearrangement and intramolecular N-alkylation upon oxidative conversion to allylic sulfilimines and treatment This one-pot transformation leads to the title class of compounds in with aqueous base. good yield.
The development construction research2
of synthetic
of 2-substituted
nitrogen
we communicate
heterocycles.
possessing
an appropriately
at sulfur,
a [2,31-sigmatropic
Subsequent
intramolecular
a 2-vinyl phenyl
substituted
sulfide
appended
2 investigated
Scheme
Treating
stratagem
To test
remains
undergo,
phenyl
upon oxidative
amine
ii-iii)
ii
would
this hypothesis,
conversion
an active
area of
for preparing
that an allylic
cyclization;
iii.
and stereocontrolled
(Scheme
sulfide
I).
then give rise to the allylic
to N-(p-toluenesulfonyl)-2-
II).
ii in three
tributylphosphine
steps
i
from the known
allylic
and N-(phenylthio)succinimide
toluene '(1 h, 25 "C) and sequential
desilylation
4723
and tosylation
alcohol
4b
34a (Scheme
(1.1 equiv.
(standard
i
amination
I
1 was prepared
3 with
amines
to give an allylic
and its one-pot
iii Sulfide
cyclic
group X would
(i.e.,
ring system
(Scheme
the regio-
It was conceived
leaving
N-alkylation
nitrogen
a novel
rearrangement'
1 was constructed
vinylpyrolidine
permitting
and 2,2_disubstituted
and in this Letter
2-functionalized
methodology
II).
each) in
conditions)
4724
gave 1 in 90% overall
yield.5
were
some experimentation.
identified
to a solution bromide3f added. NaOH
after
Optimal
of I in CH2C12
(0.04 equiv.)
The reaction
(3.0 equiv.)
chromatographic
and after
mixture
(1.1 equiv.)
(10 min>
continued
yielded
1-2
was added
hexadecyltributylphosphonium
30 min at 25 "C, triethylphosphite
was stirred
purification
to carry out the key transformation
Thus chloramine-T6"
(0.2 M) containing
and stirring
Scheme
conditions
followed
by the addition
(30 min; 25 "0'.
sulfonamide
(1.5 equiv.)
Extractive
was
of 1 N aqueous
work-up
and
2 (85%).6b
Ii Chloramine-T
OH
3 steps
PTC; (EtO)3P_
SPh TSm
then aq. NaOH
1 NTs
TsN
kPh
-_$A
---cc++ N T.S
I
4
5: FkSPh
6: In situ amination sulfilimine
of the phenylthio-
4/sulfenamide
5 equilibrium
the side of the sulfenamide triethylphosphite the presence A variety
of allylic
entries
(Table).
phenyl
in these
and methyl
2-Vinyl-
aziridine, (entry
permitting
flexible
protecting
groups
alkyl
halides,
tosylates.
Michael
is drawn
formation
of 2,2-disubstituted
quaternary
II).
(entry
center
to the facile
instigates
sulfides8
process (entry
9).
(entries
cyclic
8,9,10).10
amines,
lies on
conditions NaOH
cyclic
(entry
(in
to 2.
N-p-tolylsulfonamides
(entry
31, pyrolidine using
substituted
- which
this
for chloramine-T
5) or N-derivatization
are compatable
sulfide
with
atom
-
with
amination.
rearrangement/cyclization the nitrogen
in
(e.g..
is the range of electrophiles
promoted
and
in the [2,31-sigmatropic
was readily
epoxides
425
cyclization
have been generated
Noteworthy
an allylic
of aqueous
intramolecular
2). azetidine
where
the equilibrium
Addition
furnishing
sulfilimine
institutes
these reaction
engage
of free amines
acceptors,
allylic
Although
is slow under
and 0-mesitylenesulfonylhydroxylamine
attention
1 by chloramine-T
7) ring systems
isolation
other
chloramine-T
in
0-Mesitylenesulfonylhydroxylamine6'9
reactions
2
R=H
5-6 conversion.
catalyst)
cyclization
1,4,5) and piperidine
methodology.
to accelerate
transfer
rearrangement/intramolecular good yield
(Scheme
5,' S-N solvolysis
is required
of the phase
moiety
H
Finally, promoting
is attached
to a
4725
Table. Conversion of Allylic Phenyl and Methyl Sulfides to P-Vinyl Cyclic Amines and N-Derivatives Aminating Reagent a
Sulfide
Entry
m
CAT
TsowSPh
Isolated Yield (%)
Product
85
N
TS
Br==
SPh
Br-
SPh
CAT
60
CAT
30
HO 52b
CAT Tso &SPh
& N Ts
MSH
H
EtOOC+
7oc H
6
I,
CAT
EtOOC+
87d Ts
+-
+sph TsO-)@-~~
SPh
CAT
HO
CAT
80’
439
MSH cBz
IO
CAT
w N Ts
a) CAT = Chloramine-T; MSH = 0-mesityienesulfonylhydroxylamine. b) Optically active sulfide derived from (R)-pantolactone. c) 1:I ciskrans. d) 1O:l cis/trans. e) intermediate allylic sulfonamide isolated (90%) and cyclized with BF,‘EtzO. f) Racemic sulfide derived from geraniol. g) isolated as the N-benzyl carbamate upon reaction with PhCH,OC(O)Cl, NaHC03.
80
4726
REFERENCES
AND NOTES
1.
Smith Kline
2.
Knouzi, N.; Vaultier, references therein.
3.
A) Ash, A.S.F.; b) Ash, A.S.F.; Challenger, F.; Minamikawa. J.; Matsushima, H.; C.R.; Mori, K.;
4.
a) Marshall, J.A.; DeHoff. B.S. J. Orq. Chem. Tetrahedron Lett. 1977, 18. 4475.
5.
All new compounds structure.
6.
a) Chloramine-T hydrate was used as purchased (Aldrich). O-Mesitylenesulfonylhydroxylamine (MSH) was prepared as previously described: Tamura, Y.; Minamikawa, 3.; Somoto, K.; Fujii, S.; Ikeda, M. J. Or-q. Chem. 1973, 38, 1239. b) This represents a general procedure employing chloramine-T as the aminating reagent. The following is a general procedure employing MSH as the aminating reagent: A CH2Cl2 solution of 1 (0.2 M) was treated with MSH (1.1 equiv.) at 0 “C. The solution was stirred (30 min), then Et3N (3.0 equiv.) and (Et013P (1.5 equiv.) were added and the solution was refluxed. Conventional work-up and purification gave the cyclic amine.
7.
a> Natsugari, H.; Whittle, R.R.; Weinreb, S.M. J. Sharpless. K.B.; Hori, T. 3. Or-a. Chem. 1976, 4l,
& French
Postdoctoral M.; Toupet.
Fellow,
1988-1989.
L.; Carrie,
R. Tetrahedron
Lett.
1987, 28.
1757 and
Challenger, F.; Greenwood, 0. J Chem. Sot. 1951. 1877. Challenger, F. J. Chem. Sot 1952 2792 c) Briscoe, P.A.; Duckworth, P.S. J. Chem. So;. 195i, 1755. d) Tamura Y.; Sumoto, K.; Ikeda. M. Tetrahedron Lett. 1972, U3. 4137. e> Tamura, Y.; Minamikawa, J.; Ikeda, M. Tetrahedron. 1975, 1, 3035. f) Johnson, Nakanishi, A. J. Ors. Chem. 1979. 44, 2065.
exhibited
physical
1986, 5l, 863.
and spectroscopic
b) Walker,
properties
K.A.M.
consistant
Am. Chem, Sot. 1984. m.
with their
7867.
b)
176.
a.
The requisite sulfides (Table) were typically derived conversion to phenyl sulfides (with NPTS4b) or methyl with thioacetic acid (Volante, R.P. Tetrahedron Lett. saponification with K2C037MeOH in the presence of MeI) unmasking/generation of the electrophile.
from ailylic alcohols via initial sulfides (modified Mitsunobu 1981, 22, 3119) and then and subsequent
9.
Use of MSH led to analogous results in most cases; however, N-chlorobenzyland N-chloro-t-butylcarbamate were ineffective. In our hands, allylic N-cBz and N-BOC protected amines were not produced upon treatment of the allylic phenyl or methyl sulfides with these N-chlorocarbamates. This observation is in contrast to the reactivity of allylic phenyl selenides: Shea, R.G.; Fitzner, J.N .; Fankhauser, J.E.; Hopkins, P.B. J. Orq. Chem. 1984, 49, 3647.
amino acid esters as exemplified 10. Oxidation of the vinyl appendage affords N-protected the conversion of 7 (entry 7) to 8. Thus a) t-BuMe2SiC1, imid., DMF; b) 03, Sudan red 78, CH2C12, -78 "C then Ph3P. 25 'C; c) NaC102, NaH2P04, -BuOH, (CH312fXHCH3, H20 (Bal. B.S.; Childers, W.E., Jr.; Pinnick, H.W. Tetrahedron, 1981, 3, 2091) then CH2N2; and d) chromatographic isolation of the major isomer 8 (ca. 25% overall yield, structure B confirmed by 1H NMR). Epimerization occurred during isolation/oxidation of the intermediate aldehyde.
10: R=‘BuMe2Si
8: R=‘BuMe2Si
[aI;
= -59”
(c = 0.9, CHQ)
(Received in UK 14
July
1989)
by