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Dehydrogenative sulfenylation of cyclohexanones
Tetrahedron Letters No. 19, pp 1667 - 1670, 1978. @ PergaxnonPress Ltd. Printed in Great Britain.
DEHYDROGENATIVE
m40-4039/78/0501-1667.
SULFENYLATION
p!o2.00/0.
OF CYCLOHEXANONES
Barry M. Trost and James H. Rigby Department of Chemistry University of Wisconsin-Madison Madison, Wisconsin 53706
(Received in IJSA27 December 1977; received in UK for publication 23 March 1978) The sulfenylation of applications
of carbonyl
for the resultant
The use of disulfides aprotic
conditions
because
in alcohol
in methanolic
methoxide
underwent
triggered the
to be restricted
the ability
and modification',
to strong bases under back to the parent
to cleave cyclobutanones
by sulfenylation
a,a-bis-sulfenylatedcyclobutanone
intermediate
As a result of this study, we examined
of norbornanone.
but not fragmentation--a
elaboration
to reduce cL-thiocarbonyl compounds
fragmentation3. inertness
as a result of the diversity
in structural
thought
in which the reversibly-formed
and determined
sulfenylation
We reported
attention
compounds
is normally
of the known ability
solvents2.
nucleophilically
cycloalkanones
has attracted
a-thiocarbonyl
for such reactions
by thiolates
suffers
compounds
reaction
other
On the other hand, cycloheptanone
which
suggests
the feasibility
of alkoxide
0 )
PhSSPh NaOCH3,
undergo
solvents
a remarkably
forms the subject
as a potential
mild aromatization
of this letter.
to phenolsmakesthis Table 1 and eq
reaction
+
phs&SPh
CH30H
56% bases in alcohol
&Ph
1 method
for the direct
accompanying
sulfenylation
sulfenylation
The fact that few methods
of special
1 of ketones.
Cyclohexanoru
to give o-phenylthiophenols
are available
to convert
which
cyclohexanones
interest4.
1 summarize the examples of this new dehydrogenation
procedure.
The major
Eq 1
1668
No. 19
by-product verified
TABLE 1.
observed
by 'H and
is the bis-sulfenylated 13
C nmr spectroscopy
Dehydrogenative
Entry
Sulfenylation
phenol.
and, in some cases, comparison
4-t-butylcyclohexanone
2
cyclohexanone
group was
with data of known samples5.
% Yield
Product OH
1
of the phenylthio
of Cyclohexanonesa
Time (hr)
Ketone
The ortho position
OH
72
40
3
tetralone
4
3-isopropylcyclohexanone
18
5
2-methylcyclohexanone
25
6
&
192
120
(a) A typical procedure involved refluxing a mixture and 6 mmol of sodium methoxide in 15 ml of methanol. (e) Mp 73-77.5".
of 1 mmol of ketone, 4 mmol of diphenyl disulfide (c) See ref 5a. (d) See ref 5b. (b) Mp 73-4".
Only one alkyl group may be present at an alpha position. led to a 4:3 mixture
of mono- and bissulfenylated
ketones,
For example,
but no phenol.
2,6-dimethylcyclohexanone
A 2,2-dialkylcycohexanone
Eo 2
does not aromatize aromatization.
with dealkylation.
Diketone
5 undergoes
On the other hand, dehydrogenative
secosulfenylation
sulfenylation
unaccompanied
of cyclohexanones
by
is normally
much
No. 19
1669
h
(b) R = PhS
PhS faster than secosulfenylation Control
experiments
under these conditions intermediate
verify
in agreement
is noteworthy
long reaction since normally
A possible
with earlier
6
related
to the products
observations6.
ketones were isolated
times required monounsaturated
rationalization
C02CH3
(see Table 1, entry 6).
that the phenols
mono- and bissulfenylated
extraordinarily
analogs.
of cyclobutanones
(a) R = H
R
PhS
do not undergo
In the case of tetralone,
and shown to convert
in this case compared systems aromatize
sulfenylation
(eq 3) invokes a Favorskii-like
to product.
to the saturated
more rapidly
the The
cyclohexanones
than their saturated
reaction'
which requires
the
O0 SPh
7
_
8 Eq 3
O0
R&m_ qy (a) R = H
9
(b) R = PhS ability
to form the bissulfenylated
This rationale generation
enolate
nicelyaccommodatesall
of the equivalent
7 (or its enol) as a precursor
of our observations
of 7 (i.e. 10) requires II
especially
to the zwitterion
the tetralone
loss of aromaticity.
8.
case since the
Support for this inter-
so
c S
10 __ pretation
derives
11 __
from the conversion
which can be envisioned 2-enones
Q
by treating
to involve
of cyclopentanone
to 2-phenylthiocyclopent-2-enone
the enol forms related
a-dialkylsulfonium
ethylenedithiocyclohexanone
C02R
C02R
11 with base __
cyclohexanones 10
to _ 7 - I 9,the obtention
with sulfenimides',
of 2-arylthiocyclohex.
and the aromatization
--in the last case a Favorskii-like
of
process was also invoked
1670
No. 19
This reaction
provides
group for further
elaboration
the parent phenols
Acknowledgment. Health
access
to ortho substituted
provides
great opportunities.
and thus would constitute
Science
The flexibility
Desulfurization
one of the mildest
We wish to thank the National
for their generous
phenols.
methods
Foundation
of the phenylthio
also provides
entry to
for this transformation.
and the National
Institutes
of
support of our programs.
References 1.
B. M. Trost, T. N. Salzmann, and K. Hiroi, J. Amer. Chem. Sot., & 4487 (1976); D. Seebach and M. Teschner, Chem. Ber., 109, 1601 (1976). Also see T. Kumamoto, S. Kobayashi, and T. Mukaiyama, Bull. Chem. Sot. Japan, $5, 866 (1972). For a review see B. M. Trost, Accounts Chem. Res., submitted for publication,
2.
M. Oki, W. Funakoshi, Funakoshi, ibid., =, 44
3.
B. M. Trost and J. H. Rigby, J. Org. Chem., 41, 3217 (1976).
4.
M. S. Kablaoni, J. Org. Chem., a, 2126 (1974); H. Seeboth and B. Burnowski, @, 700, 50 (1966); D. A. Shirley and W. L. Dean, J. Amer. Chem. Sot., 77, 6077 (1955); W. von E. DoeriFand F. M. Beringer, ibid., 2, 2221 (1949); E. Beckman and H. Eickelberg, Chem. Ber., 2, 418 (1896).
5.
(a) G. E. Hilbert and T. B. Johnson, J. Amer. Chem. Sot., U. S. Pat. 3,188,352; Chem. Abstr., 63,
6.
T. Fujisawa, M. Yamamoto, and G. Tsuchihashi, 3. Org. Chem., 38, 687 (1973).
7.
F. G. Bordwell,
Accounts
8.
H. J. Monteiro,
J. Org. Chem., 42, 2324 (1977).
9.
T. Mukaiyama,
10.
s. Takano,
and A. Nakamura, 832 (1971).
T. Adachi,
S. Yamada,
Bull. Chem. Sot. Japan, 44, 828 (1971); M. Oki and W.
Synthesis,
2,
1526 (1929);
(b) W. Reifschneider,
624 (1972); T. Fujisawa
and T. Kojima,
Chem. Res., 3, 281 (1970).
and T. Kumamoto,
K. Tamigawa,
Bull. Chem. Sot. Japan, 44, 3155 (1971).
S. Hatakeyawa,
and K. Ogasawara,
Heterocycles,
4, 953 (1976).
DEHYDROGENATIVE
m40-4039/78/0501-1667.
SULFENYLATION
p!o2.00/0.
OF CYCLOHEXANONES
Barry M. Trost and James H. Rigby Department of Chemistry University of Wisconsin-Madison Madison, Wisconsin 53706
(Received in IJSA27 December 1977; received in UK for publication 23 March 1978) The sulfenylation of applications
of carbonyl
for the resultant
The use of disulfides aprotic
conditions
because
in alcohol
in methanolic
methoxide
underwent
triggered the
to be restricted
the ability
and modification',
to strong bases under back to the parent
to cleave cyclobutanones
by sulfenylation
a,a-bis-sulfenylatedcyclobutanone
intermediate
As a result of this study, we examined
of norbornanone.
but not fragmentation--a
elaboration
to reduce cL-thiocarbonyl compounds
fragmentation3. inertness
as a result of the diversity
in structural
thought
in which the reversibly-formed
and determined
sulfenylation
We reported
attention
compounds
is normally
of the known ability
solvents2.
nucleophilically
cycloalkanones
has attracted
a-thiocarbonyl
for such reactions
by thiolates
suffers
compounds
reaction
other
On the other hand, cycloheptanone
which
suggests
the feasibility
of alkoxide
0 )
PhSSPh NaOCH3,
undergo
solvents
a remarkably
forms the subject
as a potential
mild aromatization
of this letter.
to phenolsmakesthis Table 1 and eq
reaction
+
phs&SPh
CH30H
56% bases in alcohol
&Ph
1 method
for the direct
accompanying
sulfenylation
sulfenylation
The fact that few methods
of special
1 of ketones.
Cyclohexanoru
to give o-phenylthiophenols
are available
to convert
which
cyclohexanones
interest4.
1 summarize the examples of this new dehydrogenation
procedure.
The major
Eq 1
1668
No. 19
by-product verified
TABLE 1.
observed
by 'H and
is the bis-sulfenylated 13
C nmr spectroscopy
Dehydrogenative
Entry
Sulfenylation
phenol.
and, in some cases, comparison
4-t-butylcyclohexanone
2
cyclohexanone
group was
with data of known samples5.
% Yield
Product OH
1
of the phenylthio
of Cyclohexanonesa
Time (hr)
Ketone
The ortho position
OH
72
40
3
tetralone
4
3-isopropylcyclohexanone
18
5
2-methylcyclohexanone
25
6
&
192
120
(a) A typical procedure involved refluxing a mixture and 6 mmol of sodium methoxide in 15 ml of methanol. (e) Mp 73-77.5".
of 1 mmol of ketone, 4 mmol of diphenyl disulfide (c) See ref 5a. (d) See ref 5b. (b) Mp 73-4".
Only one alkyl group may be present at an alpha position. led to a 4:3 mixture
of mono- and bissulfenylated
ketones,
For example,
but no phenol.
2,6-dimethylcyclohexanone
A 2,2-dialkylcycohexanone
Eo 2
does not aromatize aromatization.
with dealkylation.
Diketone
5 undergoes
On the other hand, dehydrogenative
secosulfenylation
sulfenylation
unaccompanied
of cyclohexanones
by
is normally
much
No. 19
1669
h
(b) R = PhS
PhS faster than secosulfenylation Control
experiments
under these conditions intermediate
verify
in agreement
is noteworthy
long reaction since normally
A possible
with earlier
6
related
to the products
observations6.
ketones were isolated
times required monounsaturated
rationalization
C02CH3
(see Table 1, entry 6).
that the phenols
mono- and bissulfenylated
extraordinarily
analogs.
of cyclobutanones
(a) R = H
R
PhS
do not undergo
In the case of tetralone,
and shown to convert
in this case compared systems aromatize
sulfenylation
(eq 3) invokes a Favorskii-like
to product.
to the saturated
more rapidly
the The
cyclohexanones
than their saturated
reaction'
which requires
the
O0 SPh
7
_
8 Eq 3
O0
R&m_ qy (a) R = H
9
(b) R = PhS ability
to form the bissulfenylated
This rationale generation
enolate
nicelyaccommodatesall
of the equivalent
7 (or its enol) as a precursor
of our observations
of 7 (i.e. 10) requires II
especially
to the zwitterion
the tetralone
loss of aromaticity.
8.
case since the
Support for this inter-
so
c S
10 __ pretation
derives
11 __
from the conversion
which can be envisioned 2-enones
Q
by treating
to involve
of cyclopentanone
to 2-phenylthiocyclopent-2-enone
the enol forms related
a-dialkylsulfonium
ethylenedithiocyclohexanone
C02R
C02R
11 with base __
cyclohexanones 10
to _ 7 - I 9,the obtention
with sulfenimides',
of 2-arylthiocyclohex.
and the aromatization
--in the last case a Favorskii-like
of
process was also invoked
1670
No. 19
This reaction
provides
group for further
elaboration
the parent phenols
Acknowledgment. Health
access
to ortho substituted
provides
great opportunities.
and thus would constitute
Science
The flexibility
Desulfurization
one of the mildest
We wish to thank the National
for their generous
phenols.
methods
Foundation
of the phenylthio
also provides
entry to
for this transformation.
and the National
Institutes
of
support of our programs.
References 1.
B. M. Trost, T. N. Salzmann, and K. Hiroi, J. Amer. Chem. Sot., & 4487 (1976); D. Seebach and M. Teschner, Chem. Ber., 109, 1601 (1976). Also see T. Kumamoto, S. Kobayashi, and T. Mukaiyama, Bull. Chem. Sot. Japan, $5, 866 (1972). For a review see B. M. Trost, Accounts Chem. Res., submitted for publication,
2.
M. Oki, W. Funakoshi, Funakoshi, ibid., =, 44
3.
B. M. Trost and J. H. Rigby, J. Org. Chem., 41, 3217 (1976).
4.
M. S. Kablaoni, J. Org. Chem., a, 2126 (1974); H. Seeboth and B. Burnowski, @, 700, 50 (1966); D. A. Shirley and W. L. Dean, J. Amer. Chem. Sot., 77, 6077 (1955); W. von E. DoeriFand F. M. Beringer, ibid., 2, 2221 (1949); E. Beckman and H. Eickelberg, Chem. Ber., 2, 418 (1896).
5.
(a) G. E. Hilbert and T. B. Johnson, J. Amer. Chem. Sot., U. S. Pat. 3,188,352; Chem. Abstr., 63,
6.
T. Fujisawa, M. Yamamoto, and G. Tsuchihashi, 3. Org. Chem., 38, 687 (1973).
7.
F. G. Bordwell,
Accounts
8.
H. J. Monteiro,
J. Org. Chem., 42, 2324 (1977).
9.
T. Mukaiyama,
10.
s. Takano,
and A. Nakamura, 832 (1971).
T. Adachi,
S. Yamada,
Bull. Chem. Sot. Japan, 44, 828 (1971); M. Oki and W.
Synthesis,
2,
1526 (1929);
(b) W. Reifschneider,
624 (1972); T. Fujisawa
and T. Kojima,
Chem. Res., 3, 281 (1970).
and T. Kumamoto,
K. Tamigawa,
Bull. Chem. Sot. Japan, 44, 3155 (1971).
S. Hatakeyawa,
and K. Ogasawara,
Heterocycles,
4, 953 (1976).