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Regioselectivity of metalation of alkylmercaptoolefins
0040-4039/79/1029-4277$02/00/O
Tetrahedron Letters No. 44, pp 4277 - 4280. @Pergamon Press Ltd. 1979. Printed in Great Britain.
REGIOSELECTIVITY
Richard
OF METALATION
Chemie,
Postfach
Abstract:
')
+, Heike Speer, and Bruno Schmid
R. Schmidt
Fachbereich
OF ALKYLMERCAPTOOLEFINS
UniversitBt
5560, D-7750
Konstanz
Konstanz
The monosulfoxide of cis-dialkylmercaptoethylene 5 and the B-aZkyZmercapto acrylnitri-
le =15 deZiver on deprotonation with tert.-butyllithiwnalmost exclusively a-deprotonuted species. According to reactions with electrophiles these functionally substituted vinyllithiwn derivatives are configurationakly labile.
Cis-1.2-dialkylmercaptoethylenes philes delivering
(L) are easily deprotonated
2 2). Hydrolysis
compounds
thon for 4 or 2 3). Alkylmercapto
ductive
effect of the alkoxy
is also effective Monooxidation 7 = according quenching
group
with methanol-O-d
steric,
labile,
leading
intramolecular supported
complexation
results
via 2. In addition, experiments
effects,
which
12 does not isomerize
positions
(table of
small amounts
of A&J __- via ip are that 2 is configura-
demonstrate lability
clearly
in THF and
group a-deprotonation
is supported
by electronic,
give B a lower energy.
under these reaction
conditions,
may favour
the formation
of LA. The deuteration
of lithiated
6 with methyl
iodide and dimethyl
As expect-
even though
experiments
are
disulfide
as electro-
A@ ___ and 136, _-_ iis, respectively. All experiments demonstrate g-i9 react with electrophiles with retention of configuration.
that vinyl-
to Qb, _--
lithium derivatives Similar
complexation
at the vinylic
effect of the sulfoxide
dependent
to the cyclic compound
of 8 with tert.-butyllithium
to &?a ___ via 8. This configurational
derivative
by the reaction
leading
to &
effect
to the alkoxy group
7) .
mono-deprotonation
inductive
leading
complexation
2, which does not rearrange
deprotonation
Temperature
and intramolecular
ed, vinyllithium
philes
of deprotonation
shows complete
with the stronger
formed by B-deprotonation.
for by the anion stabilizing
6) . Possibly, intramolecular
investigations;
$ takes place preferentially
tionally
of 2 are aimed to show if 4 is a syn-
group is at least compensated
in ag
of 2 leads to cis-monosulfoxide
1). In accordance
electro-
enolethers
in the regioselectivity
to 1H-NMR
positions;
and dienolethers react with strong bases to the 435) 22, zh, respectively . Acidification by the strong negative in-
vinyllithium-derivatives
of the alkylmercapto
experiments
at the vinylic
are obtained
Only little !3-deprotonation
with R-ethylmercapto is observed
acrylonitrile
with tert.-butyllithium
4277
ii (cis:trans
= 1:3); table 2.
in THF; quenching
with methanol-
4278
No. 44
CN
I
RS
%
I
R=
g
Et
/a 1. Base 2. Ee
7
4
H \/CN
HO..
SR
=a:
E =
D
$:
E =
CH3
=c:
E =
C2H5S
i: E =
eN
II
NC
Lie i RSii,
C2H5-;IH
==
’
,,I:’
g
22
OH Table 2:
Deprotonation
Compound
E-X
of 12 and Reaction Temperature COCI
with Electrophiles Yield [%I
a) Reaction $j
product
[partsIb)
42
g
P
D-OCH3
-113
95
60
32
8
b =
CH3-J
-113
80
80
15
5
- 80
60
75
20
5
- 20
30
75
20
5
C =
C2H5S-SC2H5
-113
51
16 c,
82 c) <
1
C2H5-CH=O
-113
52
82
16
a) Solvent:
THF; base 1.2 equivalents
b) lH-NMR-determination. Table
3:
'H-NMR-Data
b =
HB: 6.98
assignments
of the electrophile
after 60 min.
a)
a =
a) 80 MHz, CDC13,
addition
c) see table 3.
Compound
b) These
t-BuLi;
2
<2
E
!I
(t)
HB: 6.80 (t)
HB: 6.37
Hc1: 6.02
(s)
HB: 7.28 (s)
(t)
H : 5.99 (s)
Ha: 6.37 (s)
Ha: 7.10 (t)
H;: 6.71 (q)
Ha: 7.10 (s) b)
HB: 7.17 (s)
HB: 7.27 (t)
HB: 7.21 (q)
HB: 7.21 (s) b,
HB: 7.27 (s)
Hc,: 5.07 (t)
Ha: 4.87 (q)
s-values, can
be
Tetramethylsilan interchanged.
internal.
No. 44
4279 RS
x
H
I
RS RS
x
1 =
H
H
I
RS
E
2 =
9’. R--S
Table
1:
RS
H
Deprotonation
Compound
E-X
D-OCH3
x =9
R! RS
H
Temperature
11 =
g
of i and Reaction
PC1 a =
A
I
& =8
‘fLi
with Electrophiles
Yield
r.%I
a)
Reai;ion
pr;;uct
[P$I
=_
-120
100
95
5
-100
100
31
59
10
- 80
100
73
17
10
b =
CH3-J
-120
89
95
5
‘;
CH3S-SCH3
-120
100
85
15
a) Solvent:
THF, base: 1.1 equiv.
b) NMR-determination. c) Compounds
14 were not isolated. _=
t-BuLi;
addition
of the electrophile
after 10 min.
b,
No. 44
O-d leads to little 18s; ___ cis-compound !s was not found at all. Even though the anion stabilizing effect of an a-alkylmercapto group is very important in "Umpolung" reactions 8) , it is outweighed
by the electronic
tion. However,
effect of the cyano group: deprotonation
the intermediate
brium with the cis-compound @.
An influence
trophile; sulfide
Xb, ___
EE or the cumulene
of temperature
and propionaldehyde
calculations
if electronic
effects,
the B hydrogen
&,
'H-NMR-Data
was not observed
17g were received; ___ in table 3.
with trans+aminoacrylonitrile
atom depends
greatly
complexation
18~ and ___ &lg were present only ---
and solvation
are included
7) . Acidity
effect, which
a-deprotonation
with the experimental
the kinetically
of
is lower for the alkylmer-
and thermodynamically
findings,
if compared
preferred
with the !3-
system 7yg).
References
and Footnotes
Part 8. This work was supported
Fonds der Chemischen 2) 8. Schmid,
di-
a-deprotonation,
therefore,
1) Vinyl Anions,
iodide as elec-
with diethyl
preferential
on the inductive
of iz is in agreement
at the a-posi-
support
capto group than for the amino group;
aminoacrylonitrile
with methyl
Accordingly,
17'~ and Ni, ___
intramolecular
occurs
20 -_ is even at -113'C in equilianion Ei, leading not only to &i'n but also to
in the same proportion.
are compiled
mainly
derivative
on this behaviour
lib --- and I& -__ were formed
in trace amounts. Theoretical
trans-vinyllithium
Industrie.
Diplomarbeit
by the Deutsche
Forschungsgemeinschaft
and the
- Part 7: see ref. 7.
Univ. Stuttgart
1976; R.R. Schmidt
and B. Schmid,
Tetrahedron
lett.
1977, 3583 3) B. Schmid,
Thesis,
in preparation.
4) I. Vlattas,
L.D. Vecchia,
5) W. Kreiser,
Second
6) This effect
is shown, for instance,
tion: D.W. Sloccum 7) R.R. Schmidt, 8) D. Seebach, 9) R.R. Schmidt
A.O. Lee, J.Am.Chem.Soc.
IUPAC Symposium
and L. Gieser,
J. Talbiersky
Angew.Chem.
2008 (1976)
Synthesis,
in the convenient
J.Org.Chem.
and P. Russegger,
Israel, September
deprotonation
and J. Talbiersky,
Angew.Chem.
in Germany 6 August
1979)
1978.
of thiophenes
41, 3668 (1976) and references Tetrahedron
Lett. submitted
-91, 259 (1979); Angew.Chem.Int.Ed.Engl.
(1977). (Received
on Organic
98,
at 2 posi-
cited therein.
for publication.
-18, 239 (1979).
-89, 891 (1977); Angew.Chem.Int.Ed.Engl.
-16, 853
Tetrahedron Letters No. 44, pp 4277 - 4280. @Pergamon Press Ltd. 1979. Printed in Great Britain.
REGIOSELECTIVITY
Richard
OF METALATION
Chemie,
Postfach
Abstract:
')
+, Heike Speer, and Bruno Schmid
R. Schmidt
Fachbereich
OF ALKYLMERCAPTOOLEFINS
UniversitBt
5560, D-7750
Konstanz
Konstanz
The monosulfoxide of cis-dialkylmercaptoethylene 5 and the B-aZkyZmercapto acrylnitri-
le =15 deZiver on deprotonation with tert.-butyllithiwnalmost exclusively a-deprotonuted species. According to reactions with electrophiles these functionally substituted vinyllithiwn derivatives are configurationakly labile.
Cis-1.2-dialkylmercaptoethylenes philes delivering
(L) are easily deprotonated
2 2). Hydrolysis
compounds
thon for 4 or 2 3). Alkylmercapto
ductive
effect of the alkoxy
is also effective Monooxidation 7 = according quenching
group
with methanol-O-d
steric,
labile,
leading
intramolecular supported
complexation
results
via 2. In addition, experiments
effects,
which
12 does not isomerize
positions
(table of
small amounts
of A&J __- via ip are that 2 is configura-
demonstrate lability
clearly
in THF and
group a-deprotonation
is supported
by electronic,
give B a lower energy.
under these reaction
conditions,
may favour
the formation
of LA. The deuteration
of lithiated
6 with methyl
iodide and dimethyl
As expect-
even though
experiments
are
disulfide
as electro-
A@ ___ and 136, _-_ iis, respectively. All experiments demonstrate g-i9 react with electrophiles with retention of configuration.
that vinyl-
to Qb, _--
lithium derivatives Similar
complexation
at the vinylic
effect of the sulfoxide
dependent
to the cyclic compound
of 8 with tert.-butyllithium
to &?a ___ via 8. This configurational
derivative
by the reaction
leading
to &
effect
to the alkoxy group
7) .
mono-deprotonation
inductive
leading
complexation
2, which does not rearrange
deprotonation
Temperature
and intramolecular
ed, vinyllithium
philes
of deprotonation
shows complete
with the stronger
formed by B-deprotonation.
for by the anion stabilizing
6) . Possibly, intramolecular
investigations;
$ takes place preferentially
tionally
of 2 are aimed to show if 4 is a syn-
group is at least compensated
in ag
of 2 leads to cis-monosulfoxide
1). In accordance
electro-
enolethers
in the regioselectivity
to 1H-NMR
positions;
and dienolethers react with strong bases to the 435) 22, zh, respectively . Acidification by the strong negative in-
vinyllithium-derivatives
of the alkylmercapto
experiments
at the vinylic
are obtained
Only little !3-deprotonation
with R-ethylmercapto is observed
acrylonitrile
with tert.-butyllithium
4277
ii (cis:trans
= 1:3); table 2.
in THF; quenching
with methanol-
4278
No. 44
CN
I
RS
%
I
R=
g
Et
/a 1. Base 2. Ee
7
4
H \/CN
HO..
SR
=a:
E =
D
$:
E =
CH3
=c:
E =
C2H5S
i: E =
eN
II
NC
Lie i RSii,
C2H5-;IH
==
’
,,I:’
g
22
OH Table 2:
Deprotonation
Compound
E-X
of 12 and Reaction Temperature COCI
with Electrophiles Yield [%I
a) Reaction $j
product
[partsIb)
42
g
P
D-OCH3
-113
95
60
32
8
b =
CH3-J
-113
80
80
15
5
- 80
60
75
20
5
- 20
30
75
20
5
C =
C2H5S-SC2H5
-113
51
16 c,
82 c) <
1
C2H5-CH=O
-113
52
82
16
a) Solvent:
THF; base 1.2 equivalents
b) lH-NMR-determination. Table
3:
'H-NMR-Data
b =
HB: 6.98
assignments
of the electrophile
after 60 min.
a)
a =
a) 80 MHz, CDC13,
addition
c) see table 3.
Compound
b) These
t-BuLi;
2
<2
E
!I
(t)
HB: 6.80 (t)
HB: 6.37
Hc1: 6.02
(s)
HB: 7.28 (s)
(t)
H : 5.99 (s)
Ha: 6.37 (s)
Ha: 7.10 (t)
H;: 6.71 (q)
Ha: 7.10 (s) b)
HB: 7.17 (s)
HB: 7.27 (t)
HB: 7.21 (q)
HB: 7.21 (s) b,
HB: 7.27 (s)
Hc,: 5.07 (t)
Ha: 4.87 (q)
s-values, can
be
Tetramethylsilan interchanged.
internal.
No. 44
4279 RS
x
H
I
RS RS
x
1 =
H
H
I
RS
E
2 =
9’. R--S
Table
1:
RS
H
Deprotonation
Compound
E-X
D-OCH3
x =9
R! RS
H
Temperature
11 =
g
of i and Reaction
PC1 a =
A
I
& =8
‘fLi
with Electrophiles
Yield
r.%I
a)
Reai;ion
pr;;uct
[P$I
=_
-120
100
95
5
-100
100
31
59
10
- 80
100
73
17
10
b =
CH3-J
-120
89
95
5
‘;
CH3S-SCH3
-120
100
85
15
a) Solvent:
THF, base: 1.1 equiv.
b) NMR-determination. c) Compounds
14 were not isolated. _=
t-BuLi;
addition
of the electrophile
after 10 min.
b,
No. 44
O-d leads to little 18s; ___ cis-compound !s was not found at all. Even though the anion stabilizing effect of an a-alkylmercapto group is very important in "Umpolung" reactions 8) , it is outweighed
by the electronic
tion. However,
effect of the cyano group: deprotonation
the intermediate
brium with the cis-compound @.
An influence
trophile; sulfide
Xb, ___
EE or the cumulene
of temperature
and propionaldehyde
calculations
if electronic
effects,
the B hydrogen
&,
'H-NMR-Data
was not observed
17g were received; ___ in table 3.
with trans+aminoacrylonitrile
atom depends
greatly
complexation
18~ and ___ &lg were present only ---
and solvation
are included
7) . Acidity
effect, which
a-deprotonation
with the experimental
the kinetically
of
is lower for the alkylmer-
and thermodynamically
findings,
if compared
preferred
with the !3-
system 7yg).
References
and Footnotes
Part 8. This work was supported
Fonds der Chemischen 2) 8. Schmid,
di-
a-deprotonation,
therefore,
1) Vinyl Anions,
iodide as elec-
with diethyl
preferential
on the inductive
of iz is in agreement
at the a-posi-
support
capto group than for the amino group;
aminoacrylonitrile
with methyl
Accordingly,
17'~ and Ni, ___
intramolecular
occurs
20 -_ is even at -113'C in equilianion Ei, leading not only to &i'n but also to
in the same proportion.
are compiled
mainly
derivative
on this behaviour
lib --- and I& -__ were formed
in trace amounts. Theoretical
trans-vinyllithium
Industrie.
Diplomarbeit
by the Deutsche
Forschungsgemeinschaft
and the
- Part 7: see ref. 7.
Univ. Stuttgart
1976; R.R. Schmidt
and B. Schmid,
Tetrahedron
lett.
1977, 3583 3) B. Schmid,
Thesis,
in preparation.
4) I. Vlattas,
L.D. Vecchia,
5) W. Kreiser,
Second
6) This effect
is shown, for instance,
tion: D.W. Sloccum 7) R.R. Schmidt, 8) D. Seebach, 9) R.R. Schmidt
A.O. Lee, J.Am.Chem.Soc.
IUPAC Symposium
and L. Gieser,
J. Talbiersky
Angew.Chem.
2008 (1976)
Synthesis,
in the convenient
J.Org.Chem.
and P. Russegger,
Israel, September
deprotonation
and J. Talbiersky,
Angew.Chem.
in Germany 6 August
1979)
1978.
of thiophenes
41, 3668 (1976) and references Tetrahedron
Lett. submitted
-91, 259 (1979); Angew.Chem.Int.Ed.Engl.
(1977). (Received
on Organic
98,
at 2 posi-
cited therein.
for publication.
-18, 239 (1979).
-89, 891 (1977); Angew.Chem.Int.Ed.Engl.
-16, 853