Sulfoxide induced sigmatropic rearrangement (SISR) of methyl 1-methylsulfanylvinyl sulfoxides

Article abstract of DOI:10.1039/a701942d

Treatment of methyl 1-methylsulfanylvinyl sulfoxides with sodium thiophenolate in MeOH gives 1-methylsulfanylalk-1-en-3-ols.

Full text of DOI:10.1039/a701942d

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Sulfoxide induced sigmatropic rearrangement (SISR) of methyl
1-methylsulfanylvinyl sulfoxides
Bianca F. Bonini,a Mauro Comes Franchini,a Germana Mazzanti,*a Jan-Willem Slief,b Margreth A. Wegmanb
and Binne Zwanenburg*b
a Dipartimento di Chimica Organica ‘A. Mangini’, Universita` di Bologna, Viale Risorgimento 4, I-40136 Bologna, Italy
b Department of Organic Chemistry, NSR Centre for Molecular Structure, Design and Synthesis, University of Nijmegen,
Toernooiveld, 6525 ED Nijmegen, The Netherlands
Treatment of methyl 1-methylsulfanylvinyl sulfoxides with
sodium thiophenolate in MeOH gives 1-methylsulfanylalk-
1-en-3-ols.
treatment of 3a with a large excess of piperidine in MeCN at
room temperature did not give any reaction. Reaction at 85 °C
for five days, adding 10 equiv. of piperidine every day, gave a
70% yield of 1-methylsulfanylpent-1-en-3-ol 6a which had
almost exclusively the E configuration (E:Z ratio greater than
95:5). More convenient conditions involved treatment with 5
equiv. of sodium thiophenolate in MeOH at room temperature
for four days. In this manner 6a was obtained in 75% yield
almost exclusively in the E form. The formation of 6a from 3a
can readily be explained by invoking an initial base-induced
prototropic shift to give allylic sulfoxide 4a, which then
undergoes a 2,3-sigmatropic rearrangement to produce sulfen-
ate ester 5a. Subsequent thiophilic reaction of 5a with
thiophenolate then leads to product 6a. It is quite surprising that
thiophenoxide serves as thiophilic reagent1 as well as base.
These newly established conditions were also successful for the
sequential prototropic shifts and sigmatropic rearrangement
reactions of the substrates 3b–e. The corresponding 1-methyl-
sulfanylalk-1-en-3-ols 6b–e were all obtained in yields ranging
from 75–98%. The products 6a–e have been characterized by
IR, mass and NMR spectroscopic data.† The spectral character-
istics revealed that all products 6 predominantly have the E
configuration with E:Z ratio exceeding 90:10 (Scheme 2,
Table 2).
The sigmatropic rearrangement of allylic sulfoxides in the
presence of a thiophilic reagent leads to allylic alcohols.1 A
special sequence which includes this reaction is the rearrange-
ment of a-arylsulfinylacrylates to 4-hydroxyalk-2-enoate
esters.2 In this sequence a thiophilic base first gives an in situ
isomerization of the vinyl sulfoxide moiety into an allylic
sulfoxide, which then undergoes a 2,3-sigmatropic rearrange-
ment and a subsequent thiophilic cleavage of the thus-formed
intermediate sulfenic esters by the same base. A practical
variant of this synthesis of g-hydroxyalkenoic esters is the so-
called SPAC (sulfoxide piperidine and carbonyl) reaction3,4 in
which the sulfinylacrylates are prepared by a Knoevenagel-type
condensation of an appropriate aldehyde and arylsulfinyl
acetates, and subsequently rearranged under the same condi-
tions in a one-pot operation.
Here we report on a new related sulfoxide induced sigma-
tropic rearrangement (SISR) of methyl 1-methylsulfanylvinyl
sulfoxides. The required starting materials were conveniently
prepared from the corresponding dithiocarboxylic esters by
deprotonation with LDA and subsequent S-methylation. The
ketene dithioacetals thus prepared were oxidized to the
S-monoxides with 1 equiv. of MCPBA. In all cases the
E-isomers were formed preferentially. The dithioesters were
prepared from Grignard reagents and carbon disulfide, followed
by methylation with methyl iodide5 (Scheme 1). The products
1–3 were characterized by IR, mass and NMR spectroscopy.
The various compounds 3 prepared in this manner are listed in
the Table 1.
Table 1 Synthesis of compounds 3
Substituents
R
Product yields (%)a
RA
1
2
3
E:Z ratiob
a
b
c
d
e
Et
Pr
Bn
H
H
H
H
—
95
98
85
30
75
95
98
83
98
98
72
82
78
60
80
95:5
92:8
92:8
91:9
—
It is of interest to note that an alternative preparation of sulf-
oxides 3 from the S-oxides of dithioesters 1, by deprotonation
and subsequent S-alkylation of the intermediate vinylsulfenate
anion,6 was unsuccessful due to the limited stability7 of the
dithioesters of S-oxides and the formation of complex mixtures
of products.
PhO(CH2)2
–(CH2)3–
a Yields of pure isolated products. b Determined by NMR spectroscopy.
For the SISR reaction, first the recommended conditions for
the SPAC reactions were tried for substrate 3a. Prolonged
Me
O
Me
S
S
S
proton-shift
base
i, CS2
MgX
R
R
SMe
R
SMe
O
R
R
SMe
R
ii, MeI
R′
R′
3a–e
R′
4a–e
R′
1
i, LDA
ii, MeI
[2,3]
Me
OH
O SMe
S
SMe
thiophile
MCPBA
R
SMe
SMe
R
SMe
O
SMe
R′
6a–e
R′
5a–e
R′
R′
2
3
Scheme 1
Scheme 2
Chem. Commun., 1997
1011

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Table 2 Synthesis of 6 using thiophenoxide as thiophile
For E-6b: yellow oil; nmax(CCl4)/cm21 3620 (OH); 1H NMR (200 MHz,
CDCl3): d 0.88 (3 H, t, J 7.5 Hz), 1.20–1.75 (5 H, m), 2.20 (3 H, s), 4.10 (1
H, br q, J 6.5 Hz), 5.33 and 5.40 (1 H, dd, J 14.5 and 7.3 Hz), 6.25 (1 H, d,
J 14.5 Hz); 13C NMR (50.3 MHz, CDCl3): d 13.78, 14.31, 18.53, 39.38,
72.64, 126.25, 128.00; m/z 146 (M+), 129 (M+2H2O).
Substituents
Yield of 6
(%)a
R
RA
E:Z ratiob
For E-6c: yellow oil; nmax(CCl4)/cm21 3610 (OH); 1H NMR (200 MHz,
CDCl3): d 2.00 (1 H, br s), 2.26 (3 H, s), 2.80 and 2.90 (2 H, ABq, J 13.6,
7.8 and 5.8 Hz), 4.40 (1 H, br q, J 4.4 Hz), 5.45 and 5.52 (1 H, dd, J 15.6
and 7.0 Hz), 6.33 (1 H, d, J 15.6 Hz), 7.40–7.60 (5 H, m); 13C NMR (50.3
MHz, CDCl3): d 14.30, 44.02, 73.35, 126.32, 126.64, 128.25, 129.39,
137.40; m/z 194 (M+), 176 (M+2H2O).
a
b
c
d
e
Et
Pr
Bn
H
H
H
H
75
75
89
90
90
95:5
92:8
95:5
97:3
—
PhO(CH2)2
–(CH2)3–
For E-6d: yellow oil; nmax(CCl4)/cm21 3620 (OH); 1H NMR (200 MHz,
CDCl3): d 1.99 (2 H, q, J 6.0 Hz), 2.15 (1 H, br s), 2.22 (3 H, s), 3.95–4.20
(2 H, m), 4.35–4.50 (1 H, m), 5.42 and 5.47 (1 H, dd, J 15.7 and 6.7 Hz),
6.35 (1 H, d, J 15.7 Hz), 6.85–6.95 (3 H, m), 7.20–7.35 (2 H, m); 13C NMR
(50.3 MHz, CDCl3): d 13.98, 36.33, 64.24, 69.62, 114.12, 120.37, 126.37,
126.82, 129.05, 158.31; m/z 224 (M+).
a Yields of pure isolated products. b Determined by NMR spectroscopy.
1
For 6e: yellow oil; nmax(CCl4)/cm21 3615 (OH); H NMR (200 MHz,
It is worth noting that the yield is also high for the formation
of 6e, where the initial isomerization is accompanied by a
considerable increase of torsional strain.
CDCl3): d 1.30–1.50 (2 H, m), 1.50–1.70 (2 H, m), 1.85–1.95 (1 H, br s),
2.05 (3 H, s), 3.70–3.95 (2 H, m), 4.10–4.20 (1 H, m), 5.70–5.80 (1 H, m);
13C NMR (50.3 MHz, CDCl3): d 16.27, 21.25, 28.06, 35.14, 74.45, 119.78,
142.73; m/z 144 (M+).
The SISR reaction of sulfoxides 3, of which no precedent is
known in the literature, leads to g-hydroxyvinyl sulfides, which
can serve as a synthetic equivalent for b-hydroxy aldehydes8,9
The synthetic potential of this new SISR reaction is currently
under investigation, including chirality transfer from sulfur to
carbon when optically active sulfoxides are used as the
substrates. Furthermore, the SISR reaction will be investigated
for vinyl sulfoxides with other heteroatoms at the geminal
position of the sulfoxide group.
References
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2050.
Financial support of this work by the Ministero dell’
Universita` e della Ricerca Scientifica e Tecnologica (MURST),
Italy, is gratefully acknowledged. J. S. and M. A. W. are grateful
for the support from the Erasmus programme (ICP-95-NL-
1007/13).
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Footnote
† Selected data for E-6a: yellow oil; nmax(CCl4)/cm21 3620 (OH); 1H NMR
(200 MHz, CDCl3): d 0.90 (3 H, t, J 7.0 Hz), 1.50–1.65 (2 H, m), 1.70 (1
H, br s), 2.25 (3 H, s), 4.05 (1 H, q, J 7.0 Hz), 5.36 and 5.45 (1 H, dd, J 15.0
and 7.5 Hz), 6.30 (1 H, d, J 15.0 Hz); m/z 132 (M+), 114 (M+2H2O).
Received in Cambridge, UK, 19th March 1997; Com.
7/01942D
1012
Chem. Commun., 1997