Mg-promoted stereoselective desulfonation of β-arylvinyl sulfone derivatives

Article abstract of DOI:10.1246/cl.2002.478

β-Arylvinyl ρ-tolylsulfones, easily prepared from base-catalyzed condensation of aromatic aldehydes with a variety of ρ-tolylsulfones, were efficiently transformed to the corresponding (E)-β-substituted aromatic olefins in a stereoselective manner through Mg-promoted reduction. The reaction may be initiated through electron transfer from Mg metal to the vinyl sulfones to give the corresponding anionic species followed by stereoselective elimination of a sulfonyl group.

Full text of DOI:10.1246/cl.2002.478

478
Chemistry Letters 2002
Mg-Promoted Stereoselective Desulfonation of ꢀ-Arylvinyl Sulfone Derivatives
Ikuzo Nishiguchi,ꢀ Takeshi Matsumoto, Takeshi Kuwahara, Makoto Kyoda, and Hirofumi Maekawa
Department of Chemistry, Nagaoka University of Technology, 1603-1 Kamitomioka-cho, Nagaoka, Niigata 940-2188
(Received January 25, 2002; CL-020090)
Table 1. Mg-Promoted desulfonation of ꢀ-aryl-ꢁ-(methylthio)vinyl
tolylsulfones
ꢀ-Arylvinyl p-tolylsulfones, easily prepared from base-cata-
lyzed condensation of aromatic aldehydes with a variety of p-
tolylsulfones, were efficiently transformed to the corresponding
(E)-ꢀ-substituted aromatic olefins in a stereoselective manner
through Mg-promoted reduction. The reaction may be initiated
through electron transfer from Mg metal to the vinyl sulfones to give
the corresponding anionic species followed by stereoselective
elimination of a sulfonyl group.
X
Yield 3/%
Epa/V (2)
H (2a)
p-F (2b)
68 (3a)
72 (3b)
À1.63
À1.62
À1.68
—
p-MeO (2c)
p-Cl (2d)
m-Cl (2e)
o-Cl (2f)
p-Me (2g)
5
3c)
7 (
71 (3d)
73 (3e)
63 (3f)
67 (3g)
—
—
À1.63
aReduction potential (V vs Ag/AgCl), Conditions; Solvent DMSO,
Supporting Electrolyte n-Bu4NClO4, Electrodes Pt, Sweep Rate 200 mV/s.
Stereoselective synthesis of olefins are one of the most
important and challenging subjects in organic synthesis.1{3 In this
study, we wish to report a novel stereoselective method for
formation of (E)-ꢀ-substituted aromatic olefins (3, 6) through Mg-
promoted desulfonation of ꢀ-arylvinyl p-tolylsulfones (2, 4, 5),
easily prepared from base-catalyzed condensation of aromatic
aldehydes with a variety of p-tolylsulfones.
anion radical, is so easy to lose p-toluenesulfinate anion that only a
little of its reverse oxidation peak was observed, as shown in Figure
1. It was also clarified that the product (3a) could be hardly reduced
in this reaction since reduction potential of 3a was much more
negative (À2:5 V vs Ag/AgCl). These electrochemical results as
well as our recent study13{15 on Mg-promoted reductive cross-
coupling reactions of aryl-substituted active olefins may suggest
that the present desulfonation proceeded through electron transfer
reaction promoted by Mg metal.
As one of the typical starting sulfones, ꢀ-aryl-ꢁ-(methylthio)-
vinyl p-tolylsulfones (2) were prepared from various aromatic
aldehydes and (methylthio)methyl p-tolylsulfone (MT-sulfone)4
(1) in 85–96% yields according to the modified method reported by
Ogura and coworkers.5 These sulfones exclusively consisted of one
stereoisomers(>99%) and characterized them as the (E)-isomers
based on NMR analysis.6;7 UV-irradiation of (E)-ꢀ-phenyl-ꢁ-
(methylthio)vinyl p-tolylsulfone (2a) led to photochemical iso-
merzation8 to form the stereoisomeric mixture (ðEÞ=ðZÞ ¼ 95=5),
which was treated by column chromatography to give the new
stereoisomeric mixture (ðEÞ=ðZÞ ¼ 7=3). Treatment of either of 2a
((E)-isomer) or the 7/3 mixture with Mg turnings9 (3 equiv) in
dimethyl sulfoxide (DMSO)10 containing trimethylsilyl chloride (5
equiv: TMSCl)11 at room temperature for 1 day brought about
stereoselective desulfonation to give (E)-ꢀ-(methylthio)styrene
(3a) as a sole product in 68 and 69% yields, respectively. Under the
same reaction conditions, Mg-promoted reduction of a variety of ꢀ-
aryl-ꢁ-(methylthio)vinyl p-tolylsulfones (2a-g) afforded the corre-
sponding (E)-ꢁ-aryl-ꢀ-(methylthio)ethylenes (3a-g) in 57–73%
yields in a stereoselective manner, as shown in Scheme 1 and
Table 1.
Figure 1. Cyclic voltammetry of 2a. Working electrode(Pt), Counter
electrode(Pt), Reference electrode(Ag/AgCl), in DMSO/n-Bu4NClO4,
Sweep rate: 200 mV/s.
Furthermore, the present stereoselective desulfonation was
found to proceed smoothly for other aromatic vinyl sulfones (4a-d),
and (E)- and (Z)-ꢁ-(methylthio)styryl methyl sulfoxides (5a,b). For
example, similar Mg-promoted reduction in DMF of stereoisomeric
mixtures of ꢀ-phenyl-ꢁ-alkylvinyl p-tolylsulfones (4a-d),16;17
readily prepared from base-catalyzed condensation of benzalde-
hyde and alkyl p-tolylsulfones in 77–88% yields, led to efficient and
stereoselective desulfonation to afford the corresponding (E)-ꢀ-
alkylstyrenes (6a-d) exclusively in 72–85% yields, as shown in
Scheme 2 and Table 2.
Scheme 1.
Cyclic voltammetry of 2a, 2b, 2c, and 2g showed that they were
readily accessible to electron transfer type of reduction at À1:62–
À1:68 V vs Ag/AgCl,12 and the substrates possessing more positive
reduction potential were transformed to the corresponding products
more efficiently than those with more negative potential although
the differences among the yield of the products (3a, 3b, 3c, 3g) were
relatively small (Table 1). Also cyclic voltammetry of 2a indicated
that the anion species generated by electron transfer, possibly the
(E)- and (Z)-ꢁ-(methylthio)styryl methyl sulfoxides (5a,b)8;18
were also reduced by Mg turnings in DMF or DMSO containing
TMSCl and a small amount of phenol as a proton donor to give (E)-
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
479
compounds, satisfactory yield, non-polluted feature of Mg metal,
and may therefore provide one of specific methods for stereo-
selective synthesis of (E)-ꢀ-substituted aryl olefins.
Scheme 2.
This study was supported by a Grant-in–Aid for Scientific
Research on Priority Areas (No. 13029038) from Ministry of
Education, Science, Sports and Culture, Japan.
Table 2. Synthesis and Mg-promoted stereoselective desulfonation of ꢀ-
phenyl-ꢁ-alkylvinyl tolylsulfones 4
4a-d
Yield/%
6a-d
R
E/Z
E/Z
Yield/%
References and Notes
1
‘‘Comprehensive Organic Synthesis,’’ ed. by B. M. Trost and I. Fleming,
Pergamon, Oxford (1991), Vol. 6, pp 949–1070.
CH3
CH2CH3
55/45
68/32
69/31
90/10
77
88
88
87
>99 (E)
>99 (E)
98/2
72
81
75
85
2
3
4
A. D. Buss and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1985, 2307.
K. Ando, J. Org. Chem., 64, 6815(1999).
K. Ogura, N. Yahata, J. Watanabe, K. Takahashi, and H. Iida, Bull. Chem.
Soc. Jpn., 56, 3543 (1983).
5K. Ogura, J. Watanabe, K. Takahashi, and H. Iida, J. Org. Chem., 47, 5404
CH2CH2CH3
CH2C6H5
99/1
ꢀ-(methylthio)styrene (3a) in a stereoselective manner accompa-
nying the formation of a small amount of ꢀ, ꢀ-bis(methylthio)styr-
ene (7), as shown in Scheme 3.19;20
(1982).
6
Chemical shift (ꢂ value) of an olefinic proton of 2a was observed at
8.26 ppm (in CDCl3) while calculated ones6 for its (E) and (Z)-isomers
were 7.66 and 7.27 ppm, respectively. Since some deshielding (0.6 ppm)
can be elucidated by hydrogen bonding of the olefinic proton with an
oxygen atom of the sulfonyl group, 2a was identified as the (E)-isomer.
An olefinic proton of the other isomer came out at ꢂ ¼ 7:18 ppm.
R. M. Silverstein, G. C. Bassler, and T. C. Morrill, ‘‘Spectrometric
Identification of Organic Compounds,’’ 5th ed., John Wiley & Sons, Inc.,
New York (1991) p 215.
7
8
9
K. Ogura and G. Tsutihashi, Tetrahedron Lett., 15, 1383 (1972).
Mg turnings for Grignard reaction was used without any pre-treatment.
10 The reaction of 2a in DMSO was found to give the optimum yield (68%)
among those in other aprotic polar solvents such as DMF (45%), sulforane
(40%), DMAC (23%), THF (20%), and acetonitrile (14%).
11 Although the detailed role of TMSCl is still unclear, two main roles may
be postulated, i.e., activation of the surface of Mg metal and stabilization
of anionic intermediates generated by electron transfer from Mg metal.
12 Mg metal is thought to be able to reduce readily compounds possessing
less negative reduction potential than À1:80 V vs Ag/AgCl under these
conditions. See Ref. 11.
13 M. Kyoda, T. Yokoyama, T. Kuwahara, H. Maekawa, and I. Nishiguchi,
Chem. Lett., 2002, 228.
14 T. Ohno, Y. Ishino, Y. Tsumagari, and I. Nishiguchi, J. Org. Chem., 60,
458 (1995).
Scheme 3.
Although a detailed reaction mechanism for the present
stereoselective desulfonation is ambiguous as yet, the following
scheme may be proposed as one of the most plausible mechanisms,
as shown in Scheme 4. The first electron transfer from Mg metal to
the starting substrate 2, 4 or 5 generates the corresponding anion
radical (8), whose carbanion center and an oxygen atom of the
sulfonyl or sulfinyl group may be coordinated by Mg2þ cation,
causing one conformation (9A) more favorable than the other (9B).
Subsequent stereoselective elimination of the sulfonyl or sulfinyl
group from the favorable conformation (9A) followed by the second
electron transfer from Mg metal may give a (E)-vinyl anion (10),
which is protonated by a proton donor such as solvent,21 phenol or
moisture in solvent.
15T. Ohno, M. Sakai, Y. Ishino, T. Shibata, H. Maekawa, and I. Nishiguchi,
Org. Lett., 3, 3439 (2001).
16 J. Wildeman and A. M. van Leusen, Synthesis, 1979, 733.
17 G. E. Vennstra and Zwanenburg, Synthesis, 1975, 519.
18 A. Kunugi and K. Abe, Chem. Lett., 1984, 159.
19 Ogura et al20 reported the interesting result that treatment of 5a with
C2H5MgBr led to stereospecific reductive desulfination to give (Z)-ꢀ-
(methylthio)styrene in a 79% yield.
20 K. Ogura, K. Arai, and G. Tsuchihashi, Bull. Chem. Soc. Jpn., 55, 3669
(1982).
As a conclusion, Mg-promoted reduction of ꢀ-arylvinyl p-
tolylsulfones, easily prepared from aromatic aldehydes with various
p-tolylsulfones, brought about efficient and stereoselective forma-
tion of the corresponding (E)-ꢀ-substituted aromatic olefins. The
reaction may be characterized by simple procedure, mild condi-
tions, high stereoselectivity, easy availability of the starting
21 Use of DMSO-d6 as a solvent and addition of 5equiv of D 2O in the solvent
of DMSO in the reaction of 2a led to the formation of a mixture of 3a-D
and 3a-H in the ratios of 1 : 1 and 9 : 1, respectively while addition of
5equiv of D 2O after the reaction in DMSO resulted in no formation of 3a-
D to give 3a-H as the sole product.
Scheme 4.