Catalyst-Free and Solvent-Controlled Reductive Coupling of Activated Vinyl Triflates with Chlorotrimethylsilane by Magnesium Metal and Its Synthetic Application

Article abstract of DOI:10.1021/acs.orglett.8b00496

Vinylsilanes were directly prepared from the corresponding vinyl triflates under magnesium-promoted reductive conditions in THF with no transition metal catalyst, and gem-bis-silylated compounds were obtained in NMP. Investigation of the redox potential o

Full text of DOI:10.1021/acs.orglett.8b00496

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Catalyst-Free and Solvent-Controlled Reductive Coupling of
Activated Vinyl Triflates with Chlorotrimethylsilane by Magnesium
Metal and Its Synthetic Application
Hirofumi Maekawa,* Katsuaki Noda, Keisuke Kuramochi, and Tianyuan Zhang
Department of Materials Science and Technology, Nagaoka University of Technology, 1603-1, Kamitomioka-cho, Nagaoka, Niigata
940-2188, Japan
S
* Supporting Information
ABSTRACT: Vinylsilanes were directly prepared from the
corresponding vinyl triflates under magnesium-promoted
reductive conditions in THF with no transition metal catalyst,
and gem-bis-silylated compounds were obtained in NMP.
Investigation of the redox potential of starting materials and
products suggested that reductive coupling reactions of vinyl
triflates might be controlled by the reduction potential. A
variety of gem-bis-silylated compounds and 3-silyladipic acid
esters were easily synthesized in only two steps from vinyl triflates in high yields.
lkyl triflates are typical reagents for substitution reactions
Awith a good leaving group in synthetic organic chemistry,
whereas vinyl triflates can be usually used for substitution only in
the presence of a transition metal catalyst.1 Many examples of
transition-metal-catalyzed coupling reactions of vinyl triflates,1
aryl triflates,2 vinyl tosylates,3 aryl tosylates,4 and aryl mesylates5
can be found in organic synthesis; however, there are few
catalyst-free coupling reactions, which have been required for a
synthetic process. To our best knowledge, only substitution
reactions of vinyl triflates by nucleophilic attack of thiophenol6
and electrochemical carboxylation of vinyl triflates7 were
reported with no transition metal catalyst.
magnesium metal as a reductant.8 Ethyl cinnamates can be
acylated and silylated at the β-carbon atom of the carbonyl group
under reductive reaction conditions.9 In this study, we prepared
ethyl cinnamates with a triflate at the β-position of the carbonyl
group as starting vinyl triflates from easily available ethyl
benzoylacetates10 and investigated their coupling reactions. In
our previous results,8 aprotic polar solvents, such as DMF or
NMP, were required for magnesium-promoted reductive
coupling reactions of aromatic carbonyl compounds or aromatic
conjugated carbonyl compounds, whereas reductive coupling did
not occur in THF and acetonitrile.
Our first attempt to reduce 1a in NMP, DMF, and DMA
succeeded to give gem-bis-silylated compound 2a as a main
product with elimination of the triflate, and a reaction in
acetonitrile failed as we predicted (Table 1). Surprisingly,
Table 1. Solvent Effects of Magnesium-Promoted Reductive
a
Silylation of 1a
GC yield (%)
entry
solvent
2a
3a
4a
1
2
3
4
5
DMF
NMP
DMA
MeCN
THF
44
63
51
14
0
0
0
21
36
complex mixture
b
bc
,
0
3
61
a
b
c
Mg (6 equiv), TMSCl (8 equiv), rt, 8 h. Isolated yield. Z/E = 5/4.
We already reported reductive coupling reactions between
electron-deficient atoms and developed carbon−carbon bond or
carbon−silicon bond formation reactions by eco-friendly
Received: February 10, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b00496
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
reductive C−Si bond formation of 1a occurred, accompanied by
elimination of the triflate group in THF to afford Z/E isomers of
the corresponding vinylsilane selectively. As an example of
magnesium-promoted reaction in THF, reductive elimination of
a fluorine atom of the trifluoroacetyl group has been reported by
Uneyama and co-workers, and there is no direct formation of
carbon−carbon and carbon−silicon bonds at the sp2 carbon
atom.11 The leaving group is one of the most important factors in
this coupling reaction in THF, and only triflate gave the
substituted compound 4a; mesylate 5 was decomposed in situ,
and iodinated compound 6 was recovered quantitatively
(Scheme 1). Compounds 1a, 5, and 6 were converted into 2a
in good yields in NMP.
of 2a was obtained in NMP and DMF after complete
consumption of 8 (Scheme 2).12
Scheme 2. Reaction of Phenylacetylene Derivative under the
Same Reduction Conditions
From a total view of the results shown in Table 2 and Schemes
1 and 2, we measured the reduction potential of some starting
materials and products in NMP and THF; however, significant
peaks could not be detected in THF (Table 3). Reduction of 1a
Scheme 1. Effects of the Leaving Group in Reductive
Substitution of Ethyl Cinnamate Derivatives
Table 3. Hypothesis on the Reduction Potential Border of
Magnesium-Promoted Reduction in THF Estimated from the
a
Reduction Potential of Some Compounds in NMP
After the optimization of reaction conditions in THF and
NMP, the general tendency of the reactions was examined, and
the results are shown in Table 2. In NMP, about 20% of saturated
Table 2. Reductive Silylation of 1 by Magnesium Metal in
a
a
NMP and THF
Ar
isolated yield (%)
a
Cyclic voltammetry; Pt as working electrode, Pt as counter electrode,
entry
(1)
solvent
2
3
4
Ag/AgCl as reference electrode, NMP as solvent, nBu4NClO4 as
supporting electrolyte; scan rate = 0.2 V s−1, scan range = 0 to − 3.00
1
2
Ph
(1a)
NMP
THF
NMP
THF
NMP
THF
NMP
THF
NMP
THF
NMP
THF
57
50
58
42
49
47
2a
2b
2c
2d
2e
2f
20
17
21
22
27
25
3a
3b
3c
3d
3e
3f
c
c
V.
70
64
50
64
43
69
4a
3
4-ClC6H4
(1b)
was possible in THF and NMP, and all of the conjugated
carbonyl compounds, except 1a, could not be reduced in THF.
Product 4a was also inert in THF. Therefore, a hypothesis on the
magnesium-promoted reduction in THF is proposed from these
results; namely, there may be a reduction potential border for the
magnesium-promoted reduction in THF, and its value will be
around −1.40 V in NMP.13 In NMP and DMF, our previous
results suggested that the reduction potential limit of
magnesium-promoted reduction would be about −2.40 V.8
The approximately estimated value on the reduction potential
border enabled us to explore a simple way to prepare various
functionalized compounds.
4
4b
5
4-CH3C6H4
(1c)
d
6
4c
7
3-FC6H4
(1d)
c
8
4d
9
3-CH3OC6H4
(1e)
e
10
11
12
4e
2-naphthyl
(1f)
f
4f
a
b
Mg (6 equiv), TMSCl (6 equiv), rt, 5 h. Mg (3 equiv), TMSCl (3
c
d
e
f
equiv), rt, 5 h. Z/E = 10/9. Z/E = 1/1. Z/E = 10/7. Z/E = 5/4.
First, selective synthesis of 2 from 4 was investigated, and the
results are summarized in Table 4. Both Z and E isomers of 4a
were converted into the same gem-bis-silylated compound in
excellent yield with less monosilylated compound 3a (entries 1
and 2). The other gem-bis-silylated compounds were easily
synthesized from compounds 4 (entries 3−7).
Furthermore, application of a two-step strategy to 1 led to the
synthetic possibility of compounds attacked by two different
electrophiles at the electron-deficient β-carbon atom of the
monosilylation product 3 was detected as a byproduct, which
could be directly prepared from reductive silylation of ethyl
cinnamate 7 in previous results.9a,b In THF, vinylsilane 4 was
obtained as a sole product in good to moderate yield.
Reduction of phenylacetylene derivative 8 was carried out
because 1a was regarded as an equivalent of 8; however, it was
inert under the same reaction conditions in THF, and a low yield
B
DOI: 10.1021/acs.orglett.8b00496
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 4. Reductive Synthesis of gem-Bis-silylated Compounds
2 from Vinylsilanes 4 in NMP
Table 6. Reductive Carbon−Carbon Bond Formation of
a
a
Vinylsilane 4 in NMP
Ar
isolated yield (%)
entry
Ar (4)
isolated yield of 10 (%)
entry
4
2
3
1
2
3
4
5
6
4-ClC6H4 (4b-Z)
4-CH3C6H4 (4c-Z)
3-FC6H4 (4d-Z)
85
77
69
80
86
75
10b
10c
10d
10e
10f
1
2
3
4
5
6
7
Ph (4a-Z)
84
80
86
88
85
86
79
2a
2a
2b
2c
2d
2e
2f
12
17
10
8
3a
3a
3b
3c
3d
3e
3f
Ph (4a-E)
4-ClC6H4 (4b-Z)
4-CH3C6H4 (4c-Z)
3-FC6H4 (4d-Z)
3-CH3OC6H4 (4e-Z)
2-naphthyl (4f-Z)
3-CH3OC6H4 (4e-Z)
2-naphthyl (4f-Z)
4-FC6H4 (4g-Z)
11
9
10g
a
Mg (3 equiv), TMSCl (3 equiv), methyl acrylate (4 equiv), −10 °C,
10
a
4 h.
Mg (3 equiv), TMSCl (3 equiv), rt, 5 h.
will be reduced neither in THF nor in NMP, and that the
reductive coupling will start from the reduction of aromatic
conjugated ester 4.
Plausible reaction mechanisms for a series of coupling
reactions are shown in Scheme 4. The most important reaction
carbonyl group. Different silylating agents were applied to this
coupling reaction to give gem-bis-silylated compounds with
different silyl groups (9) in high yields, accompanied by a small
amount of 3a as a byproduct (Scheme 3).14
Scheme 3. Synthesis of gem-Bis-silylated Compounds with
Different Silyl Groups
Scheme 4. Plausible Reaction Mechanism for Reductive
Coupling of Ethyl Cinnamate Derivatives
Our next target to the coupling reaction of 4 was a new
carbon−carbon bond formation at the benzylic position, and
methyl acrylate was chosen as a reagent. As shown in Table 5,
Table 5. Solvent Effects of Magnesium-Promoted Reductive
and Unsymmetrical Carbon−Carbon Bond Formation
a
between 4a and Methyl Acrylate
entry
solvent
isolated yield (%)
1
2
3
DMF
NMP
THF
55
83
0
a
Mg (3 equiv), TMSCl (3 equiv), methyl acrylate (4 equiv), −10 °C,
4 h.
unsymmetrical coupling between two different α,β-unsaturated
esters in DMF and NMP occurred at β-positions smoothly to
give adipic acid ester (10a), and NMP was the best solvent.15
After optimization of the reaction conditions, scope and
limitation of this coupling reaction were investigated, as shown in
Table 6. Simple and direct coupling reaction between aliphatic
α,β-unsaturated ester and aromatic α,β-unsaturated ester 4
proceeded easily to give unsymmetrical adipic acid esters with
both an aromatic ring and a silyl group at the 3-position in high
yields. The reduction potential of methyl acrylate was measured
by cyclic voltammetry, and methyl acrylate showed no significant
reduction peak in NMP. This result indicates that methyl acrylate
is the reductive substitution reaction of 1a by magnesium metal
in the presence of chlorotrimethylsilane in THF and NMP
(mechanism A). Single electron transfer from magnesium metal
to vinyl triflate 1a in the presence of chlorotrimethylsilane in
THF or NMP, followed by elimination of the triflate as an anion
and the second electron transfer, will give a vinyl anion (12).16
Silylation of 12 afforded vinylsilane 4a as Z/E isomers, and no
further reaction occurred in THF. The second reductive
silylation of 4a proceeded in NMP to give gem-bis-silylated
compound 2a as a main product. Anion 12 will be stabilized by a
magnesium ion in THF, such as a vinyl Grignard reagent,
whereas 12 may be unstable in NMP and abstract a proton, for
C
DOI: 10.1021/acs.orglett.8b00496
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
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in part.17
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Agrawal, S.; De Angelis, F.; Nazeeruddin, M. K.; Krishna, N. V.;
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Isolation of 4a enabled us to explore novel synthetic processes
(mechanism B). In NMP, 4a could be reduced by magnesium
metal to give an anion radical species (13). An anionic species
derived from 13 or 13 itself will attack chlorotrialkylsilane,
nucleophilically, or will be subjected to Michael addition to
methyl acrylate, respectively.18 Protonation after the reaction
brought about selective formation of gem-bis-silylated com-
pounds 9 and adipic acid derivatives 10 in high yields.
In conclusion, magnesium-promoted reductive silylation of
aromatic vinyl triflates 1 proceeded with no transition metal
catalyst. The reaction could be controlled by the choice of
solvent, and this result suggested that the reduction by
magnesium in THF would have a potential limit much more
positive than that in NMP. Intermediates, vinylsilanes 4, which
would be generated in the reduction in NMP were trapped and
isolated selectively in the reduction in THF. These phenomena
were utilized in the selective introduction of two different
electrophiles to the electron-deficient carbon, especially syn-
thesis of gem-bis-silylated compounds 2, 9, and 3-silyladipic acid
esters 10. Related studies are in progress.
(7) Senboku, H.; Fujimura, Y.; Kamekawa, H.; Tokuda, M. Electrochim.
Acta 2000, 45, 2995.
(8) Recent results: (a) Zhang, T.; Maekawa, H. Org. Lett. 2017, 19,
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2017, 58, 206. (c) Zhang, T.; Zhang, Z.; Nishiyama, Y.; Maekawa, H.
Tetrahedron 2016, 72, 2293. (d) Maekawa, H.; Nishiyama, Y.
Tetrahedron 2015, 71, 6694. (e) Zhang, T.; Takano, A.; Nishiyama,
Y.; Maekawa, H. Tetrahedron 2015, 71, 2629. (f) Maekawa, H.; Takano,
A.; Watanabe, M. Tetrahedron Lett. 2014, 55, 6208. (g) Maekawa, H.;
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S.; Nishiguchi, I. Synlett 2012, 23, 401.
(9) Silylation: (a) Kundu, P. K.; Ghosh, S. K. Tetrahedron 2010, 66,
8562. (b) Ohno, T.; Nakahiro, H.; Sanemitsu, K.; Hirashima, T.;
Nishiguchi, I. Tetrahedron Lett. 1992, 33, 5515. (c) Picard, J.-P.;
Dunogues, J.; Calas, R. J. Organomet. Chem. 1974, 77, 167. (d) Picard, J.-
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M.; Ishino, Y.; Shibata, T.; Maekawa, H.; Nishiguchi, I. Org. Lett. 2001, 3,
3439. (f) Ohno, T.; Aramaki, H.; Nakahiro, H.; Nishiguchi, I.
Tetrahedron 1996, 52, 1943. (g) Lund, H.; Degrand, C. Tetrahedron
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.8b00496.
1H and 13C NMR spectra of 1b−f, 2a−f, 3d, 3e, (Z)-4b−g,
(E)-4b−f, 5, 9b−d, and 10a−g, and 19F NMR spectra of
2d, 3d, (Z)-4d, (E)-4d, (Z)-4g, 10d, and 10g (PDF)
AUTHOR INFORMATION
■
(10) Loreto, M. A.; Pompei, F.; Tardella, P. A.; Tofani, D. Tetrahedron
1997, 53, 15853.
Corresponding Author
*E-mail: maekawa@vos.nagaokaut.ac.jp.
ORCID
(11) (a) Amii, H.; Hatamoto, Y.; Seo, M.; Uneyama, K. J. Org. Chem.
2001, 66, 7216. (b) Mae, M.; Amii, H.; Uneyama, K. Tetrahedron Lett.
2000, 41, 7893. (c) Amii, H.; Kobayashi, T.; Hatamoto, Y.; Uneyama, K.
Chem. Commun. 1999, 1323. (d) Uneyama, K.; Mizutani, G.; Maeda, K.;
Kato, T. J. Org. Chem. 1999, 64, 6717.
Hirofumi Maekawa: 0000-0002-8192-8518
Notes
(12) The yield of 2a in DMF was 18%.
The authors declare no competing financial interest.
(13) It is impossible to have a precise discussion on the reduction
potential of the compounds treated in this reaction because our trial to
measure the reduction potential in THF failed, and the reduction
potentials of an organic compound in different solvents are not the same,
in general. The reduction potential in NMP has been used as a standard
to classify compounds.
ACKNOWLEDGMENTS
■
This work was supported in part by the Japan Society for the
Promotion of Science KAKENHI Grant Nos. 25410110 and
16K05768.
(14) Monosilylated compound 3a was obtained in 12−13% yield as a
byproduct in all cases.
REFERENCES
■
(15) Addition of chlorotrimethylsilane to this C−C bond formation
reaction is probably essential to activate the surface of magnesium metal
and to stabilize intermediates generated during the reaction. The typical
additives for Grignard reactions, such as iodine, iodomethane, and 1,2-
dibromoethane, were inappropriate for our magnesium-promoted
reduction.
(16) In the electron transfer reaction, formation of dianionic species is
thought to be unfavorable, and elimination of a triflate from 11 prior to
the second electron transfer is adopted in Scheme 4.7
(17) In NMP, monosilylated compound 3a may also be generated
from an anion radical species 13.
(18) Before hydrolysis, a ketene silyl acetal or a magnesium enolate
may be formed in situ.
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DOI: 10.1021/acs.orglett.8b00496
Org. Lett. XXXX, XXX, XXX−XXX