A novel reaction of dimethylsulfonium methylide with Michael acceptors: Application to the synthesis of difficulty accessible vinyl silanes and styrenes

Article abstract of DOI:10.1039/b211279e

Rather than the usual cyclopropanation and Peterson-type olefination, conditions for a novel elimination reaction from the adduct of dimethylsulfonium methylide and 2-silylalk-ylidene/arylidene malonate/cyanoacetate/phosphonoacetate leading to geminally s

Full text of DOI:10.1039/b211279e

A novel reaction of dimethylsulfonium methylide with Michael acceptors:
application to the synthesis of difficultly accessible vinyl silanes and
styrenes†
Sunil K. Ghosh,* Rekha Singh and Sonali M. Date
Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India.
E-mail: ghsunil@magnum.barc.ernet.in
Received (in Cambridge, UK) 20th November 2002, Accepted 24th January 2003
First published as an Advance Article on the web 7th February 2003
Table 1 Effect of solvent and base on cyclopropanation
Rather than the usual cyclopropanation and Peterson-type
olefination, conditions for a novel elimination reaction from
the adduct of dimethylsulfonium methylide and 2-silylalk-
ylidene/arylidene malonate/cyanoacetate/phosphonoacetate
leading to geminally substituted vinyl silanes or styrenes,
respectively, have been established.
Entry
DMSO/THF
Equiv. base 4a/5aa
% Yieldb
Dimethylsulfonium methylide (1), generated from a trime-
thylsulfonium salt and a base is known to react with an aldehyde
or a ketone to give an epoxide by an overall methylene
insertion.1 Excess reagent could lead to the formation of allylic
alcohol by further addition of the ylide on the epoxide.2 In line
with the carbonyl compounds, imines give aziridines with 1.1
The ylide can be used for the conversion of halides and
mesylates to one-carbon homologated terminal alkenes.3 It can
also add to Michael acceptors in 1,4-fashion to provide
cyclopropanes.1 Thus, the reaction of the ylide 1 with the
Michael acceptor 2 gives a betaine intermediate 3 which in
principle can undergo various reactions (Scheme 1), the driving
force in all cases being the elimination of Me2S. The most well
known amongst these is the formation of cyclopropane 4 (path
‘a’ Scheme 1). The other possible modes of reaction of
intermediate 3 are elimination with a loss of proton resulting in
formation of an olefin 5 (path ‘b’), and a Peterson-type
olefination (R = silyl group) with loss of the silyl group leading
to olefin 6 (path ‘c’). The formation of cyclopropane 4 has been
well studied while that of olefin 5 or 6 has not been observed.
We found that under specific reaction conditions and depending
upon the substituents (R, E1 and E2) on 2, the formation of 5
could be made exclusive.
Recently, we have developed a method for the preparation of
the 2-silyl alkylidene malonate 2a and used as a Michael
acceptor in the preparation of a functionalised b-silyl ketone.4
When 2a was reacted with 1, generated from trimethylsulfon-
ium iodide1 and sodium dimsylate (1 equiv.) in DMSO–THF
(70+30) at 0 °C, we obtained the anticipated product, cyclopro-
pane 4a (Table 1; entry 1). Surprisingly, when the amount of
base was increased (1.5 equiv.), the formation of vinyl silane 5a
could be found in addition to cyclopropane 4a (entry 2). The
formation of 5a was highly solvent dependent as shown in Table
1
2
3
4
5
6
7
8
70+30
70+30
70+30
60+40
40+60
30+70
30+70
30+70
1.0
1.5
2.5
1.5
1.5
1.5
1.0
2.5
> 99+0
98+2
55
40
27
51
55
60
36
66
0+ > 99
96+4
87+13
76+24
> 99+0
0+ > 99
a Ratio determined by GC. b Combined isolated yield of 4a and 5a.
1. With increasing the amount of THF into the reaction mixture,
the formation of 5a also proportionately increased and the
reactions became cleaner as indicated by the combined isolated
yields of 4a and 5a. Interestingly, using a combination of
DMSO–THF (30+70) and 2.5 equiv. of sodium dimsylate (entry
8), 5a was the sole product, isolated in 66% yield. It was also
gratifying to note that 5a formed exclusively from the adduct 3
(Scheme 1; R = PhMe2Si, E1 = E2 = CO2Et) where the
elimination of a proton and dimethyl sulfide was favored over
the loss of a silyl group in a Peterson-type elimination. In
addition, one-pot olefination–alkylation protocol was devised
using 1.2 equiv. of trimethylsulfonium iodide and 2.5 equiv. of
sodium dimsylate, and quenching the reaction with alkyl halides
leading to functionalised vinyl silanes 5b–e in good yields as
shown in Scheme 2. It is worth mentioning that these type of
vinyl silanes are important intermediates in organic synthe-
ses5–8 and there has been no reported general access to
1,1-disubstituted vinyl silanes.9
At this stage we were not convinced whether the silyl
(PhMe2Si) substitution in 2a was responsible for this preferred
elimination over cyclopropanation. Therefore, the one-pot
protocol (olefination–alkylation) was attempted using a series
of arylidene malonates 2b–e. We were pleased to observe that
the above elimination process was general and furnished the
styrene derivatives 5f–i exclusively in moderate to good yields
as shown in Table 2. The poor yield of the styrene 5i could be
Scheme 1
† Electronic supporting information (ESI) available: general experimental.
See http://www.rsc.org/suppdata/cc/b2/b211279e/
Scheme 2
636
CHEM. COMMUN., 2003, 636–637
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Table 2 Preparation of substituted styrenes
Fig. 1
cation from Na to K. Fortunately, the reaction could be driven
in the desired direction to give styrene 5k albeit in poor yield by
the addition of MgBr2 into the reaction medium prior to the
addition of methyl iodide. The reaction yields with the
cyanoacetates 2f and 2g were modest possibly due to the
polymerisation of the substrates. However, the polymeric
materials being polar, the desired products could be isolated
very easily. The substrate with a phosphonate activating group
such as 2h gave exclusively the desired styrene derivative 5l in
50% yield by this method.
In conclusion, we have developed a novel application of
dimethylsulfonium methylide for the general preparation of not
readily accessible and synthetically valuable 1,1-disubstituted
vinyl silanes, and substituted styrene derivatives from easily
available activated olefins. This study also demonstrated that by
varying conditions, the reactions could be tuned in either
direction to give the vinyl silane or the cyclopropane ex-
clusively. In these reactions, dimethylsulfonium methylide (1)
acts as a synthetic equivalent of carbene anion 10 (Fig. 1). Since
convenient methods for the generation of substituted sulfur
ylides are known,12 the present methodology might be extended
for the preparation of highly substituted vinyl silanes and
styrene derivatives.
Entry
R
Substrate
Product
% Yield
1
2
3
4
Ph
2b
2c
2d
2e
5f
73
57
69
20
4-MeO-C6H4
4-Br-C6H4
4-NO2-C6H4
5g
5h
5i
due to the polymerization of the substrate 2e under the reaction
conditions, as was evident from the generation of a substantial
amount of colored polar material.‡ No cyclopropanation
product was observed in any of these cases.
Our next interest was to study the influence of activating
groups on the Michael acceptor 2. The silyl substituted
alkylidene cyanoacetate 2f was prepared and subjected under
similar protocol to give exclusively the desired vinyl silane 5j
(Table 3). Contrary to silyl substitution, the arylidene cyanoace-
tate 2g gave the desired product 5k along with a double
alkylation product 7b in a ratio of 6+4. The formation of 7b
could be explained as shown in Scheme 3. Due to the presence
of CN group, the negative charge could delocalise between C-2
and C-4 in 8.10 Methylation at C-2 gave the styrene derivative
5k while that at C-4 provided an intermediate 9. The latter in the
presence of excess base underwent allylic deprotonation, which
on isomerization11 followed by reaction with methyl iodide
yielded 7b. The cis-relationship between the Me and the Ar in
7b was confirmed by 1D-NOE study (7.5% NOE enhancement
was observed between olefinic proton and the C-2 Me). The
selectivity (5k vs. 7b) could not be improved by changing the
Note added in proof. b-Silylethyl sulfoxides having b-
carbonyl functionalities are known to give vinyl silanes. See ref.
13.
Notes and references
‡ Polar residue was not characterised.
Table 3 Effect of activating group on the one-pot olefination–alkylation
reaction
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X
R
Substrate Products Ratio 5/7 %Yield
CN
CN
CN
CN
PhMe2Si
2f
5j; 7a
5k; 7b
5k; 7b
5k; 7b
5l; 7c
> 99+0
28
4-MeO-C6H4 2g
4-MeO-C6H4 2g
4-MeO-C6H4 2g
64+36 60
65+35 55a
> 99+0
> 99+0
17b
50
P(O)(OEt)2 4-MeO-C6H4 2h
a Potassium dimsylate was used instead of sodium dimsylate. b MgBr2 was
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Scheme 3
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