Preparation of vinyl silyl ethers and disiloxanes via the silyl-heck reaction of silyl ditriflates

Article abstract of DOI:10.1021/ja407748z

Vinyl silyl ethers and disiloxanes can now be prepared from aryl-substituted alkenes and related substrates using a silyl-Heck reaction. The reaction employs a commercially available catalyst system and mild conditions. This work represents a highly practical means of accessing diverse classes of vinyl silyl ether substrates in an efficient and direct manner with complete regiomeric and geometric selectivity.

Full text of DOI:10.1021/ja407748z

Communication
pubs.acs.org/JACS
Preparation of Vinyl Silyl Ethers and Disiloxanes via the Silyl-Heck
Reaction of Silyl Ditriflates
Sara E. S. Martin and Donald A. Watson*
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States
S
* Supporting Information
ABSTRACT: Vinyl silyl ethers and disiloxanes can now
be prepared from aryl-substituted alkenes and related
substrates using a silyl-Heck reaction. The reaction
employs a commercially available catalyst system and
mild conditions. This work represents a highly practical
means of accessing diverse classes of vinyl silyl ether
substrates in an efficient and direct manner with complete
regiomeric and geometric selectivity.
Figure 1. Preparation of vinyl silyl ethers from alkenes.
method uses a commercially available catalyst system and
requires only catalytic amounts of iodide additives. When
combined with Hiyama−Denmark cross-coupling, this chem-
istry provides superior yields and regioselectivities in the
preparation of stilbene derivatives compared to direct Heck
arylation. Furthermore, by varying the nature of the quenching
reagent, this strategy allows the direct preparation of a wide
variety of vinylsilanes with tunable reactivity.
inylsilanes are ubiquitous reagents in organic synthesis,1 in
Vpart because their high utility is complemented by low
toxicity and high stability.2 Among vinylsilanes, those bearing
oxygen substitution at silicon are particularly useful, as these
reagents consistently provide superior reactivity compared to
their trialkylsilyl counterparts, especially when used in
Hiyama−Denmark cross-coupling3 or in Tamao−Fleming
oxidation.4
Though alkoxyvinylsilane reagents are highly useful, the
traditional methods to access them all carry significant
drawbacks, which can limit their utility. These reagents are
most often prepared either by silylation of a vinyl organo-
magnesium or -lithium reagent with an electrophilic silane5 or
through hydrosilylation of an alkyne.6 The first method requires
the corresponding organometallic reagents, which have limited
functional group compatibility, and as significantly, is often
derived from relatively complex starting materials (i.e., vinyl
bromides), which can take many steps to access. Similarly,
while hydrosilylation is milder in nature, the reaction requires
access to the corresponding alkynes, which also poses synthetic
challenges and have limited commercial availability. Indeed, the
limitations in accessing unsaturated silanes have been attributed
to be one of the primary reasons for the slow adoption of
Hiyama-type cross-coupling reactions compared to other cross-
couplings.7
Alkenes are widely abundant, stable starting materials.
However, to date, no direct methods exist to convert these
highly attractive starting materials into vinyl silyl ethers and
disiloxanes.8,9 A mild, functional group tolerant method to
achieve this conversion would greatly increase the synthetic
accessibility of oxygen-substituted vinylsilanes.
Herein we report the preparation of vinyl silyl ethers and
disiloxanes using silyl ditriflates (Figure 1). We show that these
reagents participate in the palladium-catalyzed silyl-Heck
reaction with terminal aryl-substituted alkenes and, upon
quenching with alcohol or water, provide trans-vinyl silyl ethers
in high yield as single regiomeric and geometric isomers. This
We recently reported a palladium-catalyzed synthesis of vinyl
and allyl trimethylsilanes from terminal alkenes and trimethyl-
silyl halides (X = Cl, I), which we believe proceeds through a
Heck-type mechanism.10 Although this method displayed good
functional group tolerance, it was limited to the preparation of
trimethylsilanes. We recognized that an analogous reaction that
allowed for the preparation of vinyl siloxyethers from simple
alkenes would significantly increase the utility of this silyl-Heck
reaction and allow facile access to this important class of
reagents. A possible entry into silyl ethers would involve the use
of dihalo or di(pseudo)halosilanes, however such substrates
have not previously been examined in Heck-type reactions.11
Our prior study demonstrated that Si-OTf bonds can
participate in silyl-Heck reactions in the presence of an iodide
additive.10 Thus, we began our studies by examining reaction of
dimethylsilyl ditriflate (Me2Si(OTf)2 (1)),12,13 using model
substrate 4-tert-butylstyrene and EtOH (Table 1). Our initial
reaction conditions mirrored those developed in the reactions
of trimethylsilyl halides (catalytic (COD)Pd(CH2TMS)2 (2)
and tBuPPh2 with stoichiometric LiI and Et3N at 60 °C). When
ethanol was added at the beginning of the reaction, modest
yield of the desired ethoxyvinylsilane 3a resulted (26%, Table 1,
entry 1). This reaction presumably proceeds via in situ
formation of Me2Si(OEt)(OTf). Although promising, attempts
to optimize these reaction conditions were not successful. In
contrast, simply waiting to add the alcohol until the end of the
reaction resulted in a dramatically improved yield of the desired
product (81%, entry 2). In this latter case, we assume that the
initially formed product is the corresponding dimethylvinylsilyl
triflate, which is then converted to the silyl ether upon addition
Received: July 30, 2013
© XXXX American Chemical Society
A
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Journal of the American Chemical Society
Communication
of the alcohol. Using this order of addition, commercially
available Pd2(dba)3 can also be used as the precatalyst with
equal success (entry 3). This result contrasts our earlier work
wherein Pd2(dba)3 was ineffective. Modest decreases in the
reaction temperature were tolerated without ill effect, but at
room temperature the reaction was sluggish (entries 4 and 5).
The reaction proved sensitive to the amount of 1 employed. A
slight excess (1.1 equiv) of 1 proved optimal, but additional
reagent rapidly eroded the yield (entry 6). As anticipated,
iodide was a critical additive in the reaction (entry 7). However,
only a catalytic amount was required and afforded superior
yields (entry 8).14 Unlike our prior work, both LiI and NaI can
be used with equal effect (entry 9). As NaI is both cheaper and
more readily handled, we continued our studies with this
additive. Finally, additional studies demonstrated that the
reactions were best conducted at 35 °C and that only 2.5 mol %
palladium was required to achieve quantitative yield (NMR).
With these conditions in hand, we investigated the scope of
the reaction (Table 2). On preparative scale (1−5 mmol), the
model product 3a was isolated in 92% yield as the trans-vinyl
silyl ether. A variety of other alcohols, including both secondary
and tertiary alcohols, can also be used to quench the reaction,
giving rise to a series of vinyl silyl ethers in similar isolated
yields (3b, 3c). When water was used to quench the reaction,
disiloxane 3d emerged in good isolated yield. In general, any of
these quenching methods can be used to prepare vinylsilanes
via this method, as demonstrated by the series of silanes 4−6
Table 1. Optimization of Silyl Ether Formation
temp
(°C)
Pd source
(mol %)
amount of 1
(equiv)
M+I−
(mol %)
yield by
entry
NMR (%)
a
1
2
3
60
60
60
2 (5)
2 (5)
1
1
1
LiI (100)
LiI (100)
LiI (100)
26
81
81
Pd2(dba)3
(2.5)
4
40
rt
Pd2(dba)3
(2.5)
1
LiI (100)
LiI (100)
LiI (100)
LiI (0)
78
22
24
6
5
Pd2(dba)3
(2.5)
1
6
40
40
40
40
35
Pd2(dba)3
(2.5)
1.5
1
7
Pd2(dba)3
(2.5)
8
Pd2(dba)3
(2.5)
1.1
1.1
1.1
LiI (5)
98
98
>99
9
Pd2(dba)3
(2.5)
NaI (5)
NaI (5)
10
Pd2(dba)3
(1.25)
a
EtOH added at start.
Table 2. Scope of Substrates for Silyl Ether and Disiloxane Formation
a
b
c
d
e
Isolated yields (average of two runs), 1 mmol scale unless otherwise noted. 5 mmol scale. 2.5 mol % Pd2(dba)3, 11 mol % tBuPPh2. 48 h. 50 °C.
f
60 °C.
B
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Journal of the American Chemical Society
Communication
(exceptions noted below). For simplicity, we elected to study
quenching with isopropanol and water in the remaining
examples. In all cases, only trans-1,2-disubstituted vinylsilanes
were observed. No trace of the cis-vinyl isomer, nor the 1,1-
disubstituted regioisomeric silane has been detected.
A wide variety of vinyl arenes also participate in the reaction.
Both electron-donating and electron-withdrawing ethereal
substrates generate products in high yields (5 and 6, Table
2). Dioxolane and silyl ether functionalities were well tolerated
(7−9), as were fluorides, chlorides, esters, and tertiary amines
(10−13). In general, substrates bearing electron-withdrawing
substituents were slower to react than their electron-rich
counterparts and required slightly elevated reaction temper-
ature and time. In the extreme, substrates bearing highly
electron-withdrawing groups, such as p-nitrostyrene (not
shown) were unreactive. Steric hindrance on the arene did
not adversely affect the reaction (14); however increased
substitution on the alkene was not tolerated using the current
catalyst (not shown).15
example, it is well known that direct Heck arylation of
electron-rich styrenes leads to a mixture of regioisomeric
products.20 Selectivity is particularly poor for triflate electro-
philes. For example, arylation of p-methoxystyrene with phenyl
triflate gives a 57:43 mixture of α and β products, which in our
hands were obtained in 81% yield (Scheme 1, top).21 In
Scheme 1. Silyl-Heck/Hiyama−Denmark vs Direct Heck
Reactions
Alkenes bearing heterocycles are also substrates. Silyl ether
15 was formed from 2-vinylbenzofuran in good yield, and the
reaction of N-tosyl-3-vinylindole led to vinylsilane 16 without
incident. Finally, the reaction of N-vinylcarbazole provided silyl
ether 17 in high yield. In the case of these heterocyclic
substrates, alcohol quench proved to be superior to those using
water. In the case of both 15 and 17, water quench led to
complex mixtures of products.
This silyl-Heck protocol is also compatible with a range of
more complex vinylic substrates. For example, vinylferrocene
can be silylated in near quantitative yield to give redox-active
vinylsilanes 18a and 18b. We anticipate that these products will
be highly useful in the preparation of topologically defined
redox probes.16 Similarly, 4-vinylbenzocyclobutene is also an
excellent substrate. Isopropyl silyl ether 19a was isolated in 91%
yield. Water quench led to the formation of divinyldisiloxane
bis-benzocyclobutene (19b) in similar yield. This latter product
is the key monomer of Cyclotene photoresist resins.17
Bis-functionalized silyl boronic esters 20a and 20b were
readily prepared from (4-vinylphenyl)pinacolboronic ester. In
this reaction, no C−B bond activation was observed. These
products provide a lynch-pin substrate for orthogonal Suzuki
and Hiyama−Denmark coupling reactions.18
As a final example of a complex substrate, we examined the
preparation of estradiol-derived vinylsilanes 21a and 21b. As in
the previous examples, these complex materials can be prepared
without incident in high yield with either isopropanol or water
quench. Not only do these results demonstrate that highly
complex substrates are compatible with the silyl-Heck reaction
conditions, but the products for this and similar trans-
formations will be highly useful in preparing bimolecular
conjugates.
contrast, Hiyama−Denmark coupling of vinyl silyl ethers 5a
and 5b proceeded in 95% and 84% yield, respectively, to give
exclusively stilbene product 23 (Scheme 1, bottom).22 As 5a
and 5b are obtained in high yields as single isomers from p-
methoxystyrene in the silyl-Heck reaction, this two-step
protocol is vastly superior in overall yield and avoids the
difficult separation of regioisomeric products.
In addition, because of the intermediacy of the vinylsilyl
triflate, this strategy provides a divergent approach to
differentially substituted vinylsilanes. For example, quenching
with allyl- or benzylmagnesium chloride leads to the
corresponding dimethylvinylsilanes 25 and 26 in high yields
(Scheme 2). Allyl- and benzylsilanes have proven highly useful
in a variety of applications,3c,4,23 and this method provides a
convenient method for accessing these materials via the silyl-
Heck reaction.
In summary, we have developed a novel method to generate
reactive and versatile vinyl silyl ethers and disiloxanes from aryl-
substituted alkenes and related starting materials. This method
Scheme 2. Preparation of Diverse Vinylsilanes
We also have begun to explore the scope of the groups on
the silyl ditriflate. We were pleased to find that diethylsilyl
ditriflate is also an excellent silylating agent. Under the
optimized reaction conditions, similar yields were observed
for diethylvinylsilanes with this reagent. For example, 4-tert-
butylstyrene can be silylated in 88% yield, after isopropanol
quench (eq 1).19 This strategy will allow for tuning of the
reactivity of the vinylsilane products.
The formation of vinyl silyl ethers presented herein has
numerous advantages. First, the fact that only a single
regiomeric and geometric isomer is obtained provides a
significant advantage over competing technologies. For
a
1.25 mol % Pd2(dba)3, 5.5 mol % tBuPPh2, 1.1 equiv Me2Si(OTf)2, 5
mol % Nal, Et3N, PhMe, 35 °C.
C
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Journal of the American Chemical Society
Communication
(9) As this manuscript was in preparation, a report appeared
demonstrating the preparation of predominately cis-vinyl silyl ethers
from terminal alkenes using iridium-catalyzed hydrosilylation and a
sacrificial oxidant: Cheng, C.; Simmons, E. M.; Hartwig, J. F. Angew.
Chem., Int. Ed. 2013, 52, 8984−8989.
(10) McAtee, J. R.; Martin, S. E. S.; Ahneman, D. T.; Johnson, K. A.;
Watson, D. A. Angew. Chem., Int. Ed. 2012, 51, 3663−3667.
(11) Tanaka has demonstrated the oxidative addition of Pt(0)
complexes to dichlorosilanes in stoichiometric reactions: Yamashita,
H.; Tanaka, M.; Goto, M. Organometallics 1997, 16, 4696−4704.
(12) Matyjaszewski, K.; Chen, Y. L. J. Organomet. Chem. 1988, 340,
7−12.
exhibits broad functional group tolerance, and products are
generated in good to excellent isolated yields and as single
regiomeric and geometric isomers. The reaction proceeds with
readily accessible reagents and an inexpensive, commercially
available catalyst. Not only does this reaction dramatically
expand the utility of the silyl-Heck reaction by allowing access
to a wide variety of highly useful vinyl silyl ethers and related
reagents, for the first time, it demonstrates that silane
(bis)electrophiles can be used in a Heck-type process. Future
studies will be directed toward expanding this transformation to
other classes of alkenes and related molecules.
(13) This reagent is easily prepared from the reaction of neat
Ph2SiMe2 and TfOH. It can be stored under nitrogen indefinitely after
removal of the resulting PhH under vacuum, or used directly without
diminished yield in the silyl-Heck reaction. See Supporting
Information.
(14) We believe iodide additives result in in situ generation of Si-I
species, which enable oxidtive addition: Olah, G. A.; Narang, S. C.;
Gupta, B. G. B.; Malhotra, R. J. Org. Chem. 1979, 44, 1247−1251.
(15) Terminal alkenes bearing allylic hydrogen atoms are also
reactive but give poor allyl vs vinyl selectivity. See Supporting
Information for an example.
(16) Gietter, A. A. S.; Pupillo, R. C.; Yap, G. P. A.; Beebe, T. P.;
Rosenthal, J.; Watson, D. A. Chem. Sci. 2013, 4, 437−443.
(17) (a) Gros, W. A. Benzocyclobutene-based Die Attach Adhesive
Compositions. U.S. Patent 4759874, 1988. (b) Kirchhoff, R. A.; Bruza,
K. J. Prog. Polym. Sci. 1993, 18, 85−185.
(18) Lim, D. S. W.; Anderson, E. A. Org. Lett. 2011, 13, 4806−4809.
(19) Some reactivity was also observed with diisopropylsilyl ditriflate.
However, the yields remain low with the present catalyst system.
(20) (a) Fristrup, P.; Le Quement, S.; Tanner, D.; Norrby, P.-O.
Organometallics 2004, 23, 6160−6165. (b) Oestreich, M., The
Mizoroki−Heck Reaction; John Wiley & Sons: Chichester, UK, 2008.
(21) With the use of phenyl iodide, selectivity is only marginally
better in this reaction (90:10 β:α).
ASSOCIATED CONTENT
* Supporting Information
Experimental procedures and spectral data. This material is
available free of charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
dawatson@udel.edu
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Mr. Scott Shuler is thanked for assistance. The University of
Delaware (UD), the NSF (CAREER CHE1254360), and the
Research Corporation (Cottrell Scholars Program) are grate-
fully acknowledged. S.E.S.M. acknowledges graduate fellowship
support from NIH 5T32 GM 08550-16. Data were acquired at
UD on instruments obtained with the assistance of NSF and
NIH funding (NSF CHE0421224, CHE1229234, and
CHE0840401; NIH P20 GM103541 and S10 RR02692).
Dedicated to Professor Larry E. Overman on the occasion of
his 70th birthday.
(22) (a) Denmark, S. E.; Sweis, R. F. Org. Lett. 2002, 4, 3771−3774.
(b) Denmark, S. E.; Regens, C. S. Tetrahedron Lett. 2011, 52, 2165−
2168.
(23) Bennetau, B., Benzylsilanes. In Science of Synthesis; Fleming, I.,
Ed.; Thieme: Stuttgart, 2002; Vol. 4, pp 825−836.
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D
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