Calcium-catalyzed direct coupling of alcohols with organosilanes

Article abstract of DOI:10.1002/ejoc.201100231

A calcium-catalyzed direct substitution of π-activated alcohols with different organosilanes under very mild reaction conditions is presented. The high reactivity of the calcium catalyst allows efficient conversion of secondary and tertiary allylic, secondary benzylic, and tertiary propargylic alcohols with allyltrimethylsilane at room temperature. Furthermore, the first direct substitution of an alcohol with (E)- as well as (Z)-alkenylsilanes was achieved under mild reaction conditions. Copyright

Full text of DOI:10.1002/ejoc.201100231

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201100231
Calcium-Catalyzed Direct Coupling of Alcohols with Organosilanes
Vera J. Meyer[a] and Meike Niggemann*[a]
Keywords: Calcium / Silanes / Direct substitution / Alcohols / C–C coupling
A
calcium-catalyzed direct substitution of π-activated
alcohols with allyltrimethylsilane at room temperature.
Furthermore, the first direct substitution of an alcohol with
(E)- as well as (Z)-alkenylsilanes was achieved under mild
reaction conditions.
alcohols with different organosilanes under very mild reac-
tion conditions is presented. The high reactivity of the cal-
cium catalyst allows efficient conversion of secondary and
tertiary allylic, secondary benzylic, and tertiary propargylic
reactions, are substantially reduced. The direct addition of
allyltrimethylsilane to alcohols in the presence of Lewis[4]
or Brønsted[5] acids has been investigated by other groups.
However, many of these transformations suffer from signifi-
cant drawbacks such as harsh reaction conditions, pro-
longed reaction times, and low functional group compati-
bility. In further pursuit of our efforts towards the develop-
ment of main group metal-catalyzed reactions for organic
synthesis, as an alternative to traditionally used transition-
metal-catalyzed transformations, we herein report the direct
substitution of π-activated alcohols with silicon-based carb-
anion surrogates.
Introduction
Precious metals, playing a critical role in many homoge-
neously catalyzed reactions, are becoming increasingly rare
and consequently more expensive as we use up natural re-
sources. Therefore, the search for alternative catalysts is
nowadays of more significance. The potential application of
early main group metals as catalysts has remained a widely
underexplored research field, despite the apparent ecologi-
cal and economical benefits. Among other alkaline earth
metals, calcium seems to be an ideal main group metal cata-
lyst,[1] as it is essentially free of toxicity, very cheap, and the
fifth most frequent element of the earth crust. We recently
reported a novel calcium-based, highly Lewis acidic catalyst
system for the dehydration of benzylic, allylic, and propar-
gylic alcohols and their subsequent reaction with nucleo-
philic arenes under very mild reaction conditions.[2,3] We
have now turned our attention towards catalytic C–C bond
formation with water-tolerant organometallic reagents. The
general utility of unsaturated organosilicon compounds as
carbanion surrogates is well recognized. Numerous scien-
tific efforts devoted to the exploration of these compara-
tively stable and environmentally benign organometallic
reagents have led to their establishment as a valuable instru-
ment in the synthetic tool box. The use of alcohols as elec-
trophilic coupling partners in C–C bond-formation reac-
tions with these very mild organometallic reagents appears
beneficial in several ways. Silanol is formed as the only by-
product during the reaction. The transformation of the hy-
droxy group into a better leaving group such as the corre-
sponding halide, carboxylate, carbonate, phosphate, or re-
lated compounds is unnecessary. Consequently, overall salt
loads, being a common accompaniment of metal organic
Results and Discussion
Initially, we attempted the allylation of methyl cinnamyl
alcohol (1) with allyltrimethylsilane (2) in the presence of
our calcium-based catalyst system consisting of Ca(NTf2)2
(5 mol-%) and Bu4NPF6 (5 mol-%). The reaction proceeded
smoothly at room temperature in dichloromethane to give
the desired allylated product after 1 h as a 2.7:1 mixture of
regioisomers 3a/3b in 76% yield. To improve the regioselec-
tivity and the yield of the transformation, we investigated
the effect of various additives (Table 1). In the presence of
tetrabutylammonium hexafluorosilicate or tetraphenylbor-
ate, the reactivity of the catalyst was inhibited (Table 1, En-
tries 2 and 3). The tetrapentafluorophenylborate anion
based additive increased the yield at the expense of regiose-
lectivity (Table 1, Entry 4). In presence of the hexafluo-
roantimonate salt, the outcome of the reaction was compar-
able to that of the initial attempt with hexafluorophosphate
(Table 1, Entry 5 vs. 1). The best results were obtained by
using tetrabutylammonium tetrafluoroborate (Table 1, En-
try 6). In an earlier publication, we already discussed the
role of the additive as a precursor for the formation of the
catalytic species by anion exchange.[6] Unfortunately, the
formation of the catalytically active CaNTf2BF4 species
proved less efficient under the reaction conditions starting
[a] Institute for Organic Chemistry, RWTH Aachen University,
Landoltweg 1, 52074 Aachen, Germany
Fax: +49-241-80 92127
E-mail: Niggemann@oc.rwth-aachen.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100231.
Eur. J. Org. Chem. 2011, 3671–3674
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3671

V. J. Meyer, M. Niggemann
SHORT COMMUNICATION
from commercially available Ca(BF4)2 and Bu4NNTf2 nation reaction occurred during the conversion of tertiary
(Table 1, Entry 7). As for previously described calcium-cat- propargylic alcohols. Fortunately, the use of a greater excess
alyzed reactions, dichloromethane proved to be the most of the nucleophile (5 equiv.) was sufficient to suppress the
suitable solvent for the allylation of alcohols. The transfor- undesired elimination to an extent that moderate yields of
mation is incomplete and stops after the intermediary for- the allylated products were obtained (Table 2, Entries 10–
mation of ether 3c in stronger coordinating, ethereal sol- 12). As for previously described calcium-catalyzed transfor-
vents (Table 1, Entries 8 and 9).[6] The reaction in toluene,
giving only slightly poorer results than those obtained in
dichloromethane, represents a potential alternative (Table 1,
Entry 10) where non-halogenated solvents are mandatory.
Table 2. Allylation of different alcohols with allyltrimethylsilane
(2).[a]
Table 1. Optimization of the reaction conditions.[a]
Entry
CaX2
Additive
3a/3b/3c[b]
t
[h]
Yield[c]
[%]
1
2
3
4
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Bu4NPF6
(Bu4N)2SiF6
Bu4NBPh4
PhMe2NH
B(C6F5)4
2.7:1:0
–
–
1
16
16
1
76
–
–
2:1:0
98
5
6
7
Ca(NTf2)2
Ca(NTf2)2
Ca(BF4)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Ca(NTf2)2
Bu4NSbF6
Bu4NBF4
Bu4NNTf2
Bu4NBF4
Bu4NBF4
Bu4NBF4
Bu4NBF4
2.7:1:0
2.7:1:0
2.4:1:0.3
4:1:7
1:0:5
2.7:1:0
2.7:1:5
1
1
1
1
1
1
1
75
91
69
23
9
84
30
8[d]
9[e]
10[f]
11[g]
[a] CaX2 (5 mol-%) and the additive (5 mol-%) were added at room
temperature to allyl alcohol (0.5 mmol) and allylsilane
1
2
(1.5 mmol) in CH2Cl2 (1 mL), and the mixture was stirred for the
time indicated. [b] Ratio determined by GC analysis. [c] Isolated
yield. [d] Reaction run in Et2O. [e] Reaction run in THF. [f] Reac-
tion run in toluene. [g] Reaction run in hexane.
To explore the generality and scope of the reaction, a
series of different alcohols was allylated under the opti-
mized reaction conditions (Table 2). The transformation of
secondary allylic alcohols with 2 afforded the desired prod-
ucts in good yields after 1 h at room temperature. The ad-
dition of the allyl anion surrogate occurred regioselectively
in the case of alcohols 4, 6, and 10 (Table 2, Entries 1, 3
and 4), and only product 9 was obtained as a 6.2:1 mixture
of regioisomers 9a/9b (Table 2, Entry 3; Supporting Infor-
mation). In analogy with previously investigated calcium-
catalyzed reactions,[3,6] tertiary allylic alcohol 12 reacted
with complete isomerization of the double bond to yield
product 13. The allylation of secondary benzylic alcohols
gave the desired products in good yields and selectivities
(Table 2, Entries 6–9). The transformation of tertiary benz-
ylic alcohols was hampered by a competing background re-
action, affording the corresponding olefins by irreversible
elimination of H2O. Therefore, the desired reaction prod-
[a] Ca(NTf2)2 (5 mol-%) and Bu4NBF4 (5 mol-%) were added at
room temperature to the alcohol (0.5 mmol) and allylsilane 2
(1.5 mmol) in CH2Cl2 (1 mL), and the mixture was stirred for the
time indicated. [b] Isolated yield. [c] Mixture of regioisomers 6.2:1
ucts were formed in unsatisfactory yields. The same elimi- (see Supporting Information). [d] 2.5 mmol of 2 was used.
3672 Eur. J. Org. Chem. 2011, 3671–3674
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Calcium-Catalyzed Direct Coupling of Alcohols with Organosilanes
mations, primary alcohols as well as aliphatic alcohols that tions,[8] readily reacted with alcohol 20 to provide desired
do not bear a π-activating moiety were unsuitable substrates product (Z)-31, again with complete retention of the double
even at elevated temperatures.
bond geometry.
Despite the prosperity of the commonly used allylsi-
lanes,[7] the potential of other unsaturated organosilicon
compounds such as vinylsilanes received only little atten- Conclusions
tion.[8] This is undoubtedly due to the much lower inherent
In summary, we have developed a new and efficient cal-
nucleophilicity of these species. Therefore, we were very
pleased to find that vinylsilanes, such as 28, were suitable
nucleophilic coupling partners for the calcium-catalyzed
substitution of alcohols under our optimized reaction con-
ditions (Table 3). Due to the lower reactivity of these si-
lanes, the reaction of the intermediary formed carbocation
with the silyl nucleophile is assumed to be comparatively
slow. Thus, only alcohols that provide well-stabilized carbo-
cations were suitable for this transformation, as they have
a lower propensity to partake in undesired side reactions
such as eliminations and polymerizations. Electron-rich sec-
ondary benzylic alcohols 18, 4, and 20 reacted readily with
(E)-2-phenyl-1-trimethylsilylethylene [(E)-28] to afford de-
sired products 29, 30, and (E)-31 within 1 h at room tem-
perature in good to moderate yields with complete retention
of the double bond geometry (Table 3, Entries 1–3). To the
best of our knowledge this is the first time that an alcohol
was demonstrated to react with an alkenylsilane under con-
ditions below 80 °C. Furthermore, vinylsilane (Z)-28, which
has shown no nucleophilicity in previously described reac-
cium-catalyzed direct coupling of π-activated alcohols with
different types of silyl-based carbanion surrogates under
very mild reaction conditions. The high reactivity of the
calcium catalyst allows efficient conversion of secondary
and tertiary allylic, secondary benzylic, as well as tertiary
propargylic alcohols with allyltrimethylsilane. Furthermore,
the first direct substitution of an alcohol with (E)- as well
as (Z)-alkenylsilanes was achieved under mild reaction con-
ditions. Typical reactions proceed at room temperature,
with no added strong acids or bases, and special pre-
cautions for exclusion of moisture or air are not unneces-
sary.
Experimental Section
Typical Procedure: To a solution of the alcohol (0.5 mmol) and the
organosilane (1.5 mmol) dissolved in dichloromethane (1 mL) was
added Bu4NBF4 (5 mol-%) and Ca(NTf2)2 (5 mol-%) at room tem-
perature, and the mixture was stirred until conversion of the
alcohol was complete (monitored by TLC and/or GC). For isola-
tion of the product, sat. NaHCO3 solution (5 mL) was added, the
aqueous phase was extracted with dichloromethane (2ϫ). The com-
bined organic extracts were dried with Na2SO4 and concentrated
in vacuo, and the crude product was purified by column
chromatography.
Table 3. Alkenylation of alcohols.[a]
Supporting Information (see footnote on the first page of this arti-
1
cle): Experimental procedures and copies of the H NMR spectra
of all products.
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Received: February 21, 2011
Published Online: March 29, 2011
3674
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