Tunable cross coupling of silanols: Selective synthesis of heavily substituted allenes and butadienes

Article abstract of DOI:10.1021/ja3070717

1,3-Dienyl-2-silanols with a wide range of substitution patterns are readily obtained by palladium-catalyzed silaboration of 1,3-enynes followed by Suzuki-Miyaura cross coupling with aryl bromides. Subsequent Hiyama-Denmark cross coupling with aryl iodides provides either 1,3- or 1,2-dienes in high yields. The site selectivity can be fully controlled by the choice of activator used in the coupling reaction. In the presence of strong bases such as NaOt-Bu, KOt-Bu, and NaH, clean formation of 1,2-dienes takes place via allylic rearrangement. In contrast, stereo- and site-selective formation of tetra- and trisubstituted 1,3-dienes results from use of Ag₂O and Bu ₄NF·3H₂O, respectively, as activators. Under microwave heating at 100 °C the base-mediated cross couplings are largely accelerated and are completed within one hour or less. The ratio of diastereomeric allenes varies depending on the substitution pattern of the silanol and ranges from >99:1 to 52:48.

Full text of DOI:10.1021/ja3070717

Article
pubs.acs.org/JACS
Tunable Cross Coupling of Silanols: Selective Synthesis of Heavily
Substituted Allenes and Butadienes
Hui Zhou and Christina Moberg*
KTH Royal Institute of Technology, School of Chemical Science and Engineering, Department of Chemistry, Organic Chemistry,
SE 100 44 Stockholm, Sweden
S
* Supporting Information
ABSTRACT: 1,3-Dienyl-2-silanols with a wide range of
substitution patterns are readily obtained by palladium-catalyzed
silaboration of 1,3-enynes followed by Suzuki−Miyaura cross
coupling with aryl bromides. Subsequent Hiyama−Denmark
cross coupling with aryl iodides provides either 1,3- or 1,2-
dienes in high yields. The site selectivity can be fully controlled
by the choice of activator used in the coupling reaction. In the
presence of strong bases such as NaOt-Bu, KOt-Bu, and NaH,
clean formation of 1,2-dienes takes place via allylic rearrange-
ment. In contrast, stereo- and site-selective formation of tetra- and trisubstituted 1,3-dienes results from use of Ag2O and
Bu4NF·3H2O, respectively, as activators. Under microwave heating at 100 °C the base-mediated cross couplings are largely
accelerated and are completed within one hour or less. The ratio of diastereomeric allenes varies depending on the substitution
pattern of the silanol and ranges from >99:1 to 52:48.
Scheme 1. Palladium-Catalyzed Cross Coupling of 1,3-
Dienyl-2-silanols
INTRODUCTION
■
Palladium-catalyzed cross-coupling reactions have emerged as
efficient synthetic tools for the construction of carbon−carbon
bonds. Among the various available methods, Hiyama−
Denmark reactions are particularly attractive due to the low
cost, low toxicity, and high chemical stability of the silicon
compounds used as cross-coupling partners.1 Cleavage of the
strong carbon−silicon bond requires the presence of an
activating agent for transmetalation to occur. With the
introduction of organosilanols,2 a viable alternative to the
originally used fluoride activation became available, allowing the
reactions to be performed under mild conditions in the
presence of base.3
(butadienes)8 and γ-coupled products (allenes),9 we decided
to examine the influence of different activators on the coupling
reaction.
Organosilanols are available by several methods.4 Although a
variety of silanols, including aryl-, heteroaryl-, alkenyl-, alkynyl-,
and allylsilanols, have been prepared, the substrate scope is still
limited.1,3,5 To allow for methodological extension, construc-
tion of new types of silanol substrates is important. During our
current study, substrates containing 1,3-dienyl-2-silanol struc-
tural elements6 were subjected to cross couplings with aryl
iodides. Although coupling reactions of vinyl- and allylsilanols
have been studied, no reports on reactions using these
substrates, which contain both vinyl- and allylsilanol fragments,
are available. Denmark and co-workers have demonstrated that
vinylsilanols react with retention of olefin configuration2b and
that allylic silanolate salts in the presence of dibenzylidene-
acetone (dba)-derived palladium catalysts react with aryl
bromides to yield γ-coupled products with high site selectivity.7
The present 1,3-dienyl-2-silanol substrates were thus expected
to be able to react as alkenyl- as well as allylsilanols (Scheme 1).
In consideration of the importance of both α-coupled
RESULTS AND DISCUSSION
■
Silaboration of Enynes. The required 1,3-dienyl-2-silanols
were prepared starting from 1,3-enynes, which were readily
obtained by Sonogashira couplings of vinyl bromides and
alkynes. Silaborations of unsaturated organic compounds
catalyzed by group 10 metal complexes10 are known to provide
access to adducts containing boron and silicon functions with
orthogonal reactivity, thereby offering the opportunity for
sequential introduction of functionality.11 Although additions of
silylboranes to alkynes have been extensively studied12 and
shown to generally proceed in a cis manner,13 few examples of
silaborations of 1,3-enynes are known.14 Previous studies in our
group demonstrated that the palladium-catalyzed addition of
(dimethylphenylsilyl)pinacolborane to E- and Z-dodec-5-en-7-
Received: July 19, 2012
Published: September 5, 2012
© 2012 American Chemical Society
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yne proceeds with high site selectivity and that high yields of
the products obtained by exclusive addition to the alkyne
function are obtained.15 To allow for further elaboration of the
primarily obtained products, a silyl function containing a
heteroatom is required. We were therefore pleased to find that
silaborations of enynes 1a−h employing the more reactive
(chlorodimethylsilyl)pinacolborane16 proceeded in the pres-
ence of Pd(0), obtained by in situ reduction of Pd(acac)2 with
DIBAL-H, and PEt3 in toluene at room temperature (Scheme
2). Addition of isopropanol and pyridine to the primarily
Table 1. Suzuki−Miyaura Cross-Coupling Reaction of 2 with
a b
,
Aryl Bromides
Scheme 2. Palladium-Catalyzed Silaboration of Enynes
a
Unless stated otherwise, all reactions were carried out using
Pd(PPh3)4 (11.6 mg, 10 mol %), K2CO3 (67.5 mg, 5.0 equiv), 2
(0.1 mmol), and aryl bromide (0.12 mmol, 1.2 equiv) in toluene/
EtOH/H2O (1.2/0.4/0.4 mL) at 80 °C under nitrogen for 24 h. Yields
b
refer to isolated yields after chromatography. 1-Bromonaphthalene as
starting material.
formed products gave the stable isopropoxy derivatives 2a−h,
which could be isolated by chromatography in 50−73% yields.
Products with a cis relationship between the silicon and boron
functions, and with the configuration of the original olefinic
bond unaffected by the addition, were obtained. The
constitutional isomers having the silyl group at the internal
position were obtained as main products, in all reactions except
that involving 1-phenyl-substituted enyne 1d in ratios of >96:4.
Suzuki−Miyaura Cross-Coupling Reactions. As ex-
pected, Suzuki−Miyaura cross couplings with a variety of aryl
bromides, containing electron-donating as well as electron-
attracting substituents, employing Pd(PPh3)4 as catalyst
resulted in the arylated products 3, with the isopropoxy
group on silicon converted to a hydroxyl group and with
unchanged configuration of the nonarylated olefinic bond.
Single stereoisomers were obtained in high yields after
chromatographic purification (Table 1). Even the sterically
crowded compound 3ag was obtained in 90% yield via coupling
with 1-bromonaphthalene.
To understand the reason for the unexpected hydrolysis of
the alkoxysilane,17 the isopropoxy derivative of 3aa, prepared in
moderate yield by Suzuki−Miyaura cross coupling of 1a with
bromobenzene in the presence of Pd(OAc)2, (S)-Phos, K3PO4,
and H2O (7 equiv) in toluene,11 was treated with aqueous
K2CO3 under the conditions used for the coupling reaction.
Under these conditions no hydrolysis was, however, observed.
Under the same conditions but with added tetrakis-
(triphenylphosphine)palladium, the silanol and the unreacted
isopropoxysilane were isolated in a ratio of 0.4:1. It is possible
that some intermediate formed in the reaction more efficiently
catalyzes the hydrolysis.
Activation by Base. We first studied the effect of using
strong base as activator. A variety of bases, such as NaH, NaOt-
Bu, and KOt-Bu, promoted the reaction of 3 with aryl iodides,
resulting in formation of 1,2-dienes 4 (see Table 2), thus
a
Table 2. Influence of CuI on Cross Coupling of 3aa
b
entry
R
additive
product
yield (%)
1
2
3
4
OCH3
NO2
4aaa
4aab
4aaa
4aab
84
23
92
52
OCH3
NO2
CuI
CuI
a
Reaction conditions: Pd2(dba)3·CHCl3 (5 mol %), CuI (1.0 equiv),
NaOt-Bu (2.0 equiv), 3aa (0.036 mmol), and iodobenzene (0.043
mmol) in toluene (0.5 mL) under nitrogen. Yields refer to isolated
yields after chromatography.
b
demonstrating that under these conditions substrates 3 react as
allylsilanes.7 No 1,3-dienes were present in the reaction
mixtures. The initial studies were performed on the cross
coupling of 3aa with 4-methoxyiodobenzene and 4-nitro-
iodobenzene in the presence of Pd2(dba)3·CHCl3 using NaOt-
Bu as activator (Table 2). A high yield, 84%, of allene 4aaa was
obtained after 48 h at 60 °C from the reaction with 4-
methoxyiodobenzene (entry 1). In contrast, use of electron-
poor 4-nitroiodobenzene resulted in merely 23% yield of the
product (entry 2). CuI has proven to have a beneficial effect on
palladium-catalyzed couplings of unreactive silanols.18 We
Organosilanol-Based Cross-Coupling Reactions. For
the subsequent coupling of the 1,3-dienyl-2-silanols 3 with aryl
iodides, the influence of different activators was evaluated. To
our surprise, we found that product formation was entirely
dependent on the choice of activating agent.
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indeed found that addition of the copper salt increased the
reactivity and provided the products in higher yields (92 and
52%, respectively, entries 3 and 4). We therefore decided to
include the addition of CuI into our standard conditions.
To avoid the long reaction times needed for full conversion
to product, we attempted to run the reactions at a higher
temperature, 100 °C. This did, however, result in reduced yield
due to Pd black formation (entry 2). Instead, we decided to use
microwave conditions, which have been shown to result in
largely reduced reaction times in a variety of palladium-
catalyzed cross-coupling reactions,19 including reactions with
alkoxysilanes.20 We were pleased to find that the time required
for the reaction of 3aa with 4-iodoanisole was dramatically
shortened, and the reaction could be carried out in only 20 min
at 100 °C (Table 3, entry 5), as compared to 48 h under
conventional heating at 60 °C, with unaffected yields of product
4aa.
pinacolborane to (Z)-non-2-en-4-yne followed by the Suzuki−
Miyaura coupling with bromobenzene. The two diastereomers
of 4aaa were however obtained in a ratio of 61:39, i.e., similar
to that observed from 3aa, although in lower yield (45%).
We next subjected pentasubstituted dienylsilanols 3f−h to
the same reaction conditions (Table 6). High yields of coupling
products were observed, except in the reaction with electron-
poor 4-nitroiodobenzene (entry 5). Excellent diastereoselectiv-
ities were observed in reactions with silanols 3g and 3h having
the olefinic groups incorporated in six- and seven-membered
rings, respectively. This procedure thus provides access to
tetrasubstituted allenes as essentially pure diastereomers
(entries 2−7). In contrast, from the reaction of cyclopentene
derivative 3f with 4-iodoanisole, a mixture of diastereomers was
obtained.
Aryl bromides have previously been successfully used as
electrophiles in coupling reactions with vinyl- as well as
allylsilanols.1 Reaction of silanol 3aa with 4-methoxybromo-
benzene in the presence of Pd2(dba)3 resulted in the desired
product, albeit in poor yield, at 60 °C as well as under
microwave conditions at 100 °C (Table 7). Aryl bromides
evidently exhibit insufficient reactivity toward the present
silanols.
Table 3. Optimization of Conditions for Cross Coupling of
a
3aa with 4-Iodoanisole
Activation by Fluoride. Attempted use of CsF as activator
resulted in low conversion of starting material, and only a
1
minor amount of coupling product was observed by H NMR
spectroscopy. No allene was detected in the mixture. Bearing in
mind that the reaction has been shown to proceed via
formation of a disiloxane,21 the reluctance of 3 to form this type
of sterically congested intermediate may provide an explanation
for its failure to react. In the presence of Bu4NF·THF (∼5 wt %
H2O) or Bu4NF·3H2O clean protiodesilylation22 occurred to
yield trisubstituted dienes 5aa and 5b, with retained
configuration of the two olefinic bonds (97 and 98% yields,
respectively, Scheme 4). No allenes were observed. As
expected, products 5 were also obtained in the absence of
iodoarene and palladium complex but under otherwise identical
reaction conditions.
b
entry
conditions
temperature (°C)
time
48 h
yield (%)
1
2
3
4
5
Δ
Δ
MW
MW
MW
60
100
60
92
85
40
66
90
40 h
20 min
20 min
20 min
80
100
a
Reaction conditions: Pd2(dba)3·CHCl3 (5 mol %), CuI (1.0 equiv),
NaOt-Bu (2.0 equiv), 3aa (0.036 mmol), and 4-iodoanisole (0.043
mmol) in toluene (0.5 mL) under nitrogen. Yields refer to isolated
b
yields of diastereomeric mixtures after chromatography.
An alternative sequence for the preparation of compounds 5
starting from enynes 1 and consisting of hydroboration/
Suzuki−Miyaura coupling would lead to mixtures of constitu-
tional isomers since noncatalyzed hydroboration of the enyne
suffers from low site selectivity.23 The present procedure
therefore constitutes a superior route to compounds 5.
Activation by Silver Oxide. In contrast to the use of fluoride
as activator, use of a stoichiometric amount of silver(I) oxide,
introduced as coupling promotor by Hiyama and co-workers,24
resulted in overall diarylation of the alkyne function (Table 8).
The reactions proved to exhibit high stereoselectivity.
Compounds 6, with a cis relationship of the aryl groups,
were obtained as major products, along with varying amounts
of the trans isomers. The configuration of the nonarylated
olefinic bond was preserved during the reaction. In contrast to
reactions promoted by base, attempted reaction of sterically
hindered naphthyl-substituted substrate 3ag with 4-iodoanisole
resulted in no product (entry 4). Tri- and tetraarylated 1,3-
butadiene derivatives were also effectively obtained using 3c−
3e and differently substituted iodobenzenes (entries 5−9). This
procedure thus constitutes a convenient method for the
preparation of heavily substituted dienes with controlled site
and stereochemistry.
The substrate range of the reaction was examined under
these optimized conditions. Trisubstituted arylallenes were
obtained as the sole products from tetrasubstituted silanols 3a−
3e (Table 4). High yields were observed, except in a reaction
involving 4-nitroiodobenzene (entry 5) and in the reaction of
sterically crowded 3ag with 4-iodoanisole (entry 6). 1,1-
Diphenyl-substituted silanols 3d and 3e required an extended
reaction time of 60 min but gave high yields of products
(entries 9 and 10). The diastereomeric ratios were, however,
low, ranging from about 1:1 to 7:3.
The distribution of diastereomers proved to be essentially
insensitive to the reaction conditions. Thus, reactions of 3aa
with 4-methoxyiodobenzene at room temperature, 60 °C, and
100 °C, resulted in similar diastereomeric ratios (dr, Table 5).
The presence of different ligands also proved to have a minor
influence on the diastereomeric ratio of the product (see Table
S1 of the Supporting Information); use of Pd2(dba)3 together
with aryl- and alkylphosphines as well as an imidazoline carbene
ligand resulted in essentially no change in product ratios,
although the yields were somewhat affected (55−95% as
compared to 87% in the absence of ligand).
Finally, the influence of a sterically bulky silanol group on the
product ratio was studied by employing the diphenylsilanol
analogue of 3aa, 3i, as substrate. This compound was obtained
analogously to 3aa by the addition of (chlorodiphenylsilyl)-
Heating under microwave conditions has previously been
shown to have no effect on Ag2O mediated coupling of
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a
Table 4. Cross Couplings of 3a−3e with Aryl Iodides Using Base as Activator
a
Unless stated otherwise, the reactions were carried out using Pd2(dba)3·CHCl3 (5 mol %), CuI (1.0 equiv), base (2.0 equiv), 3 (0.036 mmol), and
b
c
aryl iodide (0.043 mmol) in toluene (0.5 mL) under nitrogen. Yields refer to isolated yields of diastereomeric mixtures after chromatography. The
diastereoselectivity was determined by high-performance liquid chromatography (OD-H column).
a
Table 5. Effect of Reaction Temperature on dr
Scheme 3. Cross-Coupling Reaction of Diphenylsilanol
b
c
entry
normal heating
time (h)
yield (%)
dr
1
2
3
r.t.
60
48
48
40
33
92
85
58:42
60:40
55:45
conditions at 100 °C were unsuccessful, resulting in a poor
yield of coupling product.
100
a
The isopropoxy analogue of silanol 3aa proved not to be a
competent coupling partner; treatment of this compound under
the conditions used for Ag2O-promoted coupling reactions
resulted in only unreacted starting material.
We also attempted to use Ag2O in combination with a
catalytic amount of Bu4NF·THF (0.1 equiv) to further improve
the reaction efficiency. Under these conditions, higher reactivity
than in reactions employing only Ag2O has been observed.25 In
the present case these conditions resulted in the formation of
products 5, demonstrating that protiodesilylation is preferred
Reaction conditions: Pd2(dba)3·CHCl3 (5 mol %), CuI (1.0 equiv),
NaOt-Bu (2.0 equiv), 3aa (0.036 mmol), and 4-iodoanisole (0.043
mmol) in toluene (0.5 mL) under nitrogen. Yields refer to isolated
yields of diastereomeric mixtures after chromatography. The
diastereoselectivity was determined by high-performance liquid
chromatography (OD-H column).
b
c
silanols.25 Attempts to decrease the reaction time by perform-
ing the reaction of 3aa with 4-iodoanisole under microwave
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a
Table 6. Cross Couplings of 3f−3h with Aryl Iodides Using Base as Activator
a
Unless stated otherwise, the reactions were carried out using Pd2(dba)3·CHCl3 (5 mol %), CuI (1.0 equiv), NaH (2.0 equiv), 3 (0.036 mmol), and
b
c
aryl iodide (0.043 mmol) in toluene (0.5 mL) under nitrogen. Yields refer to isolated yields of diastereomeric mixtures after chromatography. The
diastereoselectivity was determined by H NMR analysis. CuCl was used as additive instead of CuI.
d
1
Origin of Site Selectivity. Denmark has demonstrated that
Table 7. Cross-Coupling Reaction of 3aa with 4-
Bromoanisole
a
in the coupling of allylsilanols, the nature of the catalyst has a
dramatic influence on the α/γ ratio of the product.7 To
elucidate whether the type of product formed (1,2- or 1,3-
diene) was affected not only by the activator but also by the
choice of catalyst, Ag2O-promoted coupling of 3aa with 4-
methoxyiodobenzene was performed in the presence of
Pd2(dba)3·CHCl3 (2.5 mol %) in place of Pd(PPh3)4. Also
under these conditions only 1,3-diene was obtained, albeit in
lower yield (40% after 36 h at 60 °C as compared to 63% in the
presence of Pd(PPh3)4. We also employed Pd(PPh3)4 (5 mol
%) in combination with NaOt-Bu for the coupling of 3aa with
4-methoxyiodobenzene. This led to exclusive formation of
allene 4aa, although in merely 52% yield (as compared to 90%
using Pd2 (dba)3 ·CHCl3 ). As described above,
Pd2(dba)3·CHCl3 in combination with base and different
ligands also led exclusively to 1,2-dienes. These experiments
clearly demonstrate that the site selectivity is a function of the
activator.
b
entry heating source temperature (°C) time (h) isolated yield (%)
1
2
oil bath
MW
60
48
3
9
100
26
a
Unless stated otherwise, the reactions were carried out using
Pd2(dba)3·CHCl3 (5 mol %), CuI (1.0 equiv), NaOt-Bu (2.0 equiv),
3aa (0.036 mmol), and 4-bromoanisole (0.043 mmol) in toluene (0.5
b
mL) under nitrogen. Yields refer to isolated yields after
chromatography.
Scheme 4. Palladium-Catalyzed Cross Couplings Using
Fluoride as Activator
Mechanism and Stereochemistry. The contrasting
reactivity of 1,3-dienyl-2-silanols 3 in the presence of different
activating agents may be explained by different intermediates/
transition states for the reactions. Denmark has demonstrated
that, in the presence of base, silanol-based cross couplings
proceed via formation of a silanolate, which reacts with Pd(II)
to yield a complex with a Si−O−Pd linkage prior to
transmetalation.26
In the initially planar palladium diene complex (part A of
Scheme 5), the metal can coordinate to any of the enantiotopic
faces of the olefin. Formation of the allene requires rotation
around the C2−C3 single bond. The mode of coordination
determines the sense of rotation and, as a consequence, the
configuration of both newly formed stereogenic elements (axis
even in the presence of only minor amounts of water (Scheme
4).
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a
Table 8. Cross Couplings of 3 with Aryl Iodides Using Ag2O as Activator
a
Unless stated otherwise, the reactions were carried out using Pd(PPh3)4 (5 mol %), Ag2O (1.0 equiv), 3 (0.036 mmol), and aryl iodide (0.043
b
c
mmol, 1.2 equiv) in THF (0.5 mL) at 60 °C under nitrogen. Yields refer to isolated yields after chromatography. Cis/trans isomer ratios were
determined by H NMR spectroscopy. Reaction was carried out at 70 °C for 48 h. No reaction.
d
e
1
stereospecific palladium-catalyzed retro-propargylation of syn-
Scheme 5. Expected Stereochemistry of Base-Promoted
Coupling
and anti-propargyl alcohols 7a and 7b, respectively (Scheme
7).27 The two alcohols were prepared in a mixture and
1
separated by column chromatography. H NMR spectroscopy
(1H−1H coupling constants and nuclear Overhauser enhance-
ment spectroscopy (NOESY)) allowed unambiguous assign-
ment of their stereochemistry, which in turn permitted the
Scheme 7. Palladium-Catalyzed Retro-Propargylation27
and center). Thus, whereas 3aa is expected to lead to the R*,R*
diastereomer (Scheme 5), the E isomer 3b should lead to the
R*,S* product.
According to these assumptions, the product obtained from
silanol 3g should have syn stereochemistry (Scheme 6). To
verify this assumption, the two diastereomers were prepared
independently employing a published procedure involving
Scheme 6. Stereochemistry for Fomation of 4gb from 3g
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Fluoride-Activated Cross Coupling. To a solution of silanol 3aa
(9.8 mg, 0.036 mmol) in 0.5 mL of THF was added Pd(dba)2 (1.0 mg,
5 mol %), 4-iodoanisole (10.0 mg, 0.043 mmol, 1.2 equiv), and
Bu4NF·THF (0.072 mmol, 2.0 equiv). The resulting solution was
stirred at 25 °C for 20 h. After the completed reaction, the solvent was
removed, and the residue was purified by column chromatography
stereochemistry of the products 8a and 8b to be determined. In
line with our hypothesis, the syn-allene 8a was identical to the
product obtained by the silanol coupling (4gb).
The observation of mixtures of diastereomers may be the
result of isomerization around one of the olefinic bonds or,
alternatively, of facial exchange of palladium.
The mechanism of reactions promoted by Ag2O are less well-
known. Hiyama suggested a transition state with a Si−O−Ag
bond (Scheme 8).24 Alternatively, the role of silver may be to
1
(hexane/EtOAc = 80:1) to yield 5aa as a colorless liquid (97%). H
NMR (400 Hz, CDCl3): δ 7.42 (d, J = 6.4 Hz, 2H, Ph-H), 7.33 (t, J =
6.4 Hz, 2H, Ph-H), 7.24 (t, J = 6.4 Hz, 1H, Ph-H), 6.59 (d, J = 9.2 Hz,
1H, Ph−CH-), 6.39 (dt, J = 0.4, 9.2 Hz, 1H, −CHCHCH3), 5.63
(dq, J = 5.6, 9.2 Hz, 1H, −CHCHCH3), 2.63 (t, J = 6.4 Hz, 2H,
−CH2CH2CH2CH3), 1.83 (d, J = 5.6 Hz, 3H, −CHCHCH3),
1.30−1.42 (m, 4H, −CH2CH2CH3), 0.88 (t, J = 5.6 Hz, 3H,
−CH2CH3). 13C NMR (125 Hz, CDCl3): δ 143.52, 141.80, 128.62,
127.33, 127.21, 126.66, 126.13, 122.64, 31.67, 29.95, 23.09, 14.28,
13.76.
Scheme 8. Possible Routes for Formation of α- and γ-
Coupled Products
Ag2O-Activated Cross Coupling. Silanol 3ad (10.5 mg, 0.036
mmol) and tetrakis(triphenylphosphine)palladium(0) (2.0 mg, 5 mol
%) were added to 4-methoxyiodobenzene (10 mg, 0.043 mmol, 1.2
equiv) and silver(I) oxide (8.2 mg, 1.0 equiv) in 0.5 mL of THF. The
resulting suspension was stirred at 60 °C for 36 h and then filtered and
washed with CH2Cl2. After removal of the solvents, the residue was
purified by column chromatography (hexane/CH2Cl2 = 5:1) to yield
1
6ad as a colorless liquid (75%). H NMR (400 Hz, CDCl3): δ 6.95−
6.98 (m, 2H, Ph-H), 6.79−6.86 (m, 4H, Ph-H), 6.60 (d, J = 8.6 Hz,
2H, Ph-H), 6.32 (d, J = 11.2 Hz, 1H, −CH=CHCH3), 5.66 (dq, J =
7.0, 8.6 Hz, 1H, −CHCHCH3), 3.72 (s, 3H, -OCH3), 2.53 (t, J =
7.0 Hz, 2H, −CH2CH2CH2CH3), 1.39 (d, J = 7.0 Hz, 3H, −CH
CHCH3), 1.28−1.30 (m, 4H, −CH2CH2CH3), 0.86 (t, J = 7.0 Hz, 3H,
−CH2CH3). 13C NMR (125 Hz, CDCl3): δ 156.01, 137.66, 132.94,
132.66, 129.78, 129.60, 129.02, 126.12, 113.17, 112.96, 111.48, 53.55,
33.77, 30.10, 28.38, 21.34, 13.40, 12.49. IR (film): ν 3017, 2966, 2940,
2864, 2938, 1601, 1519, 1460, 1298, 1256, 1181, 1045, 830 cm−1.
help to ionize the Pd−I bond, thereby increasing the reactivity
of the palladium complex.28 The suggestion that different
palladium complexes are involved in the two types of reactions
is supported by the observation that a silyloxyplatinum complex
is not an intermediate in the analogous platinum-catalyzed
cross coupling of a silanol with an aryl iodide promoted by
Ag2O.29
ASSOCIATED CONTENT
CONCLUSION
■
■
S
* Supporting Information
In summary, we have demonstrated that silaborations of 1,3-
enynes provide adducts that can serve as 1,2- as well as 1,4-
dianion equivalents. The type of product obtained from
sequential Suzuki−Miyaura and Hiyama−Denmark cross
-coupling reactions can be controlled by the choice of activator
used in the last step. As a result, highly selective overall
monofunctionalization, 1,2-, or 1,4-difunctionalization of the
1,3-enyne to give tri- or tetrasubstituted 1,3-dienes or 1,2-
dienes, is observed. The reactions are examples of chemical
control of the chemo-, regio-, or diastereoselectivity from
identical starting materials, which is an attractive but
challenging concept to implement.
Experimental procedures, analytical data, and H NMR, 13C
1
NMR, and IR spectra for all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
kimo@kth.se
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
EXPERIMENTAL SECTION
We thank Dr. Zoltan Szabo for recording the NOESY spectra
and Professor Paul Helquist, University of Notre Dame, for
fruitful discussions. Financial support from the Carl Trygger
Foundation for Scientific Research and Swedish Research
Council is gratefully acknowledged.
■
Typical Procedures for Base-, Fluoride-, and Ag2O-Activated
Cross Coupling of 1,3-Dienyl-2-silanols. Base-Activated Cross
Coupling. To a solution of silanol 3g (11.3 mg, 0.036 mmol) in 0.5
mL of toluene was added NaH (1.7 mg, 0.072 mmol, 2 equiv). After
stirring for 10 min at room temperature, iodobenzene (4.8 μL, 0.043
mmol, 1.2 equiv), CuI (6.8 mg, 1.0 equiv), and Pd2(dba)3·CHCl3 (1.9
mg, 5 mol %) were sequentially added. The resulting brown solution
was stirred under microwave heating at 100 °C for 20 min. After
removal of the solvents, the residue was purified by column
chromatography (hexane) to give 4gb as a colorless liquid (96%).
1H NMR (400 Hz, CDCl3): δ 7.28−7.35 (m, 4H, Ph-H), 7.09−7.20
(m, 6H, Ph-H), 3.33 (dd, J = 3.2, 9.0 Hz, 1H, Cy-H), 2.50 (dt, J = 3.2,
10.0 Hz, 1H, Cy-H), 2.26 (td, J = 3.2, 10.0 Hz, 1H, Cy-H), 2.06−2.14
(m, 3H), 1.92−1.99 (m, 3H, Cy-H), 1.59−1.69 (m, 2H, Cy-H), 1.08−
1.20 (m, 4H, −CH2CH2CH3), 0.83 (t, J = 5.6 Hz, 3H, −CH2CH3).
13C NMR (125 Hz, CDCl3): δ 199.82, 144.16, 138.50, 128.43, 128.38,
128.05, 126.35, 126.19, 126.05, 110.57, 106.15, 48.49, 34.74, 32.66,
30.45, 30.12, 28.33, 26.64, 22.68, 14.39. IR (film): v 3088, 3063, 3024,
2938, 2854, 1953, 1604, 1496, 1453, 1246, 1034, 756 cm−1.
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