An Efficient Approach to Regio- and Stereodefined Fully-Substituted Alkenylsilanes by Pd-Catalyzed Allenic C(sp3)?H Oxidation

Article abstract of DOI:10.1002/chem.201902962

A highly efficient palladium-catalyzed functionalization of allenylsilanes to give regio- and stereodefined fully-substituted alkenylsilanes has been developed. This oxidative coupling reaction showed good functional group compatibility with exclusive regio- and stereoselectivity. The pending olefin on the silyl group was shown to be an indispensable element for the initial allenic C(sp³)?H bond cleavage, and performs as the directing group to control the overall selectivity. The addition of substoichiometric amounts of Et₃N was found to increase the reaction rate leading to a higher reaction yield. The reaction can be easily scaled up and applied for the late-stage functionalization of natural products and pharmaceutical compounds, including amino acids and steroid derivatives. The newly introduced functional groups include aryl, alkynyl, and boryl groups. The highly strained four-membered ring, silacyclobutene was obtained when B₂pin₂ was employed as the coupling partner. Mechanistic studies, including kinetic isotope effects, showed that the allenic C(sp³)?H bond cleavage is the rate-limiting step.

Full text of DOI:10.1002/chem.201902962

A Journal of
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Title: An Efficient Approach to Regio- and Stereodefined Fully-Substi-
tuted Alkenylsilanes via Pd-Catalyzed Allenic C(sp3)-H Oxidation
Authors: Jan-E. Bäckvall and Can Zhu
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10.1002/chem.201902962
Chemistry - A European Journal
RESEARCH ARTICLE
An Efficient Approach to Regio- and Stereodefined Fully-Substi-
tuted Alkenylsilanes via Pd-Catalyzed Allenic C(sp3)–H Oxidation
Can Zhu* and Jan-E. Bäckvall*
Abstract: A highly efficient palladium-catalyzed functionalization of
allenylsilanes to give regio- and stereodefined fully-substituted
alkenylsilanes has been developed. This oxidative coupling reaction
showed good functional group compatibility with exclusive regio- and
stereoselectivity. The pending olefin on the silyl group was shown to
be an indispensable element for the initial allenic C(sp3)–H bond
cleavage, and performs as the directing group to control the overall
selectivity. Substoichiometic amounts of Et3N was found to increase
the reaction rate leading to a higher yield of the reaction. The
reaction can be easily scaled up and applied for the late-stage
functionalization of natural products and pharmaceutical compounds,
including amino acids and steroid derivatives. The newly introduced
functional groups include aryl, alkynyl, and boryl groups. The highly
strained four-membered ring, silacyclobutene was obtained when
B2pin2 was employed as the coupling partner. Mechanistic studies,
including kinetic isotope effects, showed that the allenic C(sp3)–H
bond cleavage is the rate-limiting step.
Introduction
etrasubstituted olefins, a class of fundamentally important
compounds, are ubiquitous in various natural products, as
T
well as pharmacologically active compounds.[1-3] Their
biological properties are highly determined by the configuration
of the carbon-carbon double bond.[4,5] Functionalized
tetrasubstituted olefins, where one of the substituents is a
functional group, are considered as a class of useful and
fundamental building blocks for complex molecules in organic
synthesis (Scheme 1a).[6] In this field, alkenyl halides have
shown wide applications as electrophiles in coupling reactions,[7]
while alkenylmetal reagents, such as alkenylmagnesium and
alkenylzinc reagents are used as nucleophiles in carbon-carbon
bond forming reactions.[8] However, the use of these strong
nucleophiles is associated with problems concerning functional
group compatibility. For example, carbonyl compounds,
including aldehydes and ketones, are sensitive to alkenylmetal
reagents of magnesium and zinc.[9] Therefore, less nucleophilic
alkenylmetal reagents as those of boron[10] and silicon[11,12] are
Scheme 1. Proposal for the synthesis of regio- and stereopure fully-
substituted alkenylsilanes.
tion of alkenylboranes are known, methods for the synthesis of
the corresponding alkenylsilanes are less common.[10-12]
Organosilanes[11,12] have found widespread applications in,
for example, Hiyama coupling reactions,[13] Hosomi-Sakurai
reactions,[14] and Fleming-Tamao oxidations.[15] Vinylsilane
moieties are valuable linchpins in synthetic chemistry and typical
procedures for their preparation are based on the hydrosilylation
of alkynes,[16] or coupling reaction of alkenyl halides with silicon
(pro)nucleophiles (Scheme 1b).[17] In these transformations,
regio- and stereoselectivity can be controlled by the catalyst or
the substrate. However, these methods mostly lead to mono-
and di-substituted alkenylsilanes, in which one of the
substituents is a hydrogen atom. To the best of our knowledge,
regio- and stereoselective methods for the synthesis of fully-
substituted alkenylsilanes are rare.[18] Therefore, the
development of efficient methods for the synthesis of these
alkenylsilanes is highly desirable. We envisioned that, with a
suitable directing group (DG) on the silyl group of an
allenylsilane, the stereochemistry for a transition metal-catalyzed
coupling reaction with the allenylsilane could be nicely controlled
(Scheme 1c).[19] In this way stereodefined alkenylsilanes with a
tetrasubstituted double bond would be obtained.
highly attractive. Although
procedures for the prepara-
a
range of well-established
[*]
Dr. C. Zhu, Prof. Dr. J.-E. Bäckvall
Department of Organic Chemistry, Arrhenius Laboratory
Stockholm University, Stockholm, SE-10691, Sweden
E-mail: zhucaner@gmail.com
jeb@organ.su.se
Supporting information for this article is given via a link at the end of
the document.
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Our group has been involved in research concerning the
palladium-catalyzed oxidative carbocyclization/functionalization
of enallenes.[20] We recently found that the activation of the
allene to attack palladium to form the dienyl-Pd key intermediate
Int-B, requires additional coordination of the pending olefin as
shown in Int-A (Scheme 2).[20e] A π‐bond-containing group, such
as an olefin or acetylene group triggers the allene attack on
Pd(II)[20e,g] and these unsaturated groups have been employed
as directing groups in many C–H functionalization reactions.[21]
Based on our previous studies for olefin activation,[21b] an olefin
group was introduced on the silyl group, and evaluated as a
directing group to control the stereoselectivity.
one stereoisomer where the silyl and phenyl group are cis to one
another. The stereochemistry of 3aa was established by NOE
studies.[23]
Scheme 3. Preliminary results.
Inspired by these exciting results, we set out to optimize the
reaction conditions. Interestingly, a decrease of the reaction
temperature to room temperature increased the yield of 3aa to
50% (Table 1, entry 2). The solvent effect was then investigated
(Table 1, entries 3-6). Toluene, DCE, and MeCN as solvent
gave poor yield (5-15%) whereas dioxane afforded 3aa in 41%
yield with 32% recovery of 1a. By prolonging the reaction time in
dioxane to 16 h, silane 3aa was obtained in 60% yield (Table 1,
entry 7). Moreover, we investigated the effect of additives in this
oxidative reaction. The desired phenyl coupling was found to be
favored under basic reaction conditions rather than acidic
conditions, as shown by the outcome of the reactions with
Scheme 2. Olefin effect for the allene attack.
Results and Discussion
Our initial attempts began with the coupling reaction of
allenyl-vinylsilane 1a[22] with phenylboronic acid 2a under the
catalysis of Pd(OAc)2 (5 mol%) (Scheme 3).[20e] To our delight,
the reaction in THF with BQ (BQ = p-benzoquinone, 1.1 equiv)
as the oxidant afforded tetrasubstituted olefin 3aa in 26% yield.
It is noteworthy that the product obtained (3aa) is exclusively
additional Et3N or HOAc (Table 1, entries
8 and 9).
Table 1. Optimization of the Reaction Conditions[a]
Entry
Solvent
PdII [x (mol%)]
Additive (mol%)
Temp./oC
Time/h
Yield of 3aa [%][b]
Recovery of 1a
[%][b]
1
2
3
4
5
6
7
8
9
10
11
12
13
14[c]
15[d]
16[d]
17[d]
18[d]
19[d]
THF
THF
toluene
DCE
MeCN
Pd(OAc)2 [5]
Pd(OAc)2 [5]
Pd(OAc)2 [5]
Pd(OAc)2 [5]
Pd(OAc)2 [5]
Pd(OAc)2 [5]
Pd(OAc)2 [5]
Pd(OAc)2 [5]
Pd(OAc)2 [5]
Pd(TFA)2 [5]
Pd(OPiv)2 [5]
Pd(OAc)2 [5]
Pd(OAc)2 [5]
Pd(OAc)2 [5]
Pd(OAc)2 [5]
Pd(OAc)2 [1]
Pd(OAc)2 [0.5]
Pd(OAc)2 [0.1]
-
-
-
-
-
-
-
-
50
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
4
4
4
4
4
4
16
6
6
6
26
50
15
6
-
-
42
-
58
32
-
-
34
-
56
-
-
-
-
-
-
47
99
5
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
41
60
69
25
35
29
80
76
62
93
95
97
48
-
Et3N (20)
HOAc (20)
Et3N (20)
Et3N (20)
Et3N (50)
Et3N (100)
Et3N (50)
Et3N (50)
Et3N (50)
Et3N (50)
Et3N (50)
Et3N (50)
6
6
4
6
6
12
12
12
12
[a] Conditions: the reaction was conducted in the indicated solvent (1 mL) with allenylsilane (1a, 0.2 mmol), PhB(OH)2 (2a, 1.3 equiv), and BQ (1.1 equiv) in
the presence of Pd(OAc)2 (5 mol %). [b] The yield was determined by 1H NMR analysis using anisole as the internal standard. [c] C = 0.05 M. [d] PhB(OH)2 (1.5
equiv)
was
used.
Pd(TFA)2
=
palladium
trifluoroacetate.
Pd(OPiv)2
=
palladium
pivalate.
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Furthermore, screening of the palladium catalyst showed that
Pd(OAc)2 was the best catalyst in this reaction (Table 1, entries
8, 10 and 11). An increase of the amount of the Et3N additive (50
mol%) increased the yield of product 3aa up to 80% (Table 1,
entries12 and 13). The reaction yield went down to 62% on
decreasing the reaction concentration (Table 1, entry 14). To our
delight, 93% yield of the corresponding silane 3aa was obtained
when the amount of PhB(OH)2 was increased to 1.5 equiv. It is
noteworthy that the use of 1 mol% of Pd(OAc)2 afforded a
slightly higher yield (95%) of 3aa (Table 1, entry 16).
Encouraged by these results, the catalyst loading was
decreased even further to 0.5 mol%, which afforded 3aa in 97%
yield (Table 1, entry 17). However, the use of 0.1 mol% of
Pd(OAc)2 gave only 48% yield of 3aa together with 47% of
recovered starting material 1a (Table 1, entry 18). Finally, the
reaction was not working at all in the absence of palladium
catalyst as shown in a control experiment (Table 1, entry 19).
With the optimal reaction conditions in hand, we turned to
studying the substrate scope of this oxidative arylation (Scheme
5). First, arylboronic acids with a range of substituents at the
meta-position of the benzene ring were examined: the
analogues with electron-donating substituents, such as Me and
MeO, reacted smoothly to give the products 3ab and 3ac in
excellent yields. The substrates with electron-withdrawing
substituents in the meta-position, including NO2 and F, worked
equally well and the corresponding coupling products 3ad and
3ae were obtained in high yields. Substituents in the para-
position were also investigated: The free p-hydroxyl group was
nicely tolerated under the reaction conditions, and alkenylsilane
3af was obtained in 89% yield from 1a. Other functional groups
in the para-position of the benzene ring of the arylboronic acids,
t
including Me, MeO, F, NO2, acetyl, Bu, vinyl, and CHO were
also tolerated leading to the corresponding products 3ag-3an in
excellent yields. Silane 3ao was smoothly generated via the
To further confirm the effect of the pending olefin group on Si, oxidative coupling reaction of 1a with 2-naphthylboronic acid.
we next carried out comparative experiments. The vinyl group
on Si in 1a was replaced by a phenyl (1a-B) or methyl (1a-C)
group (Scheme 4). The reactions of 1a-B and 1a-C under the
standard reaction conditions (cf. entry 17 in Table 1) failed to
give any detectable amounts (<1%) of the corresponding
products 3aa-B and 3aa-C, respectively. These results indicate
that the olefin group on Si is an indispensable assisting/directing
group for the allene oxidative arylation. Moreover, the reaction of
1a-D, where one of the methyl groups on Si in 1a was replaced
by a phenyl group gave the corresponding alkenylsilane 3aa-D
in 98% yield, and high stereoselectivity (>99% cis relationship
between Si and Ph). The stereochemistry was confirmed by
NOE studies.[23] These observations indicate that the
coordination of the vinyl group on Si during the reaction
accounts for the stereochemistry of the products. The vinyl
group on Si directs the phenyl group installed to the same side
as Si in the tetrasubstituted olefin formed.[21]
Furthermore, we studied different types of allenes.
Cycloalkylidene allenes could also be employed in the
coupling reaction, affording products 3b-f in 88-96% yields. To
exhibit the broad scope of allenes in this transformation, we
chose other functional group-containing allenes: allenylsilane
1g, bearing a phenyl group, also showed excellent reactivity as
o
shown by the formation of 3g in 86% yield at 40 C. It is worth
noting that the reaction of allenylsilane 1h, having a free OH
group, failed to give the corresponding product 3h. In the latter
case, a dihydrofuran product was obtained in 94% yield instead,
proceeding via oxypalladation and β–H elimination.[24] However,
the employment of 1i and 1j, in which the hydroxyl group was
protected, successfully afforded alkenylsilanes 3i and 3j in 94%
and 96% yield, respectively. Finally, it is worth noting that
products with cis-selectivity of the silyl and aryl group were the
only isomers obtained under these reaction conditions.
To demonstrate the applicability of the methodology
developed herein, substrates with nitrogen-containing functional
groups were also employed, because they are widely found in
natural products and drug molecules (Scheme 5). The oxidative
arylation reaction of 1k, bearing an imide group, afforded 3k in
95% yield. Moreover, this stereospecific reaction could also be
applied to α-amino acid derivative 1l, affording the
corresponding product 3l in 91% yield. Lithocholic acid is known
as an important bile acid in the human body and can selectively
kill neuroblastoma cells without hurting normal neuronal cells.[25]
The employment of lithocholic acid derivative in this reaction led
to silane 3m in excellent yield (94%), showing the potential of
the method in late-stage functionalization in biomolecular and
medicinal chemistry.
Scheme 4. Comparative experiments. [a] Isolated yield via filtration. [b] 1a-B
was recovered in 64% yield as determined by 1H NMR analysis. [c] 1a-C was
recovered in 91% yield as determined by 1H NMR analysis.
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Scheme 5. Substrate Scope. Reaction conditions: the reactions were conducted in dioxane (1 mL) with allenylsilane 1 (0.2 mmol), ArB(OH)2 2 (1.5 equiv), and
BQ (1.1 equiv) in the presence of Pd(OAc)2 (0.5 mol %) and Et3N (50 mol%) at room temperature for 12 h. Isolated yield after column chromatography or filtration.
[a] The reaction was run at 40 oC. [b] The reaction of 1h gave a dihydrofurane (12) via an intramolecular trans-1,2-oxypalladation.[24]
Finally, 1.5 gram-scale synthesis of alkenylsilane 3aa
without any chromatography purification was realized from
allenylsilane 1a, which is readily obtained from commercially
available compounds via a three-step synthesis (Scheme 6).
stereodefined dienyne 7a in 97% yield from reaction of 1a with
phenylacetylene. This cross-dehydrogenative coupling (CDC)[26]
is highly efficient and selective and 7a was the only
stereoisomer observed. The configuration of the C=C bond in 7a
was established by NOE studies.[23] The reaction of allenylsilane
1d with ethynyltrimethylsilane afforded the di-silane product 7b
in 93% yield. Moreover, an imide group was also nicely tolerated
in this alkynylation reaction, as shown by the reaction of
allenylsilane 1k with phenylacetylene to give 7c in 88% yield.
Given the fact that boron-containing functional groups can be
readily transformed into many other functional groups,[27] the
introduction of a boryl group using B2pin2 was explored. To our
surprise, Pd-catalyzed reaction of 1a with B2pin2 in THF afforded
silacyclobutene 8, bearing a highly strained four-membered
ring,[28] as the major product (71% yield), together with 16% yield
of alkenylboron compound 9. The insertion of the pending olefin
into the vinyl-Pd bond (cf. Int-B in Scheme 2) led to the
formation of silacyclobutene product 8, while alkenylboron
compound 9 was generated via the direct borylation of the vinyl-
Pd bond with B2pin2. A similar effect was previously observed in
the borylative Pd(II)-catalyzed oxidative carbocyclization of 1,4-
enallenes to give cyclobutenes.[29,30] It is noteworthy that the
reaction without Et3N gave only 16% yield of 8 together with 6%
yield of 9. Obviously, the formation of silacyclobutene product 8
Scheme 6. Gram-Scale Synthesis of 3aa. EE = 1-ethoxyethyl. PPTS =
pyridinium p-toluenesulfonate.
To show the diverse functionalization of allenylsilanes 1 in
the palladium-catalyzed oxidative reaction, their coupling with
terminal alkynes were next investigated under the standard
reaction conditions (Scheme 7). To our delight, a selective
alkynylation could be realized, as shown by the formation of
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is highly favored in the presence of substoichiometic amounts of
Et3N.
We next turned to carrying out mechanistic studies (Scheme
9). Control experiments in the oxidative phenylation reaction was
conducted under the catalysis of Pd(TFA)2, which has a more
cationic palladium compared to Pd(OAc)2. To our surprise, the
reaction of 1a afforded only 35% yield of the silane product 3aa
together with enyne product 11 in 33% yield. Instead of the
direct coupling with PhB(OH)2 to give 3aa, the Pd intermedaite
Int-C underwent
observations further support that Int-C is the key intermediate
for the overall transformation. Furthermore, crossover
a
cis-β-Si-elimination to afford.[34] These
a
experiment was set up using a mixture of 1j and d6-1a under the
standard reaction conditions, which afforded products of 3j and
d5-3aa in 99% and 85% yield, respectively. No intermolecular H-
D exchange was observed during the reaction, which requires
that the allenic C–H bond cleavage is irreversible in this
oxidative reaction.
Scheme 7. Oxidative functionalization using terminal alkynes and B2pin2. [a]
Isolated yield after column chromatography. [b] 1a was recovered in 9% yield,
and yields of 8 and 9 were determined by 1H NMR analysis using anisole as
the internal standard.
Further transformations of alkenylsilane 3aa were next
investigated (Scheme 8). It is very convenient to remove the silyl
functional group by heating the reaction of 3aa with
o
trifluoroacetic acid at 95 C for 2 h. This reaction afforded the
Scheme 9. Mechanistic studies.
stereodefined tri-substituted olefin 10 in 93% yield. The
configuration of the C=C bond in 10 was confirmed by NOE
measurements.[23] It is known that introduction of deuterium into
active pharmaceutical compounds may enhance their
pharmacokinetic and pharmacodynamic properties, resulting in
better pharmacological activities.[31] Therefore, the development
of efficient methods for selective deuteration has recently
attracted much attention.[32] When 2.5 equiv of deuterated
trifluoroacetic acid was added to the reaction, the stereospecific
deuteration led to tri-substituted olefin d-10 in 78% yield, with
66% d-incorporation. With the use of 5 equiv of deuterated
trifluoroacetic acid, the yield of d-10 was improved to 84%, with
82% d-incorporation. Finally, selective hydrogenation and
diiodination of the pending olefin gave vinysilanes 3aa’ and 3aa’’
in 91% and 92% yield, respectively. Vinyl silanes 3 (e.g. 3aa)
are also potential precursors for fully carbon tetrasubstituted
olefins through a Hiyama cross-coupling reaction.[13,33]
Next, the effect of Et3N in the reaction was investigated by
carrying out the comparative experiments with different
substoichiometic amounts of Et3N (10 mol% and 50 mol%
respectively), or without Et3N (Figure 1). The reaction in the
absence of Et3N was slow and had a long induction period
(approx. 25 min), while the reaction with 10 mol% of Et3N was
faster and gave only a short induction period (approx. 7 min).
From these results, we conclude that Et3N accelerates the
reaction rate resulting in a higher yield of the product. When the
amount of Et3N was increased to 50 mol%, the rate of the
reaction was further increased compared to that with 10 mol% of
Et3N. These results suggest that the rate-accelerating effect of
Et3N on the reaction is probably due to its activation of the
substrate, rather than acting as a ligand to palladium.
Scheme 8. Transformations of alkenylsilane 3aa. [a] 3aa was recovered in
14% yield.
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latter step is the rate-limiting step during the overall
transformation.20 The coupling reactions of Int-2 with arylboronic
acids or terminal alkynes give the corresponding products 3 and
7, respectively. The released Pd(0) is reoxidized to Pd(II) by BQ,
which closes the catalytic cycle. When B2pin2 was employed as
the coupling partner, the migratory insertion of the pending olefin
into the vinyl-Pd bond in intermediate Int-2 was favored and
afforded silacyclobutene Int-3. Subsequent borylation afforded
boron compound 8 as the major product. However, the direct
borylation reaction of Int-2 also occurred to generate
alkenylborane 9 as a minor product. Finally, a rare cis-β-Si-
elimination in Int-2 occured with the more cationic palladium
catalyst [Pd(TFA)2] to give enyne 11.
70
60
50 mol% Et3N
50
40
30
20
10
0
10 mol% Et3N
no Et3N
0
20
40
60
Time/min
Figure 1. Effect of Et3N.
To gain a deeper insight into the mechanism of this oxidative
coupling reaction, the deuterium kinetic isotope effects (KIE)
were studied.[35] An intermolecular competition experiment was
carried out using a 1:1 mixture of allenylsilane 1a and [D6]-1a at
room temperature for 15 min (eq. 1, Scheme 10). The product
ratio 3aa/[D5]-3aa (ca. 37% conv.) was found to be 5.3:1. From
this ratio, the competitive KIE was determined to be kH/kD
=
7.9.[36] Moreover, two parallel experiments with 1a and [D6]-1a
gave a KIE (kH/kD from initial rate) value of 4.9 (eqs. 2 and 3,
Scheme 10). These observed kinetic isotope effects indicate that
the allenic C–H bond cleavage occurs during the rate-limiting
step (RDS). The large competitive isotope effect in the allenic
C–H bond cleavage (kH/kD = 7.9) requires that this step is the
first irreversible step, which is consistent with the reaction
outcome in the crossover experiment in Scheme 9.
Scheme 11. Proposed reaction mechanism.
Conclusion
In conclusion, we have developed efficient palladium-catalyzed
oxidative functionalizations of allenylsilanes, which provide
regio- and stereodefined fully-substituted alkenylsilanes. The
reaction requires only 0.5 mol% Pd(OAc)2 and produces
exclusively one regio- and stereoisomer in high yields. The
pending olefin acts as
a directing group to control the
stereoselectivity as confirmed by control experiments.
Substoichiometic amounts of Et3N was found to increase the
reaction rate by activating the substrate leading to an enhanced
yield of the corresponding products. The observed kinetic
isotope effects, both in competitive and parallel experiments
show that the initial allenic C(sp3)–H bond cleavage is the rate-
limiting step. Moreover, the reaction is easily scalable and silane
3aa was prepared on a 1.5 gram-scale from the corresponding
allenylsilane without column chromatography purification. The
newly installed functional groups include aryl, alkynyl and boryl
groups. Interestingly, the highly strained four-membered ring,
silacyclobutene was generated as the major product when
B2pin2 was employed as the coupling partner. The reaction
developed have potential applications in the synthesis of natural
products and pharmacologically active substances. Finally,
further diverse transformations of the products and the
asymmetric synthesis of silacyclobutenes are under way in our
laboratory.
Scheme 10. Studies on kinetic isotope effects.
Based on the studies carried out im Scheme 9 and 10 a
possible mechanism for this oxidative reaction is proposed in
Scheme 11. The pending C=C bond considered as the directing
group, coordinates to the PdII center together with the allenic
C=C bond of the substrate affording the chelate Int-1.21 The
subsequent allene attack involves allenic C(sp3)-H bond
cleavage, and generates vinylpalladium intermediate Int-2. The Acknowledgements
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4392–4396; Angew. Chem. Int. Ed. 2017, 56, 4328–4332; c) J. Guo, X.-
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Ed. 2017, 56, 615–618; d) C. Wu, W. J. Teo, S. Ge, ACS Catal. 2018, 8,
5896–5900.
Financial support from the Swedish Research Council (2016-
03897), the Foundation Olle Engkvist Byggmästare, the Berzelii
Center EXSELENT, and the Knut and Alice Wallenberg
Foundation is gratefully acknowledged.
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Keywords: palladium • oxidation • tetrasubstituted olefins •
regio- and stereoselectivity • allenylsilane
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An Efficient Approach to Regio- and
Stereodefined Fully-Substi-tuted
Alkenylsilanes via Pd-Catalyzed
Allenic C(sp3)–H Oxidation
Palladium-catalyzed regio- and stereoselective synthesis of fully-substituted
alkenylsilanes from allenylsilanes has been developed under oxidative conditions.
This coupling reaction showed broad substrate scope and good functional group
compatibility. The pending olefin on the silyl group was an indispensable moiety for
the initial allenic C(sp3)–H bond cleavage, which is the rate-limiting step. In addition,
this olefin acts as the directing group to control the overall selectivity. With
substoichiometic amounts of Et3N, the reaction can be easily scaled up, and
applied in late-stage functionalizations. The newly introduced functional groups
include aryl, alkynyl, and boryl groups. The highly strained four-membered ring,
silacyclobutene was obtained in the reaction with B2pin2.
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