Palladium-Catalyzed Three-Component Reaction of Dihydrosilanes and Vinyl Iodides in the Presence of Alcohols: Rapid Assembly of Silyl Ethers of Tertiary Silanes

Article abstract of DOI:10.1002/chem.201805595

A one-pot reaction that directly converts dihydrosilanes into silyl ethers of tertiary silanes is reported. Under palladium catalysis, one Si?H bond of the dihydrosilane formally engages in C(sp³)?Si bond formation with a vinyl iodide while the other Si?H bond is transformed into a silyl iodide that undergoes facile alcoholysis with an alcohol. The C?C double bond is reduced in that process. This three-component reaction provides in a single synthetic operation an access to silyl ethers of functionalized and hindered alcohols. Several of those would otherwise be difficult to make but the intermediacy of a highly reactive silyl iodide even allows for tert-butanol to react at room temperature.

Full text of DOI:10.1002/chem.201805595

A Journal of
Accepted Article
Title: Palladium-Catalyzed Three-Component Reaction of
Dihydrosilanes and Vinyl Iodides in the Presence of Alcohols:
Rapid Assembly of Silyl Ethers of Tertiary Silanes
Authors: Weiming Yuan, Patrizio Orecchia, and Martin Oestreich
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To be cited as: Chem. Eur. J. 10.1002/chem.201805595
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10.1002/chem.201805595
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COMMUNICATION
Palladium-Catalyzed Three-Component Reaction of
Dihydrosilanes and Vinyl Iodides in the Presence of Alcohols:
Rapid Assembly of Silyl Ethers of Tertiary Silanes
Weiming Yuan, Patrizio Orecchia, and Martin Oestreich*[a]
Abstract: A one-pot reaction that directly converts dihydrosilanes
into silyl ethers of tertiary silanes is reported. Under palladium
catalysis, one Si‒H bond of the dihydrosilane formally engages in
C(sp3)‒Si bond formation with a vinyl iodide while the other Si‒H
bond is transformed into a silyl iodide that undergoes facile
alcoholysis with an alcohol. The C‒C double bond is reduced in that
process. This three-component reaction provides in
a single
synthetic operation an access to silyl ethers of functionalized and
hindered alcohols. Several of those would otherwise be difficult to
make but the intermediacy of a highly silyl iodide even allows for tert-
butanol to react at room temperature.
The transition metal-catalyzed cross-coupling of hydrosilanes
and C(sp2)‒X bonds with X being mainly iodide is a useful
method for the formation C(sp2)‒Si bonds.[1] Unlike the well-
established silylation of aryl halides,[2–4] related couplings of vinyl
halides have been far less investigated.[3d,5–6] A palladium-
catalyzed silylation of vinyl iodides was published by Masuda
and co-workers almost two decades ago,[5] followed by a
rhodium-catalyzed variant from Yamanoi and Nishihara.[3d] The
scope is relatively narrow and currently limited to
monohydrosilanes.
Scheme 1. Palladium-catalyzed cross-coupling of aryl and vinyl Iodides with a
dihydrosilane.
We used (E)-1-iodooct-1-ene (1a) and dihydrosilane 2a for the
initial optimization of the reaction conditions (Table 1). Applying
the optimal setup previously found for the arylation of 2a,[7] we
did observe the coupling product 4aa in 71% yield (entry 1).
Subsequent screening of other reaction parameters (entries
2‒6) showed that the result was best with Cy2NH as base in
CH2Cl2 (entry 4); the amine base was crucial, and K3PO4
completely suppressed the reaction (entry 6). Control
experiments verified that both catalyst and base are required for
this transformation (not shown). We were then surprised to find
that the addition of 3.0 equiv of MeOH (3a) had a dramatic effect
on the reaction outcome (entry 7); instead of vinyl-substituted
We recently reported a monoselective Yamanoi-type cross-
coupling of
a monosilane surrogate decorated with two
cyclohexa-2,5-dien-1-yl substituents and a broad range of aryl
iodides (Scheme 1, top).[7] By this, we have been able to access
aryl-substituted di(cyclohexa-2,5-dien-1-yl)silanes as central
building blocks for our custom synthesis of hydrosilanes. One of
the obvious next steps was the development of a related
vinylation to further expand the scope of that hydrosilane
synthesis (Scheme 1, bottom). However, while that cross-
coupling did indeed work, the reaction could be steered toward a
totally different outcome in the presence of alcohols or water.
4aa,
a new product characterized as 5aaa was formed
exclusively. The double bond had disappeared and the alcohol
was incorporated in form of a silyl ether. The same result was
obtained with other palladium (pre)catalysts (entries 8‒10), and
the yield was highest with (Ph3P)2PdCl2 (entry 10). A lower
alcohol loading of 2.0 equiv had little effect (entry 11) but the
yield decreased with equimolar amounts (entry 12); excess
alcohol was not detrimental (entry 13).
The net result of this three-component reaction of
a
dihydrosilane, a vinyl iodide, and an alcohol is a silyl ether of a
tertiary silane. We demonstrate the broad utility of this new
method in this Communication.
Table 1. Optimization of both the conventional vinylation and the three-
component reaction.[a]
[a]
Dr. W. Yuan, P. Orecchia, Prof. Dr. M. Oestreich
Institut für Chemie, Technische Universität Berlin
Strasse des 17. Juni 115, 10623 Berlin (Germany)
E-mail: martin.oestreich@tu-berlin.de
Homepage: http://www.organometallics.tu-berlin.de
Supporting information for this article is given via a link at the end of
the document.
Entry
Palladium
Base
MeOH
Solvent
Yield [%][b]
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10.1002/chem.201805595
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exclusion of potential intermediates
(Ph3P)2PdCl2 (5.0 mol%)
source
(equiv)
iPr2NH (3.0 equiv)
1
(tBu3P)2Pd
(tBu3P)2Pd
(tBu3P)2Pd
(tBu3P)2Pd
(tBu3P)2Pd
(tBu3P)2Pd
(tBu3P)2Pd
(Ph3P)4Pd
Pd(OAc)2
iPr2NH
iPr2NH
iPr2NH
Cy2NH
Et3N
—
—
—
—
—
—
3
benzene
CH2Cl2
1,2-Cl2C6H4
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
71 (4aa)
73 (4aa)
62 (4aa)
80 (4aa)
64 (4aa)
0 (4aa)
+
MeOH
CH2Cl2
RT for 16 h
Si
Si
2
nHex
nHex
H
MeO
3
4aa
3a
5aaa: not formed
(3.0 equiv)
4
(Ph3P)2PdCl2 (5.0 mol%)
iPr2NH (3.0 equiv)
5
+
MeOH
6
K3PO4
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
CH2Cl2
RT for 16 h
Si
Si
nHex
nHex
7
65 (5aaa)
85 (5aaa)
25 (5aaa)
93 (5aaa)
89 (5aaa)
H
MeO
6aa
3a
5aaa: not formed
8
3
(3.0 equiv)
9
3
deuterium-labeling experiments
10
11
(Ph3P)2PdCl2
(Ph3P)2PdCl2
3
(Ph3P)2PdCl2 (5.0 mol%)
iPr2NH (3.0 equiv)
Ph
Si
2
I
+
Ph SiH +
D3COD
2
2
Ph
OCD3
nHex
nHex
CH2Cl2
RT for 16 h
12
13
(Ph3P)2PdCl2
(Ph3P)2PdCl2
iPr2NH
iPr2NH
1
5
CH2Cl2
CH2Cl2
60 (5aaa)
94 (5aaa)
1a
2b
3a-d4
(3.0 equiv)
5aba-d3: 81%
(Ph3P)2PdCl2 (5.0 mol%)
iPr2NH (3.0 equiv)
D
Ph
Si
[a] All reactions were performed on a 0.1 mmol scale. [b] NMR yield with
CH2Br2 as internal standard.
I
+Ph2SiD2 +
EtOH
Ph
OEt
nHex
nHex
CH2Cl2
RT for 16 h
D
We found the unexpected reaction outcome more interesting
than the initially planned hydrosilane vinylation. To gain insight
into the mechanism of the formation of silyl ether 5aaa, we
performed a number of control experiments (Scheme 2). The
conventional cross-coupling product 4aa did not convert into
5aaa under the optimized setup with the alcohol (Scheme 2, top).
Moreover, independently prepared, hypothetical intermediate
6aa did not undergo dehydrogenative Si‒O coupling with MeOH
(3a) with this catalytic system (top). By this, vinylsilane 4aa and
alkylsilane 6aa were excluded as potential intermediates. To
further substantiate these results, both reactions were repeated
in the presence of 1.0 equiv of (E)-1-iodooct-1-ene (1a) but silyl
ether 5aaa was still not obtained (not shown). Additional
deuterium-labeling experiments using dihydrosilane 2b provided
useful evidence for the origin of 5aba and 5abb, respectively
(Scheme 2, bottom). When using CD3OD (3a-d4), no deuterium
incorporation into the alkyl chain of 5aba-d3 was seen. In turn,
selective deuteration α and β to the silicon atom, i.e., the
position of the former alkene unit, was found in 5abb-d2 with
Ph2SiD2 (2b-d2).
1a
2b-d2
3b
5abb-d2: 84%
(3.0 equiv)
Scheme 2. Control experiments for understanding the mechanism.
On the basis of the above experiments and according to the
literature precedence,[8] we suggest the following order of bond-
forming events (Scheme 3). Particularly for the related arylation
of hydrosilanes, it is documented that it competes with
hydrodehalogenation.[9] Yamanoi had introduced bulky
(tBu3P)2Pd as a catalyst that would usually disfavor the
undesired defunctionalization pathway.[8a,8b] This experimental
finding was indeed explained by an in-depth quantum-chemical
investigation but three different catalytic cycles are needed to
rationalize the subtle effects of the phosphine ligand and the
amine base.[10] Our vinylation of dihydrosilanes is in agreement
with this (Scheme 3, top): C(sp2)‒Si bond formation is seen with
(tBu3P)2Pd and hydrodeiodination is found with (Ph3P)2PdCl2;
the fact that the alcohol additive steers the reaction toward
defunctionalization even with (tBu3P)2Pd shows how sensitive
these cross-couplings are toward modifications (cf. entry 7 in
Table 1). The α-olefin emerging from the hydrodeiodination was
detected by 1H NMR spectroscopy. This then undergoes a
palladium-catalyzed hydrosilylation[11–13] directly with the in-situ-
generated silyl iodide R2Si(H)I or with R2Si(H)OMe after
preceding alcoholysis[14] (Scheme 3, middle). Either way, this is
how deuterium is incorporated into the β position (cf. Scheme 2,
bottom). When the alcoholysis[14] is downstream, the silyl ether
arises from the newly formed alkyl-substituted silyl iodide. A
control experiment where the α-olefin 7a was brought to reaction
with Ph2Si(H)Cl (8b) and MeOH (3a) under the standard setup
essentially ruled out the alcoholysis‒hydrosilylation pathway
(gray); the alkene was fully recovered and the silyl chloride had
undergone partial alcoholysis (Scheme 3, bottom). Also, when
the alcohol was added at the end of the reaction, silyl ether
formation was seen within minutes, lending further support to the
hydrosilylation‒ alcoholysis pathway (Scheme 3, bottom).[15]
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10.1002/chem.201805595
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Scheme 4. Scope I: Variation of the dihydrosilane and the vinyl iodide. [a]
Reaction performed on a 1.0 mmol scale. [b] The reaction mainly stops at the
hydrodeiodination stage, and α-methylstyrene is formed in major quantities.
A variety of alcohols was also examined (Scheme 5). Alcohols
3b,d‒m irrespective of steric hindrance led to good isolated
yields for 5. Functional groups such as alkyl or vinyl bromides,
terminal and internal alkenes (even allylic alcohol), alkynes, and
a Boc-protected secondary amine were fully compatible with this
palladium catalysis. Phenol (3n) and naphthols 3o and 3p
furnished 5abn‒abp. Remarkably, H2O (3q) could be employed,
yielding silanol 5abq in 73% isolated yield (gray box).
Scheme 3. Investigation of the order of bond-forming events.
With a high-yielding protocol for the three-component reaction in
hands, we tested different dihydrosilanes 2a‒e and
representative vinyl iodides 1a‒e (Scheme 4). Aside from
di(cyclohexa-2,5-dien-1-yl)-substituted 2a, other dihydrosilanes
such as Ph2SiH2 (2b), α-Np(Ph)SiH2 (2c), Me(Ph)SiH2 (2d), and
Et2SiH2 (2e) were compatible, and the corresponding silyl ethers
5 were isolated in good yields throughout. Other vinyl iodides
were prepared and subjected to the reaction. Besides the
primary alkyl substituent (as in 1a), a secondary (as in 1b) and a
tertiary (as in 1c) were tolerated equally well. Isolated yields for
5 were consistently high. (E)-β-iodostyrene (1d) did also work
yet with somewhat diminished yield of 5dba. Even (E)-β-iodo-α-
methylstyrene (1e) participated but the intermediate α-
methylstyrene did not fully convert in the hydrosilylation; silyl
ether 5eba was nevertheless isolated in 40% yield. This could
not be improved by increasing the reaction temperature to 45 °C
and 80 °C, respectively (sealed tube). A 1,2-disubstituted vinyl
iodide such as (E)-1-trimethylsilyl-2-iodoprop-1-ene afforded
hydrodeiodination exclusively; (E)-1-trimethylsilylprop-1-ene was
detected in 63% NMR yield (not shown). At a 1.0 mmol scale,
5aba was isolated with similarly high yield (86% vs 83%).
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COMMUNICATION
(Ph3P)2PdCl2 (5.0 mol%)
iPr2NH (3.0 equiv)
ROH (3b,d–q) (3.0 equiv)
fellowship to P.O., 2016–2019). M.O. is indebted to the Einstein
Foundation (Berlin) for an endowed professorship.
Ph
Si
Ph
Si
I
+
nHex
Ph
Ph
CH2Cl2
RT for 16 h
H
nHex
nHex
H
2b
OR
Keywords: cross-coupling • hydrosilylation • multi-component
1a
5
reactions • palladium • silicon
aliphatic alcohols
Ph
Si
Ph
Ph
Ph
Si
[1]
[2]
a) M. Shimada, Y. Yamanoi, H. Nishihara, J. Synth. Org. Chem. Jpn.
2016, 74, 1098‒1107; b) Z. Xu, W.-S. Huang, J. Zhang, L.-W. Xu,
Synthesis 2015, 47, 3645–3668; c) Y Yamanoi, H. Nishihara, J. Synth.
Org. Chem. Jpn. 2009, 67, 778‒786.
O
Si
Ph
Ph
OR
nHex
nHex
O
Me
BocN
5abb (R = Et): 83%
5abd (R = iPr): 82%
5abe (R = tBu): 76%
Ph
5abf: 80%
For palladium-catalyzed silylation of aryl halides, see: a) M. Murata, K.
Suzuki, S. Watanabe, Y. Masuda, J. Org. Chem. 1997, 62, 8569–8571;
b) A. S. Manoso, P. DeShong, J. Org. Chem. 2001, 66, 7449–7455; c)
M. Murata, H. Ohara, R. Oiwa, S. Watanabe, Y. Masuda, Synthesis
2006, 1771–1774; d) M. Murata, K. Ota, H. Yamasaki, S. Watanabe, Y.
Masuda, Synlett 2007, 1387–1390; e) M. Iizuka, Y. Kondo, Eur. J. Org.
Chem. 2008, 1161–1163; f) A. Lesbani, H. Kondo, J. Sato, Y. Yamanoi,
H. Nishihara, Chem. Commun. 2010, 46, 7784–7786; g) Y. Kurihara, M.
Nishikawa, Y. Yamanoi, H. Nishihara, Chem. Commun. 2012, 48,
11564–11566; h) Y. Kurihara, Y. Yamanoi, H. Nishihara, Chem.
Commun. 2013, 49, 11275–11277.
5abg: 72%
Ph
Si
Ph
Si
Ph
Si
Ph
nHex
O
Ph
Ph
nHex
nHex
Me
O
O
Br
Ph
Ph
5abi: 70%
5abh: 85%
5abj: 75%
Ph
Si
Ph
Si
Ph
Si
Ph
Ph
nHex
nHex
Ph
nHex
O
O
O
[3]
For rhodium-catalyzed silylation of aryl halides, see: a) M. Murata, M.
Ishikura, M. Nagata, S. Watanabe, Y. Masuda, Org. Lett. 2002, 4,
1843–1845; b) M. Murata, H. Yamasaki, T. Ueta, M. Nagata, M.
Ishikura, S. Watanabe, Y. Masuda, Tetrahedron 2007, 63, 4087–4094;
c) Y. Yamanoi, H. Nishihara, Tetrahedron Lett. 2006, 47, 7157–7161; d)
Y. Yamanoi, H. Nishihara, J. Org. Chem. 2008, 73, 6671–6678.
For platinum-catalyzed silylation of aryl halides, see: A. Hamze, O.
Provot, M. Alami, J.-D. Brion, Org. Lett. 2006, 8, 931–934.
Ph
Ph
Br
5abk: 76%
5abl: 74%
5abm: 84%
phenol and naphthols
water
Ph
Si
[4]
[5]
[6]
Ph
Si
5abn (R = Ph): 83%
5abo (R = -Np): 76%
5abp (R = -Np): 62%
Ph
nHex
OH
5abq: 73%
Ph
OR
nHex
M. Murata, S. Watanabe, Y. Masuda, Tetrahedron Lett. 1999, 40,
9255–9257.
For palladium-catalyzed silylation of vinyl halides with disilane, see: Y.
Hatanaka, T. Hiyama, Tetrahedron Lett. 1987, 28, 4715–4718.
W. Yuan, P. Smirnov, M. Oestreich, Chem 2018, 4, 1443–1450.
a) Y. Yamanoi, J. Org. Chem. 2005, 70, 9607–9609; b) Y. Yamanoi, T.
Taira, J.-i. Sato, I. Nakamula, H. Nishihara, Org. Lett. 2007, 9, 4543–
4546; c) A. Lesbani, H. Kondo, Y. Yabusaki, M. Nakai, Y. Yamanoi, H.
Nishihara, Chem. Eur. J. 2010, 16, 13519–13527.
Scheme 5. Scope II: Variation of the alcohol and experiment with H2O.
[7]
[8]
In summary, we reported here a new one-pot synthesis of silyl
ethers[16] from vinyl iodides, dihydrosilanes, and alcohols. The
alcohol component governs the reaction outcome. The three-
component reaction occurs in the presence of the alcohol
independent of the palladium (pre)catalyst used. Without the
alcohol additive and with (tBu3P)2Pd as catalyst, the
conventional C(sp2)‒Si cross-coupling is observed. The new
method directly transforms a wide range of dihydrosilanes into
silyl ethers of tertiary silanes by C(sp3)‒Si and Si‒O bond
formation in a single synthetic operation. Even hindered alcohols,
tert-butanol as an extreme example, participate at room
temperature as a result of the intermediacy of a highly reactive
silyl iodide. This distinguishes the present reaction from the
more conventional yet rare[16] two-step approach, that is
transition-metal-catalyzed hydrosilylation of α-olefins with
R2Si(H)Cl followed by Lewis-base-catalyzed silyl ether formation
of the far less reactive tertiary silyl chlorides.[16,17]
[9]
Palladium-catalyzed hydrodehalogenation of organic halides with
hydrosilanes, see: R. Boukherroub, C. Chatgilialoglu, G. Manuel,
Organometallics 1996, 15, 1508–1510.
[10] For a DFT study on palladium-catalyzed silylation of aryl iodides with
hydrosilanes, see: Z. Xu, J.-Z. Xu, J. Zhang, Z.-J. Zheng, J. Cao, Y.-M.
Cui, L.-W. Xu, Chem. Asian J. 2017, 12, 1749–1757.
[11] For a recent monograph on hydrosilylation, see: Hydrosilylation: A
Comprehensive Review on Recent Advances (Ed.: B. Marciniec),
Springer, Berlin, Germany, 2009.
[12] For selected reviews of transition-metal-catalyzed hydrosilylation of
alkenes, see: a) D. Teoegel, J. Stohrer, Coord. Chem. Rev. 2011, 255,
1440–1459; b) Y. Nakajima, S. Shimada, RSC Adv. 2015, 5, 20603–
20616.
[13] For reviews of earth-abundant transition-metal-catalyzed hydrosilylation
of alkenes, see: a) J. Sun, L. Deng, ACS Catal. 2016, 6, 290–300; b) X.
Du, Z. Huang, ACS Catal. 2017, 7, 1227–1243.
[14] For the alcoholysis of silyl iodides, see: M. R. Detty, M. D. Seidler, J.
Org. Chem. 1981, 46, 1283–1292.
[15] We did consider the formation of silylene intermediates but NMR
spectroscopic analysis of stoichiometric experiments with no alcohol
addition showed no indication of this.
Acknowledgements
This research was supported by the Cluster of Excellence
[16] Alcoholysis of silyl chlorides is very sensitive toward the steric
hindrance of both the silyl chloride and the alcohol. Tertiary silyl
chlorides with more than one phenyl group are often even stable
against moisture. Known examples are largely limited to RMe2SiCl with
R = alkyl.
Unifying
Concepts
in
Catalysis
of
the
Deutsche
Forschungsgemeinschaft (EXC 314/2) and the Berlin Graduate
School of Natural Sciences and Engineering (predoctoral
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[17] a) P. G. M. Wuts, T. W. Greene, Greene’s Protective Groups in Organic
Synthesis, 4th ed., Wiley, New York, USA, 2007, pp. 165‒221; b) P. J.
Kocieńsky, Protecting Groups, 3rd ed., Thieme, Stuttgart, Germany,
2004, pp. 188‒230.
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Suggestion for the Entry for the Table of Contents
COMMUNICATION
W. Yuan, P. Orecchia, M. Oestreich*
Page No. – Page No.
Palladium-Catalyzed Three-
Component Reaction of
Dihydrosilanes and Vinyl Iodides in
the Presence of Alcohols: Rapid
Assembly of Silyl Ethers of Tertiary
Silanes
Consuming alcohol. A conventional Yamanoi-type C(sp2)‒Si cross-coupling turns
into a C(sp3)‒Si bond formation accompanied by formal alkene hydrogenation in
the presence of alcohols or water. By this, dihydrosilanes are directly converted into
silyl ethers of tertiary silanes. Even bulky alcohols participate in this reaction
because of the intermediacy of a highly reactive silyl iodide.
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