Regio- and stereoselective hydrosilylation of immobilized terminal alkynes

Article abstract of DOI:10.1016/j.tetlet.2008.08.043

Regio- and stereoselective hydrosilylation of terminal alkynes on solid support using diisopropyl hydrosilanes yielding β-(E)-vinyl silanes with excellent selectivity is reported. The hydrosilylation is catalyzed by Pt(DVDS)/P(ⁱBuNCH₂CH₂)₃N (DVDS = 1,3-divinyl-1,1,3,3-tetramethyl-disiloxane), in which the bulky proazaphosphatrane ligand plays a key role for the selectivity. The immobilized products are characterized with gel phase ¹³C NMR and ¹H high resolution magic angle spinning NMR.

Full text of DOI:10.1016/j.tetlet.2008.08.043

Tetrahedron Letters 49 (2008) 6220–6223
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Regio- and stereoselective hydrosilylation of immobilized terminal alkynes
*
Palle J. Pedersen, Jonas Henriksen, Charlotte H. Gotfredsen, Mads H. Clausen
Department of Chemistry, Technical University of Denmark, Building 201, DK-2800 Kgs. Lyngby, Denmark
a r t i c l e i n f o
a b s t r a c t
Article history:
Regio- and stereoselective hydrosilylation of terminal alkynes on solid support using diisopropyl hydro-
silanes yielding b-(E)-vinyl silanes with excellent selectivity is reported. The hydrosilylation is catalyzed
by Pt(DVDS)/P(iBuNCH2CH2)3N (DVDS = 1,3-divinyl-1,1,3,3-tetramethyl-disiloxane), in which the bulky
proazaphosphatrane ligand plays a key role for the selectivity. The immobilized products are character-
ized with gel phase 13C NMR and 1H high resolution magic angle spinning NMR.
Received 16 July 2008
Revised 5 August 2008
Accepted 11 August 2008
Available online 14 August 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Hydrosilylation
Polyethylene glycol resins
High resolution magic angle spinning NMR
Immobilization
Solid supported organic synthesis is dependent on efficient reac-
tions that are compatible with the supports and meets the special
demands of immobilized reactants. With this in mind we have
investigated the regio- and stereoselective hydrosilylation of
terminal alkynes yielding b-(E)-vinyl silanes. The hydrosilylation
reaction, discovered by Sommer et al. in 1947,1 can be characterized
as an addition of hydrosilanes to unsaturated carbon–carbon (or
carbon-heteroatom) bonds such as alkenes and alkynes. The
cat.
SiR'3
β-(E)
R
+
HSiR'3
R
H
+
+
R
R
SiR'3
SiR'3
β-(Z)
α
Scheme 1.
OMe
OMe
iBu
iBu
iBu
N
P
N
Si
H
N
4
4
No reaction
N
a
a
1
2
OMe
Si
H
Si
3
5
83%
Scheme 2. Reagents and conditions: (a) Pt(DVDS)/1 (1 mol %), THF, 23 h, 20 °C.
* Corresponding author. Tel.: +45 45252131; fax: +45 45933968.
E-mail address: mhc@kemi.dtu.dk (M. H. Clausen).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.043

P. J. Pedersen et al. / Tetrahedron Letters 49 (2008) 6220–6223
6221
Hydrosilylation of terminal alkynes could result in three iso-
meric vinyl silanes as illustrated in Scheme 1. Even though both
the Karstedt and the Speier catalysts favor the formation of the
Cl
7
OH
O
b-(E)-vinyl silane isomer, the a-vinyl silane is produced to a signif-
icant degree (10–30%),3 whereas b-(Z)-vinyl silanes usually do not
appear above the trace level when these catalysts are applied. Re-
cently, Denmark et al. and others3a–c demonstrated that addition of
8
a
6
Scheme 3. Reagents and conditions: (a) KOtBu, Bu4NI, THF, 40 h, 60 °C.
bulky phosphorus ligands improved the b-(E):a ratio significantly
and by applying the commercially available triisobutyl proaza-
phosphatrane ligand 14 Verkade and co-workers obtained the
b-(E) isomer with over 97% selectivity and in good yields.3b
reaction can be catalyzed by various metal complexes, with the plat-
inum compounds Pt(DVDS)2 (Karstedt’s catalyst)2a and H2PtCl6ꢀ
6H2O (Speier’s catalyst)2b as the most prominent and popular.
OMe
OMe
Si
Si
H
4
O
O
a
8
9
Scheme 4. Reagents and conditions: (a) Pt(DVDS)/1 (1 mol %), THF, 53 h, 60 °C.
Figure 1. 1H HR-MAS NMR (500 MHz, CDCl3) spectra of resins 6, 8 and 9, including proton assignment.

6222
P. J. Pedersen et al. / Tetrahedron Letters 49 (2008) 6220–6223
Table 1
sobutyl proazaphosphatrane ligand 1. We did not observe any
product formation in the experiment with styrene, whereas phenyl
acetylene was converted to the desired b-(E)-vinyl silane 5 in 83%
yield with better than 98% selectivity.9
One of the challenges of working with solid phase synthesis is
the analysis and characterization of the immobilized compounds.
High resolution magic angle spinning NMR (HR-MAS NMR)
has been shown to be a very powerful tool for structure elucida-
tion of polymer-bound molecules.10 1H HR-MAS NMR and gel
phase 13C NMR11 are very valuable and robust techniques in the
characterization of the immobilized molecules in the present
study.
In this Letter we used the polyethylene glycol (PEG) based solid
support VersaBeadsTM VO 2000 (6), which is a modified superper-
meable organic combinatorial chemistry (SPOCC) resin.12 For ease
of comparison to the model system, we decided to functionalize
the resin with 4-ethynyl benzyl chloride (7)13 (Scheme 3), and esti-
mated from 1H HR-MAS NMR and gel phase 13C NMR that the alkyl-
ation occurred cleanly with high conversion.
NMR data (CDCl3) for the model compound 5 and the functionalized PEG resin 9
Atoma
1H dH
for 5
HR-MAS dH
for 9
13C dC
for 5
Gel phase dC
for 9
b
1
2
3
4
5
6
7
8
90
900
10
11
12
13
14
—
4.57 (s)
—
—
c
7.32–7.28 (m)
7.37 (t, J = 7.2 Hz)
7.53–7.48 (m)
—
7.06 (d, J = 19.4 Hz)
6.57 (d, J = 19.4 Hz)
1.38 (sept., J = 7.4 Hz)
1.05 (d, J = 7.4 Hz)
1.02 (d, J = 7.4 Hz)
—
128.3
128.7
126.6
138.5
147.5
122.7
11.0
7.33–7.29 (m)
7.48–7.45 (m)
—
7.02 (d, J ꢁ 19 Hz)
6.53 (d, J ꢁ 19 Hz)
1.36–1.34 (m)
1.02 (d, J = 7.1 Hz)
1.00 (d, J = 7.1 Hz)
—
128.0
126.5
138.3
147.1
122.6
10.9
18.0
18.0
17.9
17.9
125.0
137.1
113.5
160.5
55.1
125.0
136.9
113.4
160.4
55.0
7.53–7.48 (m)
6.95 (d, J = 8.6 Hz)
—
7.48–7.45 (m)
6.93 (d, J = 7.7 Hz)
—
3.84 (s)
3.82 (s)
a
See Figure 1 for atom numbering.
b
c
Hidden by the signal for the polymer backbone at ꢁ70 ppm.
Not detectable.
Hydrosilylation of the alkyne functionalized PEG resin 8 with
hydrosilane 4 (Scheme 4) under the reaction conditions applied
in the hydrosilylation of phenyl acetylene14 was highly successful,
as estimated from 1H HR-MAS NMR and gel phase 13C NMR. No al-
kyne signals were detected in the NMR spectra, indicating a high
conversion, and additionally the reaction proceeded in a regio-
and stereoselective manner, yielding solely the desired b-(E)-vinyl
silane 9. The narrow line widths and high resolution in the 1H HR-
MAS NMR spectrum (Fig. 1) demonstrate the power of this tool in
the structure elucidation of immobilized molecules. By taking
advantage of the NMR data obtained for the b-(E)-vinyl silane 5,
it is possible to detect and identify each proton in the spectrum
via its chemical shift and, even more impressive, also the coupling
pattern for some protons (Fig. 1). A comparison of the 1H and 13C
NMR data for 5 and 9 is presented in Table 1.
Whereas the hydrosilylation of terminal alkenes on solid
support is known,5 on-bead hydrosilylation of terminal alkynes
has hitherto not been reported in the literature. The regio- and
stereoselective hydrosilylation of alkynes has features that make
this reaction particularly interesting. Due to the double p-system,
alkynes are more reactive than alkenes3d,e which enables hydrosi-
lylation with bulky hydrosilanes. The range of applicable hydrosil-
anes is much larger for hydrosilylation of alkynes compared to
alkenes, where hydrosilylation is restricted to small and non-bulky
silanes. Additionally, the product vinyl silanes are interesting since
they are reactive toward electrophiles, can partake in the Pd-
catalyzed Hiyama cross coupling6 and have also been successfully
employed in ring-closing metathesis and cross-metathesis
reactions.7
In order to investigate the scope of our method, a variety of dif-
ferent diisopropylsilyl ethers 10–12 were synthesized under stan-
dard silylation conditions15 in yields ranging from 76% to 88%. The
reactivity of silyl ethers 10–12 in hydrosilylations was verified by
successful reactions with phenyl acetylene before they were
In order to demonstrate the reactivity difference between
alkenes and alkynes, we subjected styrene and phenyl acetylene
to hydrosilylation conditions with the bulky hydrosilane 48
(Scheme 2) under the catalysis of Karstedt’s catalyst and the trii-
Table 2
On-bead hydrosilylation of the terminal alkyne 8 with various diisopropylsilyl ethers catalyzed by Pt(DVDS)/1 yielding b-(E)-vinyl silanes17
Entry
Hydrosilane
b-(E)-vinyl silane
OMe
OMe
O
O
O
O
Si
Si
Si
H
1
O
10
13
2
O
Si
H
O
O
11
14
O
Si
3a
Si
H
12
15
a
The vinyl silane was not isolated, but treated immediately with 2,4,5-triisopropylbenzenesulfonylhydrazine, yielding the corresponding saturated silane 15.

P. J. Pedersen et al. / Tetrahedron Letters 49 (2008) 6220–6223
6223
1969, 16, 65–70; (g) Berthon-Gelloz, G.; Schumers, J. M.; De Bo, G.; Marko, I. E. J.
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853–887.
applied in solid-phase hydrosilylations (see Supplementary data).
The regio- and stereoselective hydrosilylations yielded exclusively
the b-(E)-vinyl silanes for all the tested diisopropyl silyl ethers 10–
12 in Table 2, and NMR data confirmed an excellent conversion in
all cases, since no alkyne signals could be detected after comple-
tion of the reactions. In the experiment with silane 12, the result-
ing vinyl silane was further reduced in a one-pot procedure by
treatment with the di-imide generated by thermal decomposition
of 2,4,5-triisopropylbenzenesulfonylhydrazine.16 This tandem pro-
tocol yielded the corresponding saturated silane 15.
In conclusion, we have developed a regio- and stereoselective
hydrosilylation of immobilized terminal alkynes on solid support.
The sterically hindered diisopropyl hydrosilanes afforded b-(E)-vi-
nyl silanes with excellent selectivity using the Pt(DVDS)/1 catalytic
system. The resin-bound compounds were characterized by 1H HR-
MAS NMR and gel phase 13C NMR, illustrating the power and appli-
cability of these tools in solid phase synthesis. We believe this
method will prove valuable not only to future applications of vinyl
silanes in solid-phase synthesis but also as a means of immobiliz-
ing alcohols under selective reaction conditions.
4. The systematical name of the triisobutyl proazaphosphatrane ligand
1 is
2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane and it is
commercially available from Sigma–Aldrich (CAS No. 331465-71-5).
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ratio was determined from 1H NMR. The vinylic protons in the
isomer appear at 5.72 and 6.11 ppm with a characteristic geminal coupling of
2.9 Hz.
10. (a) Fitch, W. L.; Detre, G.; Holmes, C. P. J. Org. Chem. 1994, 59, 7955–7956; (b)
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93, 199–208; (b) Epton, R.; Goddard, P.; Ivin, K. J. Polym. 1980, 21, 1367–1371;
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Acknowledgments
12. (a) Rademann, J.; Grøtli, M.; Meldal, M.; Bock, K. J. Am. Chem. Soc. 1999, 121,
5459–5466; (b) Miranda, L. P.; Lubell, W. D.; Halkes, K. M.; Groth, T.; Grøtli, M.;
Rademann, J.; Gotfredsen, C. H.; Meldal, M. J. Comb. Chem. 2002, 4, 523–529; (c)
SPOCC = Superpermeable organic combinatorial chemistry.; (d) The loading of
hydroxy groups in the VersaBeadsTM VO 2000 (6) resins is 0.94 mmol/g.
13. (a) Available in one step from the corresponding alcohol. See the Supple-
mentary data for the experimental procedure; (b) Landgrebe, J. A.; Rynbrandt,
R. H. J. Org. Chem. 1966, 31, 2585–2593.
We thank Professor Morten Meldal and Dr. Ib Johannsen, Carls-
berg Laboratory, Copenhagen for the donation of VersaBeadsTM VO
2000. We are grateful to the Torkil Holm Foundation and the
Danish Research Council for financial support.
Supplementary data
14. Typical procedure for hydrosilylation of PEG resin 8: The alkyne functionalized
PEG resin 8 (0.85 mmol/g, 1 equiv) was dried under high vacuum (1 mm Hg)
for 24 h, swelled in THF (30 mL per g) and the silane (3–3.5 equiv) was added.
The solution was stirred/agitated for 5 min, before a solution of Pt(DVDS)/ 1
(1 mol % Pt, see Supplementary data for the catalyst preparation) in xylene was
added dropwise. The mixture of beads and reagents was heated to 60 °C and
stirred/agitated for 2.5–53 h under an atmosphere of N2. The solvent and
excess reagents were drained off, the beads were washed with THF, MeCN and
CH2Cl2 (3 ꢂ 60 mL per g), dried under high vacuum (1 mm Hg) for 12 h, and
analyzed by 1H HR-MAS NMR and gel phase 13C NMR.
Supplementary data (experimental procedures, characteriza-
tion data and copies of NMR spectra) associated with this article
can be found, in the online version, at doi:10.1016/j.tetlet.
2008.08.043.
References and notes
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procedure.
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17. Detailed experimental procedures, characterization data and copies of NMR
spectra are available in the Supplementary data.