Sterically directed iridium-catalyzed hydrosilylation of alkenes in the presence of alkynes

Article abstract of DOI:10.1021/ol5000549

A selective iridium catalyzed hydrosilylation of alkenes in the presence of more reactive alkynes is described. By utilizing [IrCl(COD)]₂ in the presence of excess COD, hydrosilylation of alkenes and alkynes with ethynylsilanes is achieved with

Full text of DOI:10.1021/ol5000549

Letter
pubs.acs.org/OrgLett
Sterically Directed Iridium-Catalyzed Hydrosilylation of Alkenes in
the Presence of Alkynes
Jill A. Muchnij, Farai B. Kwaramba, and Ronald J. Rahaim*
107 Physical Sciences 1, Department of Chemistry, Oklahoma State University, Stillwater, Oklahoma 74078, United States
S
* Supporting Information
ABSTRACT: A selective iridium catalyzed hydrosilylation of
alkenes in the presence of more reactive alkynes is described.
By utilizing [IrCl(COD)]2 in the presence of excess COD,
hydrosilylation of alkenes and alkynes with ethynylsilanes is
achieved with good chemo- and regioselectivity. This approach goes against the traditional reactivity trends of platinum and
rhodium catalysts and allows access to highly substituted silicon alkyne tethers.
he application of temporary tethers1 has been a versatile
approach to facilitate rapid access to biologically active
Scheme 1. Alkynyl-Silicon Linkers
T
complex molecules and building blocks. A variety of temporary
tethers2 have been developed, ranging from silicon,3 boron,4
magnesium,5 phosphorus,6 and esters.7 The advantages of
tethered reactions are increased reaction rates between the
coupling partners and high levels of regio- and stereoselectivity.
Of the different approaches developed, temporary silicon tethers
have been the most commonly utilized approach. Silicon tethers
are versatile in that large assortments of silicon reagents are
available and the tether can be prepared under standard
conditions in high yields. They are tolerant to a range of reaction
conditions, but can be efficiently cleaved via subjection to
Tamao−Fleming oxidation8 or Hiyama cross-couplings.9 The
most common temporary silicon tethers are based on disiloxane
and siloxane structural motifs.
We have initiated a program in the development of dual10/
synergistic11 catalysis utilizing temporary tethers for applications
in library development. As part of this endeavor we required a
modular protocol to link a variety of terminal alkynes to an array
of functionalized fragments. Silyl alkynes are ideal temporary
tethers because they are easily and efficiently prepared from
metal acetylides,12 are stable under most standard reaction
conditions, but can be easily cleaved under nucleophilic fluorine
conditions.13 Therefore, what is required is an approach to link
the silyl alkyne to the second coupling partner through the
silicon. This has previously been accomplished with alkenyl
alcohols for subsequent applications in enyne-metathesis
reactions (RCM) through formation of an alkynyl siloxane
(Scheme 1a).14 A drawback of the alkynyl siloxane tether is the
instability of the siloxane, which makes isolation problematic. To
complement this approach and satisfy our requirement for a
temporary silicon linker that could be carried through multiple
synthetic steps, we sought to develop a method for an
alkynylsilane linker.
or alkyne (Scheme 1c). To the best of our knowledge, a method
for the selective hydrosilylation of olefins in the presence of an
alkyne has not been reported. This gap is most likely the result of
the higher reactivity of the π-basic alkyne. However, there has
been a spattering of reports demonstrating transition metal
catalyzed silane alcoholysis in the presence of an alkyne (Scheme
1b).17 Selective hydrosilylation of one alkene in the presence of
another has been accomplished using either a directing group or
steric bias. Based on these results, we speculated that it may be
possible to override the inherent electronic bias for the more
reactive alkyne through a steric directed approach. Prototypical
transition metals that have been employed in hydrosilylation
reactions are Pt,18 Rh,19 Pd,20 Ru,21 Ir,22 and Fe.23 As the starting
point to this investigation we selected iridium as the metal of
choice based on its selectivity in catalyzing hydrosilylation
reactions of allyl substrates24 in addition to iridium catalysts
demonstrating chemo-25 and regioselectivity26 by favoring steric
over electronic control.
Investigation into the feasibility of this approach began with
optimization of the conditions for hydrosilylation of allyl benzyl
ether (2a) with alkynylsilane (1a) (Table 1). The conditions
Hydrosilylation15 of double and triple bonds has proven to be
an important reaction/tool in organic synthesis.16 The versatility
of hydrosilylation reactions conducted with high levels of regio-
and stereocontrol and functional group compatibility made this a
desirable approach to connect an alkynylsilane linker to an olefin
Received: January 7, 2014
Published: February 19, 2014
© 2014 American Chemical Society
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Letter
a
Table 1. Optimization of Hydrosilylation Reaction
b
c
entry
catalyst
ligand (loading)
time (h)
% conv
% yield
d
1
2
3
4
5
6
7
[IrCl(COD)]2
[IrCl(COD)]2
[IrCl(COD)]2
[IrCl(COD)]2
[IrCl(COD)]2
[IrCl(COD)]2
[IrCl(COD)]2
[IrCl(COD)]2
[IrCl(COD)]2
[IrCl(COD)]2
[IrOMe(COD)]2
IrCl3
COD (0.5 equiv)
COD (1 equiv)
COD (4 equiv)
none
4
87
86
98
72
70
90
70
100
86
100
10
0
n.d.
n.d.
88
n.d.
55
47
25
89
78
77
n.d.
n.d.
0
4
4
16
19
4
Limonene (4 equiv)
1,10-phen (2 mol %)
2,2′-Bipyr (1 mol %)
COD (0.5 equiv)
COD (0.5 equiv)
COD (0.5 equiv)
COD (4 equiv)
COD (4 equiv)
none
4
e
8
19
0.33
0.33
24
24
2
f
9
fg
10 ,
11
12
13
14
15
h
H2PtCl6
100
100
100
I
h
Karstedt
none
2
0
h
[(Ph)3P]3RhCl
none
16
0
a
b
Conditions: 1 mmol silane (1a), 1 mmol olefin (2a), 0.5 mol % catalyst, ligand, rt; all liquid reagents were degassed. Monitored by GC and based
c
d
e
on consumption of 2a. Isolated by flash chromatography. n.d. = not determined. 0.1 mol % [Ir(COD)Cl]2, reaction 0.5 M in 1,2-dichloroethane.
f
g
h
I
MW, 60 °C. 1 M in 1,2-dichloroethane. Consumption of 1a by GC. Pt2[(Me2SiCHCH2)2O]3.
developed for iridium catalyzed hydrosilyation of allyl halides
with chlorodimethylsilane were used as the starting point.27 The
desired silylation product (3a) was formed under neat conditions
with 0.5 mol % [IrCl(COD)]2, but full conversion could only be
accomplished when a large excess of coadditive ligand 1,8-
cyclooctadiene (COD) was used (Table 1, entries 1−4). To
obtain reproducible results and high yields of 3a, it was
determined that all liquid reagents needed to be degassed prior
to use. Screening alternative diene, olefin, and amine ligands
(entries 5−7) resulted in decreased conversion of starting
effect on yield or reaction times when electron-donating or
-withdrawing functional groups were incorporated into the aryl
alkynylsilanes (entries 3−4). However, the presence of a
conjugated olefin resulted in prolonged reactions of 44−48 h
(entries 8−9). Standard alcohol protecting groups were well
tolerated (entries 7 and 9), and the steric hindrance of a tert-butyl
group (entry 10) did not inhibit the reaction. Variation of the
alkene demonstrated that the system tolerates an acid labile
tetrahydropyran allyl ether (entry 11), an epoxide (entry 14), the
reactive allyl bromide (entry 15), an ester (entry 17), and a
primary tosylate (entry 18). While allyl bromide formed the
product (3ae) in near-quantitative yield, allyl acetate (entries
12−13) only afforded moderate yields of the hydrosilylation
product with the remaining mass balance being unreacted allyl
acetate. The diminished yields for the allyl acetate may be due to
coordination of the carbonyl to the electrophilic iridium.29
Subjection of allyl alcohol (entry 19) to the reaction conditions
afforded a complex mixture,30 whereas styrene was completely
unreactive (entry 20).31−33 Hydrosilylation of (E)-1-(allyloxy)-
but-2-ene was chemoselective for the terminal olefin over the
internal disubstituted alkene (entry 21) with chelation to the
catalyst contributing to the poor conversion.
materials to product or promoted undesired side reactions.28
A
solvent screening established that the amount of COD additive
could be decreased, from 4.07 to 0.5 equiv when a nonpolar
solvent (e.g., ClCH2CH2Cl, CH2Cl2, or toluene) was used, but at
the cost of prolonged reaction times (entry 8) and inconsistent
conversion to products in substrate screenings. Attempts to
shorten reactions times further under thermal microwave
irradiation resulted in high conversion in less than 20 min
(entries 9−10). Unfortunately, under the thermal conditions
undesirable reaction pathways became more favorable, diminish-
ing the yield of the desired product. To establish the original
hypothesis that the feasibility of this reaction was reliant upon the
use of an iridium catalyst, Speier’s (H2PtCl6), Karstedt’s
(Pt2 [(Me2 SiCHCH2 )2 O]3 ), and Wilkinson’s
([(Ph)3P]3RhCl) catalysts were screened (entries 13−15). As
expected, these classical platinum and rhodium catalysts
promoted the silyl alkyne to react with itself, affording none of
the desired hydrosilylation product.
With the optimized conditions in hand, 0.5 mol % [IrCl-
(COD)]2 and 4.07 equiv of COD at room temperature with all
substrates/reagents degassed, substrate screening was initiated
(Table 2). In all of the terminal alkenes tested, only anti-
Markovnikov selectivity was detected. Hydrosilylation of allyl
benzyl ether (2a) with various alkynylsilanes (Table 2, entries 1−
10) occurred in moderate to high yields regardless of whether the
substituent on the alkyne was aliphatic or aromatic. There was no
Terminal alkynes34 were examined next (Table 3). Phenyl-
acetylene was efficiently hydrosilylated with both an aromatic
and aliphatic alkynylsilane (entries 1−2). Electron-donating and
-withdrawing groups on the phenylacetylene (entries 3−4) had
no effect on the yield, but the electron-donating methoxy group
afforded a mixture of regioisomers.35 Subjection of a diyne to the
reaction conditions afforded a mixture of mono- and dihydro-
silylation products with E-selectivity. Increasing the concen-
tration of the silane to 2 equiv increased the overall yield but did
not affect the ratio of mono- to dihydrosilylation (entries 5−6).
Hydrosilylation of a sterically congested tert-butyl acetylene
(entry 7) occurred without incedent. The system was chemo-
selective for the terminal alkyne of an enyne (entry 8) and in the
presence of a nitrile (entry 9), although the nitrile did inhibit full
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Table 2. Substrate Screening between Alkynylsilanes and
Alkenes
Table 3. Substrate Screening between Alkynylsilanes and
a
a
Alkynes
a
Conditions: 1 equiv of 1a or 1e (1 mmol), 1 equiv of 4a−l (1 mmol),
0.5 mol % [IrCl(COD)]2, 4.07 equiv of COD (0.5 mL), rt, all reagents
b
c
degassed. Determined by GC. Average isolated yield of two runs.
d
e
Ratio determined by 1H NMR of the crude reaction. Used 2 equiv of
1a.
conversion. Examination of conjugated carbonyls revealed that
deactivated alkynes require extended reaction times and were
low yielding (entries 10−11), whereas the alkyne of propargyl
acrylate (entry 12) underwent hydrosilylation in high yield but
afforded a mixture of E and internal regioisomers.36 As with allyl
alcohol (Table 2, entry 19), propargyl alcohol (Table 3, entry 13)
also afforded a complex mixture,37 but simple protection of the
alcohol with a TBS group (entry 14) afforded the desired
hydrosilylation product in high yield, favoring the E isomer.
In summary, by employing a sterically controlled approach we
were able to hydrosilylate alkenes with alkynylsilanes under
iridium catalysis. The system demonstrated good chemo- and
regioselectivity, allowing efficient and easy access to highly
functionalized alkynylsilane tethers. Application of these tethers
in dual/synergistic catalysis will be reported in due course.
ASSOCIATED CONTENT
* Supporting Information
Experimental details, product characterization data, and further
discussion. This material is available free of charge via the
Internet at http://pubs.acs.org.
■
a
Conditions: 1 equiv of 1a−j (1 mmol), 1 equiv of 2a−k (1 mmol),
S
0.5 mol % [IrCl(COD)]2, 4.07 equiv of COD (0.5 mL), rt, all reagents
degassed. Determined by GC. Average isolated yield of two runs. A
complex mixture was obtained. 1a and 2j were isolated again in near-
quantitative yield.
b
c
d
e
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Letter
Andersson, P. G., Munslow, I. J., Eds.; Wiley-VCH: Weinheim, 2008; pp
87−105.
AUTHOR INFORMATION
■
Corresponding Author
(17) (a) Miller, R. L.; Maifeld, S. V.; Lee, D. Org. Lett. 2004, 6, 2773−
2776. (b) Scott, C. N.; Wilcox, C. S. J. Org. Chem. 2010, 75, 253−256.
(18) (a) Marko, I. E.; Sterin, S.; Buisine, O.; Mignani, G.; Branlard, P.;
Tinant, B.; Declercq, J. P. Science 2002, 298, 204−207. (b) Lewis, L. N.;
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*E-mail: Rahaim@okstate.edu.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(20) (a) Junge, K.; Wendt, B.; Enthaler, S.; Beller, M. ChemCatChem
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We thank Oklahoma State University for the generous support.
We thank the reviewers for helpful critiques. Mass spectrometry
analyses were performed in the DNA/Protein Resource Facility
at Oklahoma State University, using resources supported by the
NSF MRI and EPSCoR programs (DBI/0722494).
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