Scalable Synthesis of Hydrido-Disiloxanes from Silanes: A One-Pot Preparation of 1,3-Diphenyldisiloxane from Phenylsilane

Article abstract of DOI:10.1055/s-0036-1588580

A simple, one-pot, and high-yielding synthesis of 1,3-diphenyldisiloxane is presented. The preparation of similar symmetrical disiloxane materials is also accomplished with this same protocol. This mechano-chemical procedure is efficient and highly scalab

Full text of DOI:10.1055/s-0036-1588580

SYNTHESIS
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Scalable Synthesis of Hydrido-Disiloxanes from Silanes: A One-Pot
Preparation of 1,3-Diphenyldisiloxane from Phenylsilane
Joseph A. Buonomo
Carter G. Eiden
Courtney C. Aldrich*
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University of Minnesota, Department of Medicinal Chemistry,
Weaver-Densford Hall, 308 Harvard St. SE Minneapolis, MN
55455, USA
aldri015@umn.edu
Received: 02.09.2017
Accepted after revision: 06.09.2017
Published online: 26.09.2017
methods to produce DPDS and other di- and tetra-substi-
tuted hydrido-disiloxanes from silanes are complicated by
over-oxidation. These limitations hamper the usage of
DPDS and prevent the investigation and development of ad-
ditional hydrido-disiloxanes. We were thus prompted to
develop an experimentally simple, safe, and high-yielding
reaction to access this important, yet largely unexplored
class of compounds (Scheme 1).
DOI: 10.1055/s-0036-1588580; Art ID: ss-2017-n0283-psp
Abstract A simple, one-pot, and high-yielding synthesis of 1,3-di-
phenyldisiloxane is presented. The preparation of similar symmetrical
disiloxane materials is also accomplished with this same protocol. This
mechano-chemical procedure is efficient and highly scalable, furnishing
a convenient route to hydrido-disiloxanes from widely accessible com-
mercially available silanes.
a. 2.0 equiv CuCl2
0.1 equiv CuI
Et2O, 23 °C
Key words siloxane, silane, chlorination, copper, ball-milling, one-pot
O
SiH3
Si
Si
H2
H2
b. H2O, 0 °C
The reduction of phosphine oxides with silanes occurs
with high specificity and fidelity, and represents one of the
most useful methods for the synthesis of phosphines. The
1a
one-pot, 93% yield
2a
Scheme 1 Convenient and scalable synthesis of 1,3-diphenyldisiloxane
2a)
1
(
chemoselectivity of this process also allows for in situ recy-
cling of phosphine oxide by-products to afford catalytic ver-
sions of the Wittig, Staudinger, and Mitsunobu reactions,
The synthesis of silanols and disiloxanes is well known
2
among many others. However, silane-mediated reduction
as these compounds have applications in a broad range of
4
of phosphine oxides generally requires both elevated tem-
peratures (80–110 °C) and additives, thereby substantially
limiting the substrate scope. We recently discovered that
hydridophenyl-disiloxanes facilitate reduction of phosphine
chemistry, from the synthesis of therapeutics to liquid
5
crystals. Transition-metal-catalyzed oxidation of precursor
silanes is the most common strategy to prepare silanols and
6
disiloxanes, but these methods lead to complete oxidation
3
oxides in a very rapid manner. Subsequent testing of mul-
of the silane to either a mono-, di-, or tri-silanol depending
7
tiple hydridophenyl-disiloxanes revealed that 1,3-di-
phenyldisiloxane (DPDS) is the most reactive, promoting
on the number of Si–H bonds. One report of an In(III)-cata-
lyzed direct oxidation suggests that the mono-oxidation
3
8
rapid reduction under ambient conditions. DPDS is a bench
product can be obtained; however, this reaction was only
stable and innocuous reagent that can provide two equiva-
lents of phenylsilanol through in situ hydrolysis. We have
shown that DPDS is the mildest reagent available for reduc-
tion of phosphine oxides to phosphines, combining the che-
moselectivity of silanes with the low temperature capabili-
performed on a small scale, and the reaction was not ex-
tended to phenylsilane. The generation of a full equivalent
of hydrogen gas is also a safety concern. Hydrido-disilox-
anes have historically been prepared through an alternative
two-step sequence involving preparation and isolation of a
mono-halogenated silane followed by hydrolysis (Scheme
1d
ties of much harsher methodologies. It can be used both
to prepare phosphine ligands with extremely diverse scaf-
folds as well as to recycle phosphine oxides in ambient cata-
9
2). Synthesis of the intermediate halosilanes is challenging,
1
0
as is evident by the lack of their commercial availability,
with multiple methods furnishing complex mixtures.
3
11
lytic phosphine redox reactions. Unfortunately, current
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Synthesis
J. A. Buonomo et al.
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Consequently, much effort has been put into the synthesis
of mono-halogenated silanes, and two complimentary ap-
proaches have emerged that address previous synthetic de-
ficiencies. The first of these employs concentrated HBr to
displace a phenyl group on a silane with a bromide,12 while
the second approach uses copper(II) chloride to directly
tries 2 and 3), and a combination of these substitution pat-
terns was also tolerated as 1,3-dimethyl-1,3-diphenyldi-
siloxane 2d was synthesized in 85% yield (entry 4).
Table 1 Direct Synthesis of Symmetrical Disiloxanes from Commer-
cially Available Silanes
13
13b
chlorinate hydrido-silanes. Zhang and co-workers fur-
ther improved on the latter copper(II) chloride halogena-
tion through ‘ball-milling’. Herein, we report a one-pot ex-
perimental method for the preparation of DPDS and related
hydrido-disiloxane reagents in high purity from commer-
cially available silanes. This scalable procedure furnishes
a. 2.0 equiv CuCl2
0.1 equiv CuI
Et2O, 23 °C, 2 h
R3Si
H
R3Si
O
SiR3
b. H2O, 0 °C, 15 min
1
2
Entry
1
Product
Yield (%)a
9,13
hydrido-disiloxanes in improved yield,
and substantially
lowers the time required to obtain product with only a sin-
gle purification step.
93b,c
2a
O
Si
Si
H2
H2
Previous Methods: Two purifications necessary
4
"H-"
H2O
H2O
H2
Si
H2
Si
2
2
R
R
SiCl3
SiH3
2
2
R
R
SiH2
Cl
R
R
O
O
R
R
2
3
2b
2c
O
90
Si
Si
H
H
Ph
Ph
4
CuCl2
cat. CuI
C6H13
O
C6H13
H2
Si
H2
Si
85d
Si
H
Si
H
SiH2
Cl
2
2
This Work: Only one purifcation
4
2d
O
85
Si
Si
a. 4 CuCl2
cat. CuI
H
H
H2
Si
H2
Si
Me
Me
2
R
SiH3
R
O
R
b. H2O
a
Isolated yield of two trials at 15 mmol scale.
Yield was 93% before distillation (>95% purity) and 88% after distillation
99% purity).
Yield on 90 mmol (10 gram) scale was 88% (with >95% purity).
This reaction required 5 hours for step ‘a’ before filtration onto ice.
b
Scheme 2 Synthesis of hydrido-disiloxane materials from literature
(
and this work
c
d
The synthesis of DPDS begins with the complexation of
Our efficient approach utilizes mechano-chemistry in
CuCl and catalytic CuI in diethyl ether for 30 min in the
presence of either chrome or ceramic spheres. Phenylsilane
is then added and the reaction is ball-milled at 350 rpm at
an effort to significantly reduce the reaction time from
more than 8 hours (magnetic stirring) to only 1.5 hours.
During the reaction, CuCl2 is reduced to a Cu(I) species,
2
ambient temperature under air with an overhead stirrer for
which coats the CuCl particles and hinders progression of
the reaction. The physical grinding during the comminu-
2
1
1.5 h until 100% conversion is noted by H NMR analysis to
afford the intermediate chlorophenylsilane. The reaction
mixture is filtered directly onto ice chips (Figure S1, Sup-
porting Information) and extracted with diethyl ether to af-
ford DPDS in 93% percent yield and approximately 95% pu-
rity, which is sufficient for most applications. Distillation
under high vacuum can be performed to provide DPDS in
tion process ensures CuCl is continually exposed. As such,
the balls utilized should be fairly large in diameter (at least
½ inch) to avoid the inhibition of the reaction through
2
buildup of byproduct on the heterogeneous CuCl . We ex-
2
plored different materials for the ball-milling procedure
and found ceramic spheres were preferred over chrome
spheres since the reaction yield was compromised when
metal balls were reused multiple times (Table S1, Support-
ing Information). This is likely due to the inert nature of ce-
ramic, as this material is chemically stable to the reaction
conditions. Another advantage with respect to laboratory
scale reactions utilizing transition-metal catalysis is that
>
99% purity and 88% overall yield when higher purity is re-
quired (Table 1, entry 1). The reaction is scalable and does
not require increased reaction times to obtain purified
product. For example, DPDS is obtained in 88% yield on a 10
gram scale in less than three hours. The reaction conditions
can be extended to secondary arylsilanes as well as alkyl-
silanes, as diphenylsilane and n-hexylsilane were readily
converted into 1,1,3,3-tetraphenyldisiloxane 2b and 1,3-di-
n-hexyldisiloxane 2c in 90% and 85% yield, respectively (en-
the CuCl -mediated mechano-chemical method does not
2
produce a stoichiometric amount of hydrogen gas, and all
byproducts are simply washed away with cold water. In ad-
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Synthesis
J. A. Buonomo et al.
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dition, this protocol can be implemented in standard labo-
ratory glassware, rather than requiring specialized ball-
milling equipment.
After distillation, a colorless oil was obtained (4.55 g, 19.8 mmol, 88%
yield). Analytical data reported below is for material that was not ad-
ditionally distilled.
1
H NMR (CDCl , 500 MHz): δ = 7.53 (d, J = 7.6 Hz, 4 H), 7.37 (t, J =
We have described an efficient one-pot, mechano-
chemical procedure for the synthesis of hydrido-disilox-
anes. The high yield, simple experimental set-up, and short
reaction time are all ideal for laboratory scale preparations
of hydrido-disiloxanes, which are valuable compounds for
the chemoselective reduction of phosphine oxides. The
ability to easily prepare useful quantities of hydrido-
disiloxanes is expected to not only make the newly charac-
terized reducing agent DPDS highly accessible for both
phosphorous recycling and phosphine synthesis, but also to
unleash the full potential of this entire class of underex-
plored reagents through stimulating further investigations
into their unique reactivity.
3
7.6 Hz, 2 H), 7.32 (t, J = 7.2 Hz, 4 H), 5.06 (s, 4 H).
13
C NMR (CDCl , 126 MHz): δ = 134.10, 130.54, 128.13.
3
HRMS (ESI): m/z [M + Na] calcd for C12H14NaOSi : 253.0475; found:
2
253.0471.
1
,1,3,3-Tetraphenyldisiloxane (2b)14,15
[
CAS Reg. No. 15545-80-9]
The procedure for 2a was followed on 15.0 mmol scale using ten
inch diameter balls. The title compound 2b was obtained.
Yield: 2.58 g (6.75 mmol, 90%); colorless/white solid; mp 48–49 °C
5
15
[
Lit. mp. 46–49 °C (ethanol)].
1H NMR (CDCl
, 500 MHz): δ = 7.48 (d, J = 6.9 Hz, 8 H), 7.34 (t, J =
.4 Hz, 4 H), 7.27 (t, J = 7.7 Hz, 8 H), 5.52 (s, 2 H).
3
7
13
C NMR (CDCl , 126 MHz): δ = 134.33, 130.24, 127.96.
3
CuCl2 was purchased from Strem and used as received. Phenylsilane
and diphenylsilane were purchased from Oakwood Chemical and
used as received. CuI, hexylsilane, methyl(phenyl)silane, and diethyl
ether were purchased from Sigma–Aldrich and used as received. All
reagents were stored in a light-shielding dessicator. All reactions at 15
mmol or larger scale were performed using the mechano-chemical
procedure employing degreased balls from VXB.com (see the Sup-
porting Information) and an IKA RW-16-Basic overhead stirring appa-
ratus. NMR spectra were recorded with a Bruker Avance 500 MHz
HRMS (ESI): m/z [M + H] calcd C24H23OSi2: 383.1282; found:
383.1280.
,3,-Di-n-hexyldisiloxane (2c)8
1
[
CAS Reg. No. 1203611-82-8]
The procedure for 2a was followed on 15.0 mmol scale using ten
inch diameter balls. Additional purification of this product, if need-
5
ed, was achieved by distillation at reduced pressure (bp 76 °C at 580
mTorr) to give the title compound 2c.
1
spectrometer operating at 500 MHz for H signals and 126 MHz for
1
3
C signals. NMR chemical shifts are reported in ppm in reference to
Yield: 1.57 g (6.38 mmol, 85%); colorless to pale-yellow oil.
1
the residual solvent peak CDCl (δ = 7.26 ppm for H and δ = 77.1 ppm
for C) as an internal standard.
1
3
H NMR (CDCl , 500 MHz): δ = 4.52 (t, J = 2.6 Hz, 4 H), 1.36–1.22 (m,
3
13
20 H), 0.82 (t, J = 6.9 Hz, 6 H).
1
3
C NMR (CDCl , 126 MHz): δ = 32.34, 31.55, 22.92, 22.54, 14.47,
3
1
,3-Diphenyldisiloxane [17962-59-3] (2a);9a Typical Procedure
1
4.10.
On the benchtop, under air, a two-necked 500 mL round-bottom flask
equipped with thirty-five 5 inch diameter balls, was charged with
CuCl (12.1 g, 90 mmol, 2.0 equiv), CuI (857 mg, 4.5 mmol, 0.1 equiv),
HRMS (ESI): m/z [M + Na] calcd C12H30NaOSi : 269.1727; found:
2
2
69.1732.
2
and Et O (60 mL). An overhead stirrer with a flat paddle was fitted to
the reaction vessel and the mixture was stirred at 30% speed (ca. 350
rpm) for 30 min. The stirrer was stopped and phenylsilane (5.54 mL,
2
1
,3-Dimethyl-1,3,-diphenyldisiloxane (2d)16
[CAS Reg. No. 1203611-82-8]
4
5 mmol, 1.0 equiv) was added down the walls of the flask; a color
The procedure for 2a was followed on 15.0 mmol scale using ten
change was noted immediately (see photographs in the Supporting
Information). Stirring at 30% speed was resumed and allowed to pro-
ceed for the duration of the reaction. The progress of the reaction was
easily monitored by H NMR spectroscopic analysis. Upon comple-
tion, the reaction mixture was filtered through a Büchner funnel di-
rectly onto ice (45 g, 2.5 mol) to remove copper salts and the balls,
5
inch diameter balls. Additional purification of this product, if need-
ed, was achieved by distillation at reduced pressure (bp 102 °C at 800
16b
mTorr; Lit. bp 105 °C at 1 Torr) to give the title compound 2d.
1
Yield: 1.64 g (6.35 mmol, 85%); colorless to pale-yellow oil.
1H NMR (CDCl
, 500 MHz): δ = 7.40 (dt, J = 7.9, 1.4 Hz, 4 H), 7.25–7.19
3
and the cake was washed with additional Et O (30 mL). The mixture
(m, 6 H), 4.98 (dd, J = 2.9, 1.1 Hz, 2 H), 0.27 (d, J = 3.1 Hz, 6 H).
2
was swirled by hand every 5 min until the ice melted (15–45 min).
The layers were separated and the organic layer was washed with
cold de-ionized water (2 × 60 mL). The organic layer was then dried
13
C NMR (CDCl , 126 MHz): δ = 137.75, 134.04, 130.55, 128.55, 0.00.
3
HRMS (ESI): m/z [M + Na] calcd C14H18NaOSi : 281.0788; found:
2
281.0799.
with MgSO and evaporated at 40 °C at reduced pressure (22 Torr) to
4
remove trace unreacted phenylsilane. The title compound 2a was ob-
tained as a colorless to pale-yellow oil (4.80 g, 20.9 mmol) in 93%
yield. The material was approximately 95% pure by H NMR analysis.
1
Acknowledgment
If necessary, the product can be further purified by distillation at re-
duced pressure (bp 76 °C at 580 mTorr; Lit. bp 85 °C at 800 mTorr).
This work was supported by the University of Minnesota College of
Pharmacy, an NSF Graduate Research Fellowship to J.A.B. (GRFP:
9a
00039202), a Bighley Fellowship to J.A.B. (UMN-COP), and a Chemi-
cal-Biology Interface Training Grant to C.G.E. (T32-GM008700).
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Supporting Information
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Omar, M. M. J. Am. Chem. Soc. 2005, 127, 11938. (c) Matsuo, T.;
Kawaguchi, H. J. Am. Chem. Soc. 2006, 128, 12362.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588580.
S
u
p
p
ortioIgnfrm oaitn
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p
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–D