A recyclable Ru(CO)Cl(H)(PPh3)3/PEG catalytic system for regio- and stereoselective hydroboration of terminal and internal alkynes

Article abstract of DOI:10.1002/adsc.201800409

This paper reports on the first repetitive batch selective hydroboration of terminal and internal alkynes in a series of poly(ethylene glycols) (PEGs), used as solvents and media for the immobilization of a Ru(CO)Cl(H)(PPh₃)₃ catalyst. The system based on 2 mol% of Ru?H complex and poly(ethylene glycol) with α-methyl/ω-trimethylsilyl ending groups (Mw=2000) was found to be the most efficient, and was able to carry out over 19 complete runs with the Z-addition of pinacolborane to the phenylacetylene. With the use of one portion of the developed catalytic system, the hydroboration of five different alkynes was performed consecutively, and led to five different products being obtained with high yields and purities. The developed strategy was characterized by high TON values and it was found to be the best recyclable protocol, leading to alkenyl boronates in all reported cases. (Figure presented.).

Full text of DOI:10.1002/adsc.201800409

Title: A recyclable Ru(CO)Cl(H)(PPh3)3/PEG catalytic system for
regio- and stereoselective hydroboration of terminal and internal
alkynes
Authors: Jakub Szyling, Adrian Franczyk, Kinga Stefanowska, and
Jedrzej Walkowiak
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201800409
Link to VoR: http://dx.doi.org/10.1002/adsc.201800409

10.1002/adsc.201800409
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
A recyclable Ru(CO)Cl(H)(PPh3)3/PEG catalytic system for
regio- and stereoselective hydroboration of terminal and
internal alkynes
Jakub Szyling,a, b Adrian Franczyk,a Kinga Stefanowskaa, b and Jędrzej Walkowiak*a
a
Centre for Advanced Technologies, Adam Mickiewicz University, Umultowska 89c, 61-614 Poznan, Poland,
Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznan, Poland.
b
*e-mail: jedrzej.walkowiak@amu.edu.pl.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. This paper reports on the first repetitive batch With the use of one portion of the developed catalytic
selective hydroboration of terminal and internal alkynes in a system, the hydroboration of five different alkynes was
series of poly(ethylene glycols) (PEGs), used as solvents and performed consecutively, and led to five different products
media for the immobilization of a Ru(CO)Cl(H)(PPh3)3 being obtained with high yields and purities. The developed
catalyst. The system based on 2 mol% of Ru-H complex and strategy was characterized by high TON values and it was
poly(ethylene glycol) with α-methyl/ω-trimethylsilyl ending found to be the best recyclable protocol, leading to alkenyl
groups (Mw = 2000) was found to be the most efficient, and boronates in all reported cases.
was able to carry out over 19 complete runs with the Z-
addition of pinacolborane to the phenylacetylene.
Keywords: Hydroboration; alkynes; poly(ethylene
glycols); catalyst recycling; immobilization; ruthenium
Introduction
Transition-metal (TM) catalyzed hydroboration of
alkynes provides a straightforward, 100% atom
economical, and simple method for the synthesis of
unsaturated organoboron compounds which are one
of the most versatile intermediates currently available
in organic chemistry transformations (coupling
reactions, deborylation processes).[1-5] In this context,
their efficient and selective syntheses are of great
importance.
products by TM species and problems with the
recovery and reuse of the catalyst are the biggest
drawbacks to this approach. Additionally, multi-step
and time-consuming product isolation protocols are
involved which is often not favourable from an
economic and environmental point of view,
especially in a gram or multi-gram scale synthesis.[12]
For these reasons, effective methods for catalyst
immobilization, which will build long-lasting and
efficient catalytic systems, are still a challenge. The
new synthetic strategies that utilize alkyne
hydroboration and more environmentally friendly
conditions, through recycling of catalysts (e.g.
nanoparticles) in organic solvents, have already been
studied.[13]
In recent years, the application of green solvents
(e.g. water,[14] fluorous media,[15] ionic liquids
(ILs)[16] or the supercritical CO2 (scCO2) which has
previously been described by us[17]) in the synthesis
of alkenyl boronates in repetitive batches has
attracted increasing interest (Scheme 1).
There are several catalytic and non-catalytic
methods leading to alkenyl boronates (e.g. the
addition of diboron compounds to alkynes,[6]
codimerization of vinyl boronates with alkynes,[7]
8]
metathesis[5b,
or borylative coupling[9]) but
hydroboration is the most versatile and frequently
used. It occurs in a radical and non-catalytic manner,
but, to obtain a specific isomeric product, the
application of
a
molecular catalyst is often
required.[10]
The hydroboration of alkynes in the presence of
TM-complexes is a well-established process.[11] In
most cases the process occurs under homogeneous
conditions, which provides high selectivity. However,
a large amount of volatile organic solvents (VOS) is
required to ensure appropriate solubility of the
reagents and catalysts. The contamination of the
The repetitive batch hydroboration of alkynes in
water or perfluorinated methylcyclohexane occurred
with low TON (46 and 474) within 5 and 2 cycles. A
discussion on the process selectivity in appropriate
cycles is not provided.
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800409
Advanced Synthesis & Catalysis
Scheme 1. Alkyne hydroboration in green solvents. under repetitive batch mode.
On the other hand, the application of ILs in
The hydroboration of the carbon-carbon triple
bonds (C≡C) in PEGs has never been explored.
repetitive hydroboration has been studied in only one
paper by Vaultier et al.[16] They tested RhCl(PPh3)3
(0.8 mol%) immobilized in [BMIM][Cl][ZnCl2] in
the hydroboration of n-hexyne, which was recycled
six times. The activity of this system decreased by
the 2ndcycle, indicating low efficiency.
To date, only two reports on the hydroboration of
carbon-carbon double bond (C=C) in PEGs have
been published. One is related to the hydroboration of
internal olefins in the presence of PEG (Mw = 400) by
diborane generated in situ and the subsequent
isomerization of alkylboranes, followed by their
oxidation to alcohols.[26] In the second, the catalytic
cartridge system based on a Rh(acac)(CO)2 complex,
with PEG-modified phosphine ligand and scCO2 in
Recently, we have applied scCO2 as a solvent and
extractant in the hydroboration of alkynes in the
presence of
a self-dosing Ru(CO)Cl(H)(PPh3)3
catalyst. The 2 mol% loading of the catalyst
permitted us to carry out 19 runs, with excellent
yields up to the 16th cycle. This resulted in a system
with TON 886, which was the highest among all
reported.[17]
sequential
hydroboration/
hydroformylation/
hydrogenation, and, again the hydroboration reaction/
extraction method was used.[27]
Taking into account the solvent properties of PEGs,
the lack of reports on the hydroboration of alkynes in
these media and our experience in the synthesis and
application of unsaturated organoboron or silicon
compounds,[5a, 7b, 9b, 17, 28] in this work, we decided to
develop an efficient, and environmentally friendly
These results encouraged us to use other green
solvents such as poly(ethylene glycols) (PEGs) for
the hydroboration of alkynes.
PEGs, due to their unique physicochemical
properties (low melting points, negligible vapour
pressure, high stability in both acidic and basic media, protocol for the hydroboration of alkynes in PEGs in
miscibility with polar and non-polar organic,
organometallic or even inorganic compounds, lack of
toxicity and low price[18]), are commonly used in
many branches of science and industry.[19] Recently,
several examples of their applications as solvents for
TM-catalyzed reactions, such as hydrogenation,[19c, 20]
repetitive batches.
Our goal was to build a new strategy leading to a
regio- and stereoselective synthesis of alkenyl
boronates in which i) homogeneity of the process was
maintained, ii) pure products were isolated from the
catalyst in a one-step separation protocol, iii) a
molecular catalyst and polymeric solvent were reused,
iv) a gram-scale synthesis was performed and v) the
scope and limitations of proposed procedure were
determined.
C-C
bond
formations,[21]
Buchwald-Hartwig
amination,[22] and polymerization[23] have been
described. The moderate polarity of PEGs allows the
immobilization of polar, organometallic and
molecular catalysts and their effective recycling and
reuse.[24] Therefore, in contrast to perfluorinated
solvents, scCO2 or water, modification of the catalyst
structure is not needed to increase its affinity to a
solvent. Therefore, PEGs are an excellent alternative
to toxic volatile organic solvents. Moreover,
preparation of PEGs via ethylene oxide
polymerization is more environmentally benign, than
that of ILs.[25]
Results and Discussion
In the first stage of our research, various
poly(ethylene glycols) with different molecular
weights were tested, in a model hydroboration
reaction of phenylacetylene (2 a) with pinacolborane
(pinBH, 1) in the presence of Ru(CO)Cl(H)(PPh3)3
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800409
Advanced Synthesis & Catalysis
(1 mol%) to determine process feasibility and its
optimal conditions (Table 1).
Screening of the PEGs showed that the length of
their chains, as well as the type of end-groups, had a
crucial influence on the reaction yields.
Table 1. Optimization of ruthenium-catalyzed
hydroboration
of
phenylacetylene
(2a)
with
pinacolborane (1) in different types of PEGs.
The reaction with the uses of PEG 1-5, which
possess terminal hydroxyl groups did not lead to
product formation regardless of the molecular weight
of the PEGs, the reaction temperature and time
(Table 1, entries 1-6).
It can be explained by the competitive reaction of
pinacolborane with OH-ending groups in PEGs and
the simultaneous formation of aloxypinacolborane
and evolution of hydrogen, proved by the reaction of
ethylene glycol with pinacolborane in a sealed NMR
tube. This simple experiment proved that
hydroxylated PEGs are not suitable for hydroboration
reactions, as pinacolborane reacted rapidly with the
solvent.[29] The reaction performed in PEG 6-11
(containing OH groups blocked with SiMe3 or Me
groups) led smoothly to product 3 a with very high
yields at 100 °C for 3 hours, which was determined
temp.
[°C]
time
[h]
conv. of yield of
entry solvent
2aa) [%] 3ab) [%]
1
PEG 1
PEG 2
PEG 3
PEG 4
PEG 5
PEG 5
PEG 6
PEG 7
PEG 7
PEG 8
PEG 8
PEG 9
PEG 9
PEG 10
PEG 10
PEG 10
PEG 10
PEG 10
PEG 10
PEG 10
PEG 10
PEG 11
PEG 11
100
100
100
100
100
130
100
100
60
24
0
0
2
24
24
24
24
48
3
0
0
3
0
0
1
by the GC-MS and H NMR analyses (Table 1,
4
0
0
entries 7-8, 10, 12, 17, 22). The absence of the
reactive hydroxyl groups in the PEG 6-11 chain was
essential for the desired course of the reaction.
Almost exclusive formation of β-(E)-alkenyl
boronate was observed.
5
0
0
6
0
0
7
91
98
89
98
88
99
80
71
96
97
99
48
82
94
98
100
94
90
97
88
97
87
98
79
68
95
95
98
45
80
91
97
99
93
Our further studies were focused on determining
the effect of temperature on product yields and
selectivities. In a standard hydroboration procedure in
scCO2, 100 °C was used to obtain the total
conversion of reagents.[17] Lowering the reaction
temperature from 100 to 60 °C had a negative
influence on substrate conversion when the reaction
was carried out in PEG 6-9 and PEG 11.
Hydroboration of 2 a with 1 in PEG 10 at 60 °C for 3
hours resulted in almost complete substrate
conversion, as found at 100 °C. The selectivity of the
process was comparable at both temperatures for all
solvents. Reduction of the process time resulted in a
deterioration of product yields (Table 1, entries 18-
20).
Encouraged by these promising results for the
hydroboration of 2 a with 1 at 100 °C in PEG 6-11 as
well, as in PEG 10 at 60 °C, and their limited
miscibility with organic, nonpolar solvents we
decided to examine the recyclability of the developed
catalytic system (Figure 1).
To determine the reaction yield after each catalytic
cycle, products were extracted quantitatively with n-
hexane (3x5 mL). If the lower PEG phase-bearing
catalyst solidified, the upper hexane phase with
extracted products was easily decanted. Subsequently,
traces of the organic solvent were removed under
vacuum from the immobilized molecular complex
and the reactor was refilled with the next substrate
load.
8
3
9
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
100
60
3
3
100
60
3
3
100
100
100
100
60
0.5
1
2
3
0.5
1
60
60
2
60
3
100
60
3
3
It should be noted that the replacement of polar
hydroxyl groups with non-polar TMS groups at the
ends of appropriate PEGs significantly changed their
physicochemical properties. In all PEGs, with
Reaction conditions: [catalyst]:[2a]:[1]: = [0.01]:[1]:[1.2],
a)
0.55 g of PEG (approx. 0.5 M), argon. Determined by
b)
1
GC-MS analysis. Determined by H NMR and GC-MS
analyses.
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800409
Advanced Synthesis & Catalysis
Scheme 2. Scope of alkynes used in hydroboration
with 1 under optimized reaction conditions in PEG 10
Table 2. Hydroboration of terminal (2 a-g) and
internal alkynes (2 h-j) under optimized reaction
isolated
conv. of
selectivityb)
3/4/5 or 3/4
yield of
alkynea)
[%]
entry alkyne
3
[%]
Figure 1. Hydroboration of 2 a with 1 in the presence of
Ru(CO)Cl(H)(PPh3)3 (1 mol%) under repetitive batch
mode at 100 °C (PEG 6-10) and at 60 °C (PEG 10*).
1
2
3
2a
2b
2c
100
100
100
99/1/0
98/1/1
97/2/1
91
89
83
trimethylsilyl ending groups (PEG 6-10), lower
melting points, as well as better miscibility with non-
polar solvents, e.g. n-hexane, were observed.[30]
These phenomena were especially visible for PEGs
with lower molecular weights. PEG 6 was fully
miscible with n-hexane, n-heptane or n-octane, thus
isolation of the products without solvent and catalyst
leaching was not possible, even at low temperatures
(-20 – 4 °C). Therefore, only one catalytic cycle was
performed. Significantly better phase separation was
observed for PEG 7, although partial mutual
solubility of PEG 7 and n-hexane during product
extraction was also observed. Thus, a reduction of the
reaction yield was noticed in the 3rd run. For PEG 9
and PEG 10, with much higher average molecular
weights, excellent conversions and selectivities were
observed for 8 and 10 cycles. The reaction in PEG 11
with methyl ending groups, enabled us to obtain very
high yields of 3 a for 10 cycles. However, after the
5th run, a decrease in alkyne conversion was noticed.
The high molecular weight prevented the PEGs from
mixing with n-hexane, which was used for product
extraction. The hydroboration of 2 a with 1 in
PEG 10 was also very effective for up to 10 catalytic
cycles at 60 °C.
For all PEGs, yellow/orange homogeneous
reaction mixtures were observed throughout the
entire process. The extracts were analysed by ICP-
MS to determine catalyst leaching and the quality of
the TM-complex immobilization. In all these
experiments, the Ru content in the extracts was at
almost undetectable level (approximately 0.1 – 0.5
ppm). It proved that PEGs can be effectively used for
catalyst immobilization. The extraction method did
not affect metal leaching.[30]
90/5/5
(94/3/3)c)
83/7/10
4
5
2d
2e
77 (93)c)
57 (90)c)
78c)
66c)
(84/5/11)c)
6
7
2f
100
99
65/22/13
55
89
2g
95/2/3
46 (49)c)
93/7
8
9
2h
2i
(80)d)
71e)
60e)
79e)
(94/6)c), d), e)
(82)e)
72 (74)c)
(87)d)
83/17
(82/18)c)
(80/20) d), e)
(88)e)
72 (73)c)
(89)d)
96/4 (96/4)c)
(95/5) d), e)
10
2j
(91)e)
Reaction conditions: [catalyst]:[2]:[1]: = [0.01]:[1]:[1.2],
a)
60 °C, 3 h, 0.55 g of PEG 10 (approx. 0.5 M), argon.
b)
Determined by GC-MS analysis.
Determined by 1H
c)
d)
NMR and GC-MS analyzes. After 24 h. After 3 h at
100 °C. e) After 6 h at 100 °C.
For the optimized conditions, the hydroboration of
a wide scope of terminal (2 a-g) and internal alkynes
(2 h-j) with
1
was examined (Scheme 2).
Phenylacetylene and its derivatives (2 a-c) proceeded
almost quantitatively to β-(E)-alkenyl boronates (3 a-
c). Conversion and selectivity in hydroboration of
silylsubstituted alkynes (2 d-e) were lower in
comparison to phenylacetylenes but still at a
relatively high level. Extending the reaction time to
24 hours resulted in a significant improvement in
conversion without losing selectivity. Hydroboration
of 2 f and 2 g proceeded with full conversions.
However, poor selectivity was obtained if 2 f was
used as a reagent. Similar results were observed for
hydroboration of aliphatic alkynes performed in
Thus, the optimum reaction conditions involved
the use of Ru(CO)Cl(H)(PPh3)3 (1 mol%) in PEG 10
at 60 °C for 3 h in an argon atmosphere, in repetitive
cycles.
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800409
Advanced Synthesis & Catalysis
scCO2.[17] Additionally, the product 3 g was obtained
with a high selectivity due to steric hindrance of
alkyne 2 g (Table 2).
selectivities. All products were easily and
quantitatively extracted with n-hexane before the
next run (Figure 2).
The products obtained from each cycle were free
from reagents and products from the previous cycle,
showing the excellent efficiency of the developed
catalytic system.
The hydroboration of internal alkynes (2 h-j) with
1 was also carried out, under optimized reaction
conditions (Table 2, entries 8-10). In all cases, time
and temperature, previously determined for terminal
alkynes, was not sufficient to obtain a complete
conversion of the reagents. The reason for this is the
lower reactivity of internal alkynes and more shielded
triple C≡C bonds. Extension of the reaction time to
24 hours did not significantly improve conversion for
all alkynes. The process temperature had a greater
influence. Increasing the temperature from 60 °C to
100 °C resulted in better alkyne conversion in the
reaction carried out for 3 h. Doubling the reaction
time (to 6 h) had a weak influence on alkyne
conversions. Selectivities were comparable at both
temperatures. Conducting the process at a higher
temperature also had a positive effect on reaction
homogeneity.
If the hydroboration of 2 h and 2 i with 1 at 100 °C
was performed, dissolution of all the components was
observed, whereas at 60 °C the system was not fully
homogeneous.
In order to show the reusability, versatility and
utility of our catalytic system based on 1 mol% of
Ru(CO)Cl(H)(PPh3)3 in PEG 10, we carried out
subsequent hydroboration reactions of different
terminal alkynes within the same catalyst load
(Scheme 3). Hydroboration/extraction sequences of
2 a, 2 d, 2 f, 2 b, 2 c and again 2 a were performed
with excellent conversions and very good
Besides high activity, the applied synthetic
protocol is characterized by high tolerance to various
chemical functionalities presented in the alkyne
structures. Therefore, it can be considered as one of
the most efficient, universal and environmentally
benign tools for the hydroboration of alkynes.
Moreover, the high stability of the system based on
PEG 10, the absence of catalyst leaching, as well as
the simple and easy separation protocols,
(extraction/solvent evaporation) clearly affect the
process sustainability.
It is worth emphasizing that the obtained products,
due to the presence of reactive moieties (boryl, silyl,
bromo groups) and unsaturated double carbon-carbon
bonds (C=C), are valuable building blocks in organic
synthesis, and can be applied in further
transformations, e.g. Suzuki, Hiyama and Heck
couplings, deborylation or desilylation reactions. To
demonstrate this capability, we used crude n-hexane
extract, containing 3 a, in a Suzuki coupling with
bromobenzene (Scheme 4) (detailed procedure can be
found in the supporting information). The reaction
resulted in the complete conversion of 3 a and 94 %
isolation yield of (E)-1,2-diphenylethene.
Scheme 4. Suzuki coupling of 3 a (crude extract) with
bromobenzene.
Finally, we investigated whether increasing the
catalytic load would have an influence on the number
of repetitive batches, and if the gram-scale synthesis
of alkenyl boronates could be performed with the
previously discussed catalytic system.
To check whether the effect of catalyst loading on
the process efficiency was detectable for the
hydroboration of 2 a, the reaction was performed
with 2 mol% of Ru(CO)Cl(H)(PPh3)3 in PEG 10.
Doubling the catalyst content allowed 19 complete
Scheme 3. Reusability of the catalytic system
(Ru(CO)Cl(H)(PPh3)3/PEG 10 in hydroboration of
terminal alkynes.
Figure 2. Hydroboration/extraction sequences
performed in 1 mol% Ru(CO)Cl(H)(PPh3)3/PEG 10
catalytic system for series of terminal alkynes.
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800409
Advanced Synthesis & Catalysis
A system using a Ru(CO)Cl(H)(PPh3)3 catalyst in
PEGs with α-, ω-methyl or silyl ending groups, for
regio- and stereoselective hydroboration of a wide
range of alkynes in repetitive batches, was developed.
The system was found to be the most productive,
compared to previously described recyclable
hydroboration methods. PEG 10 with 2 mol% of Ru
catalyst gave the best results terms of efficiency and
recyclability in the reaction of pinacolborane (1) with
phenylacetylene (2a). It allowed the completion of 19
runs with the accumulative TON 1123, which clearly
indicates high system efficiency. Moreover, it was
possible to reduce the temperature of the process
from 100 °C to 60 °C in comparison to the previously
described reaction performed in scCO2. Almost
undetectable levels of leaching of the catalyst,
monitored by the ICP-MS, confirmed its good
immobilization in PEGs. The same catalyst load was
applied for the synthesis of a series of different
alkenyl boronates, one after another, in the
subsequent catalytic cycles. The effective
reaction/extraction procedure enabled pure products
to be obtained without contamination of the post-
reaction mixture with compounds from the previous
cycle. For terminal alkynes (E)-isomers were formed
in a significant amount at 60 oC in 3 h, while internal
alkynes yield (Z)-isomers in more extreme conditions
(100 oC, 6-24 h)
Finally, the gram-scale synthesis of (E)-4,4,5,5-
tetramethyl-2-styryl-1,3,2-dioxaborolane (3 a) was
carried out with a very high TON (3520). The partial
miscibility of the catalytic system and the reagents
used in gram amounts caused leaching of the catalyst
during the extraction. The proper concentration of
reagents, which could be achieved by the application
of continuous flow instead of repetitive batches,
would allow steady state reaction conditions to be
maintained. Nevertheless, the hydroboration system
based on PEGs fulfils the green chemistry
requirements, while the catalyst recyclability and
easy, low-cost reaction/separation method enables the
sustainability of the process.
Figure 3. Hydroboration of 2 a with 1 in PEG 10 in
the presence of a) 1 mol% and b) 2 mol% of
Ru(CO)Cl(H)(PPh3)3 at 60 °C in 3 hours.
catalytic runs to be carried out, after which a gradual
decrease in 3 a yield was observed. Accumulative
TON values were comparable for both catalyst loads
(1109 and 1123, respectively) (Figure 3).
To the best of our knowledge, the method
developed by us is the most efficient system for the
recyclable hydroboration of alkynes (according to the
protocols previously described in literature).
To check the possibility of carrying out gram-scale
synthesis, 2 a (10 mmol, 1.02 g) was reacted with 1
(12 mmol, 1.54 g) under optimized reaction
conditions to give 3 a, with 88 % yield. Despite the
fact that substrate concentrations were 40-times
higher compared to the milligram-scale level, we did
not observe a significant decrease in reaction
selectivity (96/2/2 vs 99/1/0; 3 a/4 a/5 a). However, a
very low catalyst load (0.025 mol%) was not
sufficient for the complete conversion of 2 a (conv.
92 %). It should be emphasized that a very high TON
(3520) was obtained. It should also be pointed out
that during the extraction process, partial mutual
miscibility of the catalyst-bearing PEG and the
product-rich n-hexane phase was evident, so simple
filtration through a syringe filter was needed.
Additionally, after some time, the precipitation of a
white solid (PEG 10 and catalyst) in the first and
second extract was observed. This phenomenon can
be explained through the partial dissolution of the
catalytic system in the relatively large product
volumes in the n-hexane phase, which affects its
solvent properties. In general, 16 % mass loss of the
catalytic system during extraction was observed.
Nevertheless, the applied methodology resulted in an
excellent TON value. Our actual research concerns
the possibility of utilizing the immobilization of Ru-
catalyst in PEG 10 in a continuous flow system. This
strategy will use the potential of the catalytic system
to eliminate mistakes derived from the reaction
during subsequent runs and to enable us to intensify
TON values using lower concentrations of reagents,
controlled by their flow rate and residence time in the
reactor.
Experimental Section
All manipulations were carried out in an argon atmosphere
using standard Schlenk’s line techniques.
Preparation of PEG 10
To a dry three-neck round bottom flask equipped with
stirring bar and reflux condenser, 10 mmol of PEG 5 was
added and dried under vacuum at 65 °C for over 16 hours.
Subsequently, 25 mmol of hexamethyldisilazane (HMDS)
at 65 °C was slowly added. The reaction was allowed to
continue until no further evidence of ammonia was
observed. Excess of HMDS was easily removed under
vacuum at 65 °C within 2 hours. After cooling to room
temperature, PEG 10 was solidified at 97 % yield and
1
characterized by FTIR and H, 13C NMR analyses, as well
as melting point measurement.
Conclusion
PEG 6-9 were prepared in the above-described procedure.
Hydroboration of alkynes in PEG 10
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800409
Advanced Synthesis & Catalysis
The PEG 10 (0.55 g) was placed into a Schlenk’s vessel
equipped with a stirring bar and dried under vacuum at
40 °C, for 16 hours. Subsequently, a catalyst (0.0025
mmol) was added to the reactor, evacuated for 1 hour and
refiled with argon. Next, alkyne (0.25 mmol) and 4,4,5,5-
tetramethyl-1,3,2-dioxaborolane (0.3 mmol) were added
and the reactions were performed at 60 °C for 3 hours for
terminal alkynes and at 100 °C for 6 hours for internal
alkynes. The molar concentration of the reagents was
approximately 0.5M. When the reactions were complete,
the products were extracted with dry n-hexane (3x5 mL).
The combined extracts were filtered (if necessary) and
isolated on silica gel using flash chromatography and
hexane/ethyl acetate (9:1) as the eluent. The purity of the
product was confirmed by 1H, 13C NMR and GC-MS
analysis.
[2] a) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457-
2483; b) A. J. Lennox, G. C. Lloyd-Jones, Chem. Soc.
Rev. 2014, 43, 412-443.
[3] E. Fernandez, K. Maeda, M. W. Hooper, J. M. Brown,
Chem. Eur. J. 2000, 6, 1840-1846.
[4]D. M. Chan, K. L. Monaco, R.-P. Wang, M. P. Winters,
Tetrahedron Lett., 1998, 39, 2933-2936.
[5] a) J. Szyling, A. Franczyk, P. Pawluć, B. Marciniec, J.
Walkowiak, Org. Biomol. Chem. 2017, 15, 3207-3215;
b) C. Morrill, R. H. Grubbs, J. Org.Chem. 2003, 68,
6031-6034.
[6] E. C. Neeve, S. J. Geier, I. A. Mkhalid, S. A. Westcott,
Hydroboration of alkynes in PEG 10 in repetitive batches
T. B. Marder, Chem. Rev., 2016, 116, 9091-9161.
PEG 10 (0.55 g) was placed into a Schlenk’s vessel
equipped with a stirring bar and dried under vacuum at
40 °C, for over 16 hours. Subsequently, a catalyst (0.0025
mmol) was added and evacuated for 1 hour and refiled
with argon. Next, the alkyne (0.25 mmol) and 4,4,5,5-
tetramethyl-1,3,2-dioxaborolane (0.3 mmol) were added
and the reactions were carried out at 60 °C. The molar
concentration of reagents was approximately 0.5M. After 3
hours the products were extracted with dry n-hexane
(3x5 mL). The combined extracts were filtered (if
necessary) and analyzed by GC-MS and 1H analyses.
Subsequently, the traces of n-hexane were removed under
vacuum. A new substrate load was added, and the process
was repeated in the above-described conditions.
[7] a) J. Pyziak, J. Walkowiak, M. Hoffmann, B.
Marciniec, J. Organomet. Chem. 2015, 794, 96-103; b)
J. Walkowiak, M. Jankowska‐Wajda, B. Marciniec,
Chem. Eur. J., 2008, 14, 6679-6686.
[8]C. Morrill, T. W. Funk, R. H. Grubbs, Tetrahedron Lett.
2004, 45, 7733-7736.
[9] a) B. Marciniec, M. Jankowska, C. Pietraszuk, Chem.
Commun. 2005, 663-665; b) J. Walkowiak, B.
Marciniec, M. Jankowska–Wajda, J. Organomet. Chem.
2010, 695, 1287-1292.
[10] a) I. Beletskaya, C. Moberg, Chem. Rev. 2006, 106,
2320-2354; b) I. Beletskaya, A. Pelter, Tetrahedron,
1997, 53, 4957-5026; c) B. M. Trost, Z. T. Ball,
Synthesis, 2005, 2005, 853-887; d) M. Zaidlewicz, A.
Wolan, M. Budny, in Comprehensive Organic
Synthesis II (Second Edition), (Eds.: Knochel and
Molander), Elsevier, Amsterdam, 2014, pp. 878-955.
Gram-scale hydroboration in PEG 10
A catalytic system (PEG10/catalyst) was prepared in same
manner as described for hydroboration of alkynes in PEG
10. Subsequently, the alkyne (10 mmol, 1.02 g) and
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (12 mmol, 1.54 g)
were added and the reactions were carried out at 60 °C for
3 hours. When reaction was complete, the products were
extracted quantitatively with the n-hexane (7x5 mL).
Previously filtered extracts were combined, evaporated
under vacuum and isolated on silica gel using flash
chromatography and hexane/ethyl acetate (9: 1) as the
eluent to give 2.01 g of 3 a (88%).
[11] a) B. Sundararaju, A. Fürstner, Angew. Chem. 2013,
125, 14300-14304; b) S. Pereira, M. Srebnik,
Organometallics, 1995, 14, 3127-3128; c) B. H.
Lipshutz, Ž. V. Bošković, D. H. Aue, Angew. Chem.,
2008, 120, 10337-10340; d) J.-E. Lee, J. Kwon, J. Yun,
Chem. Commun. 2008, 733-734; e) C. Gunanathan, M.
Hꢀlscher, F. Pan, W. Leitner, J. Am. Chem. Soc. 2012,
134, 14349-14352; f) H. R. Kim, I. G. Jung, K. Yoo, K.
Jang, E. S. Lee, J. Yun, S. U. Son, Chem. Commun.
2010, 758-760; g) R. Alfaro, A. Parra, J. Alemꢁn, J. L.
Garcꢂa Ruano, M. Tortosa, J. Am. Chem. Soc. 2012,
134, 15165-15168; h) C.-C. Tai, M.-S. Yu, Y.-L. Chen,
W.-H. Chuang, T.-H. Lin, G. P. Yap, T.-G. Ong, Chem.
Commun. 2014, 4344-4346; i) Y. D. Bidal, F. Lazreg
and C. S. Cazin, ACS Catal. 2014, 4, 1564-1569; j) A.
L. Moure, R. Gomez Arrayas, D. J. Cꢁrdenas, I. s.
Alonso, J. C. Carretero, J. Am. Chem. Soc. 2012, 134,
7219-7222.
Acknowledgements
The authors acknowledge the financial support from the National
Centre for Research and Development in Poland – Lider
Programme No. LIDER/26/527/L-5/13/NCBR/2014 and National
Science Centre (Poland)
2014/15/B/ST5/04257
–
Project Opus, No. UMO-
References
[1] a) D. S. Matteson, Stereodirected synthesis with
organoboranes, Springer, Berlin, 1995, pp 48-158; b)
A. Pelter, K. Smith, H. C. Brown, Borane reagents,
Academic Press, London, 1988; c) C. M. Vogels and S.
A. Westcott, Curr. Org. Chem. 2005, 9, 687-699; d) K.
Burgess, M. J. Ohlmeyer, Chem. Rev. 1991, 91, 1179-
1191; e) R. Barbeyron, E. Benedetti, J. Cossy, J.-J.
Vasseur, S. Arseniyadis, M. Smietana, Tetrahedron,
2014, 70, 8431-8452; f) D. G. Hall, Boronic acids:
preparation, applications in organic synthesis and
medicine, John Wiley & Sons, 2012.
[12] a) D. J. Cole-Hamilton, R. P. Tooze, Catalyst
separation, recovery and recycling: chemistry and
process design, Springer Science & Business Media,
2006; b) D. J. Cole-Hamilton, Science, 2003, 299,
1702-1706.
[13] a) V. S. Rawat, B. Sreedhar, Synlett 2014, 25, 1132-
1136; b) B. Mohan, K. H. Park, Appl. Catal., A 2016,
519, 78-84; c) A. Khan, A. M. Asiri, S. A. Kosa, H.
Garcia, A. Grirrane, J. Catal. 2015, 329, 401-412.
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800409
Advanced Synthesis & Catalysis
[14] Z.-J. Yao, S. Hong, W. Zhang, M. Liu, W. Deng,
Tetrahedron Lett. 2016, 57, 910-913.
[24] a) C. B. Smith, C. L. Raston, A. N. Sobolev, Green
Chem. 2005, 7, 650-654; b) A. R. Tiwari, B. M.
Bhanage, Green Chem. 2016, 18, 144-149; c) K. S. Feu,
F. Alexander, S. Silva, M. A. de Moraes Junior, A. G.
Corrêa, M. W. Paixão, Green Chem. 2014, 16, 3169-
3174; d) S. Chandrasekhar, C. Narsihmulu, S. S.
Sultana, N. R. Reddy, Org. Lett. 2002, 4, 4399-4401;
e) R. A. Sheldon, Green Chem. 2005, 7, 267-278; f) J.
Chen, S. K. Spear, J. G. Huddleston, R. D. Rogers,
Green Chem. 2005, 7, 64-82.
[15] J. J. Juliette, D. Rutherford, I. T. Horváth, J. Gladysz,
J. Am. Chem. Soc. 1999, 121, 2696-2704.
[16] S. Aubin, F. Le Floch, D. Carrie, J. Guegan, M.
Vaultier, in Ionic Liquids: Industrial Applications for
Green Chemistry, (Eds: Rogers and Seddon) ACS
Publications, 2002, 334-346.
[17]. J. Szyling, A. Franczyk, K. Stefanowska, M. Klarek,
H. Maciejewski, J. Walkowiak, ChemCatChem 2018,
10, 531-539.
[25] P. G. Jessop, Green Chem. 2011, 13, 1391-1398.
[26] S. K. Singh, P. S. Murthy, G. C. Joshi, Tetrahedron
Lett. 1992, 33, 2419-2420.
[18] A recent comparison of prices of PEGs and ionic
liquids (which have the similar solvent properties)
reveals that the first one are usually a few to even ten
times cheaper (Sigma-Aldrich webpage).
[27] M. Solinas, J. Jiang, O. Stelzer, W. Leitner, Angew.
Chem. Int. Ed. 2005, 44, 2291-2295.
[28] a) J. Walkowiak, B. Marciniec, Organometallics,
2012, 31, 3851-3856; b) J. Szyling, J. Walkowiak,
Green Proc. Synth., 2017, 6, 301-310; c) K.
Stefanowska, A. Franczyk, J. Szyling, K. Salamon, B.
Marciniec, J. Walkowiak, J. Catal. 2017, 356, 206-
213; d) J. Walkowiak, G. Franciò, W. Leitner, in
Applied Homogeneous Catalysis with Organometallic
Compounds: A Comprehensive Handbook in Four
[19] a) C. Fruijtier-Pölloth, Toxicology 2005, 214, 1-38;
b) F. J. Bailey, Poly(ethylene oxide), Academic Press,
1976; c) D. J. Heldebrant, P. G. Jessop, J. Am. Chem.
Soc. 2003, 125, 5600-5601; d) K. Knop, R.
Hoogenboom, D. Fischer, U. S. Schubert, Angew.
Chem. Int. Ed. 2010, 49, 6288-6308; e) J. M. Harris,
Poly (ethylene glycol) chemistry: biotechnical and
biomedical applications, Springer Science & Business
Media, 2013.
Volumes, Third Edition, John Wiley
& Sons,
Weinheim, Germany, 2018, pp. 1221-1258; e) P.
Pawluć, A. Franczyk, J. Walkowiak, G. Hreczycho, M.
Kubicki, B. Marciniec, Org. Lett. 2011, 13, 1976-1979;
f) J. Pyziak, J. Walkowiak, B. Marciniec, Chem. Eur. J.
2017, 23, 3502-3541.; g) A. Franczyk, K. Stefanowska,
M. Dutkiewicz, D. Frąckowiak, B. Marciniec, Dalton
Trans. 2017, 46, 158-164.
[20] a) R. Liu, H. Cheng, Q. Wang, C. Wu, J. Ming, C. Xi,
Y. Yu, S. Cai, F. Zhao, M. Arai, Green Chem. 2008, 10,
1082-1086; b) F. Harraz, S. El-Hout, H. Killa, I.
Ibrahim, J. Catal. 2012, 286, 184-192; c) U. R. Pillai,
E. Sahle-Demessie, J. Mol. Catal. A: Chem. 2004, 222,
153-158; d) S. Chandrasekhar, T. Shyamsunder, G.
Chandrashekar, C. Narsihmulu, Synlett, 2004, 2004,
522-524.
[29] To check the reactivity of the pinacolborane with
PEG, a reaction of 2eq. of pinacolborane with ethylene
glycol (1eq) was carried out in CDCl3 in sealed NMR-
tube. The reaction was monitored by NMR
spectroscopy. The evolution of molecular hydrogen at
[21] M. Vafaeezadeh, M. M. Hashemi, J. Mol. Liq. 2015,
207, 73-79.
[22] C. Xu, Z.-Q. Wang, W.-J. Fu, X.-H. Lou, Y.-F. Li,
F.-F. Cen, H.-J. Ma, B.-M. Ji, Organometallics, 2009,
28, 1909-1916.
1
4.52 ppm in H NMR spectrum was observed (see
supporting information).
[30] See supporting inforamtion.
[23] a) M. Ding, X. Jiang, J. Peng, L. Zhang, Z. Cheng, X.
Zhu, Green Chem. 2015, 17, 271-278; b) Z. Hu, X.
Shen, H. Qiu, G. Lai, J. Wu, W. Li, Eur. Polym. J.
2009, 45, 2313-2318.
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800409
Advanced Synthesis & Catalysis
FULL PAPER
A recyclable Ru(CO)Cl(H)(PPh3)3/PEG catalytic system
for regio- and stereoselective hydroboration of terminal
and internal alkynes
Adv. Synth. Catal. Year, Volume, Page – Page
Jakub Szyling, Adrian Franczyk, Kinga
Stefanowska and Jędrzej Walkowiak*
9
This article is protected by copyright. All rights reserved.