In Water Markovnikov Hydration and One-Pot Reductive Hydroamination of Terminal Alkynes under Ruthenium Nanoparticle Catalysis

Article abstract of DOI:10.1002/ejic.201901235

In the presence of Shvo's catalyst [2,3,4,5-tetraphenyl-1,3-cyclopentadien-1-ol, ruthenium(II) complex], a small quantity of aniline and TGPS-750-M surfactant, terminal alkynes were hydrated under microwave (MW) dielectric heating in water as solvent with high conversion and good yield. The reaction gives the Markovnikov product exclusively, unlike that commonly observed with ruthenium complexes. Under the influence of MWs, Ru nanoparticles embedded in the nanomicelle environment were formed, acting as the effective hydration catalyst. Introducing sodium formate in the aqueous phase and using a stoichiometric amount of amines, the Ru nanoparticle nanomicelle catalyst gave the first example of one-pot single-step hydroamination of alkynes with the formation of the corresponding secondary amines. The reaction is characterized by low environmental impact as TGPS-750-M is required in low amount, and organic solvents employed only for product separation or catalyst recycling.

Full text of DOI:10.1002/ejic.201901235

A Journal of
Accepted Article
Title: In water Markovnikov hydration and one-pot reductive
hydroamination of terminal alkynes under Ruthenium
nanoparticle catalysis
Authors: Caterina Risi, Elena Cini, Elena Petricci, Simone Saponaro,
and Maurizio Taddei
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To be cited as: Eur. J. Inorg. Chem. 10.1002/ejic.201901235
Link to VoR: http://dx.doi.org/10.1002/ejic.201901235

10.1002/ejic.201901235
European Journal of Inorganic Chemistry
COMMUNICATION
In water Markovnikov hydration and one-pot reductive
hydroamination of terminal alkynes under Ruthenium
nanoparticle catalysis
Caterina Risi,[a] Elena Cini,[a] Elena Petricci,[a] Simone Saponaro,[a] and Maurizio Taddei*[a][b]
Abstract: In the presence of Shvo’s catalyst (2,3,4,5-tetraphenyl-1,3-
cyclopentadien-1-ol, ruthenium(II) complex), a small quantity of
aniline and TGPS-750-M surfactant, terminal alkynes were hydrated
under microwave (MW) dielectric heating in water as solvent with high
conversion and good yield. The reaction gives the Markovnikov
product exclusively, unlike that commonly observed with ruthenium
complexes. Under the influence of MWs, Ru nanoparticles embedded
in the nanomicelle environment were formed, acting as the active
hydration catalyst. Introducing sodium formate in the aqueous phase
and using a stoichiometric amount of amines, the Ru nanoparticle
nanomicelle catalyst gave the first example of one-pot single-step
hydroamination of alkynes with the formation of the corresponding
secondary amines. The reaction is characterized by low
environmental impact as TGPS-750-M is required in low amount, and
organic solvents employed only for product separation or catalyst
recycling.
14], and even metal-free conditions based on strong protic acids
have been described.[15,16] As hydration, water is necessary for
the reaction, but the low solubility of the substrates and the
catalysts in water often requires the presence of large amounts of
a co-solvent as MeOH, EtOH, acetone, dioxane, DCM, toluene or
acetonitrile.
The use of surfactants appears as a promising alternative to
overcome the concerns relative to the use of dangerous solvent
for organic transformation.[17] Micelles formed by surfactants in
water may solubilize organic molecules and organometallic
catalysts, forming a nanosized environment that may accelerate
the reaction rate.[18–20]
Results and Discussion
Following our interest in organic transformations mediated by Ru-
based catalysts,[21–24] we became interested in studying the
alkyne hydration in a water/micelle environment. Examples of
classic Ru catalyzed anti-Markovnikov hydration in the presence
of SDS has been described[25] and few other examples of
Markovnikov type hydration with different Pt, Au[26–28] and Ag[29]
lipophilic complexes in the presence of surfactants have been
described.
Introduction
The formation of carbonyl compounds through hydration of
alkynes is an atom economical and efficient process largely
employed by synthetic chemists.[1] Since the original Kucherov’s
discovery based on toxic mercury salts in aqueous sulfuric acid,[2]
The hydration of phenylacetylene was selected as the model
reaction (Table 1). To find the best combination of surfactant and
catalyst, we explored different Ru catalysts looking to the best
conversion of the starting material into the Markovnikov
(acetophenone, 2a) or anti-Markovnikov (phenylacetaldehyde,
2b) products. We opted for surfactant TPGS-750-M (Table 1),
developed for successful applications in metal-catalyzed
reactions,[30] to screen different Ru based catalysts. Unfortunately,
all the Ru catalysts employed, independently from Ru oxidation
levels or the presence of ligands, gave disappointing results, even
after microwave dielectric heating up to 150 °C (entries 1-10 in
Table 1). Only using RuCl3, phenylacetylene was consumed with
the formation of a mixture of hydration compounds[31] 2a and 2b
together with (1-methyl-2-phenyl-cyclopropyl)benzene (3)
obtained probably through dimerization of the Ru(II) acetylene (or
vinylidene) complex[32] (entries 1, 2 in Table 1).
The use of Brønsted acid and base catalysts may improve the
alkyne hydration, so we investigated the addition of different
catalytic acids and bases to the Ru catalyzed hydration in the
micellar environment. We were pleased to see that 5% molar of
aniline provides the almost quantitative conversion of
phenylacetylene into acetophenone (Markovnikov orientation) in
the presence of the Shvo’s catalyst (entry 11 in Table 1).
a
large number of hydration conditions are based on
organometallic catalysis. A proper choice of the metal and the
potential ligands may drive the reaction towards the Markovnikov
or the anti-Markovnikov product. Amongst transition metal, first
row elements show low reactivity in hydration, while Rh, Pd, Pt,[3]
Au,[4–6] Ir and Ag, often gives the Markownikov product in good
yields.[1][7] On the other hand, the anti-Markovnikov water addition
is a prerogative of Ru based catalysts such as [CpRu(PR3)2]X
supported by phosphine ligands as dppe, PMe3, PMePh2,
PMe2Ph and dppb.[1][8] Other Ru based catalysts work properly,
giving the aldehyde product when applied to terminal alkynes.[9][10]
Different metal triflates have also been employed as catalysts[11–
[a]
C. Risi, Dr. E. Cini, Prof. Dr. E. Petricci, S. Saponaro, Prof. M.
Taddei
Dipartimento di Biotecnologie, Chimica e Farmacia
Università degli Studi di Siena
Via A. Moro 2, 53 100, Siena Italy
E-mail: maurizio.taddei@unisi.it
[b]
Prof. M. Taddei
CNR - ICCOM Istituto di Chimica dei Composti Organometallici
Via Madonna del Piano 10, 50019 Sesto Fiorentino (FI) - Italy
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/ejic.201901235
European Journal of Inorganic Chemistry
COMMUNICATION
The mixture was heated under MW dielectric heating at 100 °C
for 60 min (6 cycles of 10 min each). The reaction was carried out
mixing phenylacetylene (1 eq) the catalysts (1% mol) and aniline
(5 % mol) in water containing NaCl (1% mol) and the surfactant
TPGS-750-M (2.5% wt). In the end, a black organic phase was
formed on the water surface and separated with a small amount
of EtOAc. After passage on a short path of silica and solvent
evaporation, acetophenone was isolated in 85% yield. To
investigate the catalyst nature, we analyzed the composition of
the organic phase after the extraction. The 1HNMR spectrum after
solvent evaporation clearly showed that during the reaction, the
Shvo’s catalyst changed, while TEM analysis highlighted the
formation of Ru nanoparticles embedded into the micellar
environment (see SI).
This type of nanoparticles already forms mixing Shvo’s catalyst
and aniline in water/TGPS-750-M and heating at 100 °C for 30
min. After addition of phenylacetylene and further MW heating at
the same temperature for 60 min, hydration occurred, and
phenylacetylene was isolated in high yield. The formation of Ru
nanoparticles may also explain why hydration gives the
Markownikov product exclusively, while other Ru (II) catalyzed
hydration in the presence of sodium dodecyl sulphate (SDS) have
been reported to give the anti-Markownikov orientation product.[25]
When SDS was used as surfactant together with Shvo’s catalyst
and aniline in water and the mixture heated to 100 °C under MWs,
nanoparticles start to form. The further addition of
phenylacetylene gave again exclusively acetophenone (80 %
conversion), demonstrating that the reaction is independent of the
surfactant nature but only reliant on the catalyst nature. The best
previously found reaction conditions were applied to different
alkynes to explore the reaction scope as reported in Scheme 1.
Differently substituted aryl acetylenes always gave good
conversions while aliphatic and internal alkynes did not undergo
hydration.
Table 1. Exploration of the best reaction conditions for the Ru catalysed alkyne
hydration.
En.
Catalyst
Reaction
conditions[a]
Product[b]
1 (7%), 2a/2b
(38%), 3 (40%)
1
2
RuCl3.H2O
RuCl3.H2O
100 °C, 60 min
PPh3, 100 °C,
60 min
1 (13%), 2a/2b
(50%), 3 (35%)
3
4
5
Ru(acac)3
110°C, 120 min
100 °C, 60 min
150 °C, 60 min
sm[c]
sm
(Ph3P)3Ru(CO)(Cl)H
(Ph3P)3Ru(CO)(Cl)H
sm
XPhos (3%),
100 °C, 60 min
6
(Ph3P)3Ru(CO)(Cl)H
sm
7
8
[ClCp*Ru]4
100 °C, 60 min
100 °C, 60 min
sm
sm
[Ru(COD)Cl2]n
sm + by-
products
9
Shvo’s catalyst
Shvo’s catalyst
Shvo’s catalyst
Shvo’s catalyst
Ru(acac)3
100 °C, 60 min
XPhos[d] (3%),
100 °C, 60 min
sm + by-
products
10
11
12
13
14
15
Aniline (5%),
100 °C, 60 min
2a (95%)
2a (93%)
sm
Aniline (5%),
120 °C, 8 h[e]
Aniline (5%),
100 °C, 60 min
Aniline (5%),
100 °C, 60 min
(Ph3P)3Ru(CO)(Cl)H
[ClCp*Ru]4
sm
Aniline (5%),
100 °C, 60 min
sm
[a] Alkyne (0.5 mmol), TGPS-750-M (2.5% wt) NaCl (1 % mol) Ru catalyst (1%
mol), water (1 mL), MW dielectric heating. [b] Conversions determined by
GC/MS of the crude obtained by extraction with AcOEt as reported in SI. [c]
Starting materials [d] 2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl
[e] Convectional heating in oil bath.
Scheme 1. Hydration of different terminal alkynes. Yields of isolated products
(see SI).
Hydration occurred exclusively when Shvo’s catalyst was
employed, while with other Ru based catalysts the addition of 5%
aniline did not work (entries 13-15). The reaction also occurred
under convectional heating at 120 °C for 8 h in a sealed tube
immersed in an oil bath (entry 12).
This was a surprising result as the Shvo’s catalyst has been
employed mainly in alkyne hydrogenation or other red-ox
transformations on ketones, alcohols or amines.[33]
The potential formation of Ru nanoparticles embedded in the
surfactant environment suggested us the possibility to try a one-
pot reductive hydroamination of alkynes. A primary amine present
in solution might intercept the intermediate ketones obtained by
Ru catalyzed hydration, and the imine formed reduced by the
same Ru catalyst in the presence of a hydrogen donor. Several
examples of alkyne hydroamination catalyzed by transition metal
catalysts have been described to give the corresponding imine or
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10.1002/ejic.201901235
European Journal of Inorganic Chemistry
COMMUNICATION
enamine,[34–37] while few hydroamination procedures for the one-
pot transformation of alkynes into secondary amine are
known.[38,39]
Scheme 3. Scope of the reductive amination of phenylacetylene. Yields of
isolated products (see SI).
Catalyst recycle
86
84
82
80
78
76
74
72
70
Scheme 2. One-pot single step reductive amination of phenylacetylene.
The reductive amination of acetophenone was firstly investigated
on the crude separated after Ru-catalyzed hydration of
phenylacetylene. After separation from the aqueous phase,
compound 2a, mixed with the Ru nanoparticles embedded in the
surfactant, was added to a solution of HCOONa (10 eq)
containing 1.5 eq of aniline and submitted to MW dielectric
heating at 100°C for 60 min. GC/MS analysis of the crude showed
65% conversion into (1-phenylethyl)aniline (10). Then the
reaction was repeated mixing phenylacetylene, Shvo’s catalyst,
TGPS-750-M, aniline, water, NaCl and HCOONa and heating to
100°C for 60 min under MWs. GC/MS analysis of the crude
showed 61% conversion into aniline 10. Different formates were
employed as hydrogen donor, and different conditions attempted,
finding that conversion was increased using aqueous HCOONH4
(5 eq) in the presence of 2.5% molar of the surfactant and 1% mol
of the catalyst. The addition of catalytic amounts of acids (as p-
TSA or benzoic acid) gave a further increase of yields. The
catalyst could be assembled also in-situ mixing a 1:3 ratio of
Ru3(CO)12 and tetraphenylcyclopentadienone in H2O/TPGS-750-
M (2.5 %), NaCl (1%), followed by MW dielectric heating at 100 °C
for 60 min. Then phenylacetylene, aniline, ammonium formate
and benzoic acid were added, and the mixture heated at 100°C
(MWs, 6 cycles of 10 min) giving 85% conversion into 10. The
reaction worked well with other different substituted anilines as
reported in Scheme 3.
1
2
3
4
Conversion (%)
Figure 1. Recycle of the catalyst
The residue was then dispersed in water and recycled up to 4
times without any significant decrease in the product yield (Figure
1).
Conclusions
In conclusion, we have developed a new catalyst based on Ru
nanoparticles suitable for hydration of alkynes in water containing
2.5% of TPGS-750-M surfactant. The same micellar nanocatalytic
system gave rise to the first example of one-pot single step
reductive hydroamination of alkynes in water. The process
produces ketones and secondary amines with low environmental
impact as surfactant is required in low quantity, and the use of
organic solvents is limited to product separation and catalyst
recycling. The application of this MW assisted Ru nanoparticle-
nanomicelle catalysis to other organic transformations is currently
underway.
The catalyst, together with the surfactant, stays in the organic
phase in this case, too. Consequently, the Ru nanoparticle-
nanomicelle catalytic system could be separated from the product
diluting with EtOAc, extracting with aqueous HCl and evaporating
the organic solvent after drying.
Acknowledgments
This work was financially supported by the project “Development
and application of QM/MM technologies for the design of light
responsive proteins or protein-mimics based on rhodopsin
architecture” within the program “Dipartimenti di Eccellenza -
2018–2022 financed by MIUR (Rome, Italy).
Keywords: nanoparticles • microwave chemistry •
hydroamination • Ruthenium • green chemistry
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This article is protected by copyright. All rights reserved.