Ruthenium catalyzed regioselective coupling of terminal alkynes, amine and carbon dioxide leading to anti-Markovnikov adducts

Article abstract of DOI:10.1039/c4ra03836c

RuCl₂(p-cymene)/DPPE catalyzed addition of secondary amines and CO₂ to terminal alkynes affording anti-Markovnikov adducts of vinyl carbamates in good yield with excellent regioselectivity is reported. The catalyst, consisting of lab

Full text of DOI:10.1039/c4ra03836c

RSC Advances
View Article Online
View Journal | View Issue
COMMUNICATION
Ruthenium catalyzed regioselective coupling of
terminal alkynes, amine and carbon dioxide leading
to anti-Markovnikov adducts†
Cite this: RSC Adv., 2014, 4, 23022
Received 26th April 2014
Accepted 14th May 2014
*
Rahul A. Watile and Bhalchandra M. Bhanage
DOI: 10.1039/c4ra03836c
www.rsc.org/advances
RuCl2(p-cymene)/DPPE catalyzed addition of secondary amines and replace these toxic reagents by catalytic incorporation of CO2
CO2 to terminal alkynes affording anti-Markovnikov adducts of vinyl into organic substrate for their functionalization.8a–c
carbamates in good yield with excellent regioselectivity is reported.
Few groups have reported ruthenium based catalytic proto-
The catalyst, consisting of labile p-cymene displays very high regio- cols for the synthesis of vinyl carbamates using carbon
selectivity towards the anti-Markovnikov adducts and was applicable dioxide as C1 source like RuCl2(norbornadiene)(pyridine)2,
to a variety of aliphatic/aromatic alkynes and secondary amines.
[RuCl2(norbornadiene)]n, Ru3(CO)12, RuCl3 : 3H2O,9a,b bis-(h5-
cyclooctadienyl)ruthenium, Ru-(COD)(COT)-tertiary phosphine
and [RuCl2(C5H5N)4], [RuCl2(6-C6H6)(PMe3)].10a,b Despite of
their potential utility, the above methods suffer from one or
more drawbacks like lower yield and poor regioselectivity,
requirement of expensive, air sensitive and toxic ligands which
limits their application. Also, generality of the protocol has not
been explored with respect to the structural and electronic
variation of alkynes as well as amines. Therefore, there is a need
to develop an active, stable, regioselective catalyst for the one
pot synthesis of vinyl carbamates from carbon dioxide, amines
and alkynes which could be worked efficiently under mild
reaction condition, is a subject of the present work.‡
Low-valent ruthenium complexes have proven to be
excellent catalysts for this transformation. The features of
[RuCl2(p-cymene)]2, complex to spontaneously form a Ru-
vinylidene in the presence of a terminal alkyne were tempted
us to develop a system able to catalyze vinyl carbamates
synthesis using carbon dioxide, secondary amines and
alkynes.11a–c
In recent years, the use of carbon dioxide (CO2) for the
production of industrially important intermediates has attrac-
ted much more attention under the current background of the
increase of emissions of CO2.1,2 However, the activation of CO2,
a very stable molecule, is one of the biggest challenges in
chemistry. Transition metal catalyzed transformation of CO2
into vinyl carbamates, or enol carbamates is one of the attrac-
tive routes in CO2 chemistry. Vinyl carbamates or enol carba-
mates are important building blocks, possessing wide
application in agrochemicals, pharmaceuticals and are also
essential monomers for transparent polymers and varnishes.3a,b
There are several synthetic pathways described for the
preparation of vinyl carbamates in the literature (Scheme 1).
Conventionally, alkyl carbamates synthesized via reaction of an
amines with chloroformates,4a,b the dehydrohalogenation of
a-halogeno,5a,b b-halogenoalkyl carbamates6 and addition of
amines to vinyl chloroformates (VOC-Cl).7a,b A reaction of VOC-
Cl with an amine is mostly used for the preparation of vinyl
carbamates (Scheme 1).7b These traditional synthetic methods
are associated with several limitations including use of
poisonous carbonyl source, use of toxic and difficult to handle
intermediates, multiple reaction steps, low atom efficiency with
a stoichiometric use of reagents which result in the formation of
chemical waste. There are several efforts have been made to
Department of Chemistry, Institute of Chemical Technology, Matunga, Mumbai, 400
019, India. E-mail: bm.bhanage@gmail.com; bm.bhanage@ictmumbai.edu.in; Fax:
+91 22 3361 1020; Tel: +91 22 3361 1111/2222
† Electronic supplementary information (ESI) available: Experimental,
characterization data of catalyst. See DOI: 10.1039/c4ra03836c
Scheme 1 Traditional synthesis of vinyl carbamates.
23022 | RSC Adv., 2014, 4, 23022–23026
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
RuCl3–EDTA was found to be ineffective (Table 1, entry 5). Next
we screened RuCl2(p-cymene) as a catalyst which furnished 62%
conversion of desired Z-isomer of the product. This increase in
yield by using RuCl2(p-cymene) precursor encouraged us to
engage different phosphine ligands. Various phosphine con-
taining ligands were screened for addition reactions of
secondary amine and CO2 to terminal alkynes. The best result
was obtained by using DPPE as a ligand [DPPE ¼ 1,1-bis(di-
phenylphosphino)ethane] (78%), while other ligands were
found to give moderate yield of desired product (Table 1, entries
7 and 9). The RuCl2(p-cymene)/DPPE (1 : 1 ratio) was found to
be the best catalyst providing good yield (78%) of vinyl carba-
mate with an excellent Z/E ratio of 93 : 07 (Table 1, entry 8). The
reactivity trend could results from the fact that there exist a
labile p-cymene which could have displayed a very high regio-
selectivity towards the anti-Markovnikov adducts of alkenyl
carbamates.
In transition metal-catalyzed reactions, the amount of
catalyst employed proves to be an important aspect, consid-
ering this, the efforts were made to determine the optimum
loading of the catalyst. We studied the catalyst loading ranging
from 0.3 to 1.5 mol%, where increase in initial catalyst
concentration up to 1.0 mol% has increased the yield of desired
product (Table 1, entries 10–12) while further increase in the
amount of catalyst had no profound effect on the yield of the
desired product as well as selectivity (Table 1, entry 12).
The effect of different solvents on the reaction system was
investigated and it was observed that nature of solvent affected
the conversion of the reaction (Table 2, entries 1–7). The
solvents like toluene, N,N-dimethylformamide (DMF), tetra-
hydrofuran (THF), 1,4-dioxane and acetonitrile (ACN) were
screened for the standard reaction. However, among all the
solvents screened ACN was found to furnish good yield and
regioselectivity (Table 2, entry 4).
Scheme 2 Ru-catalyzed synthesis of vinyl carbamate from CO2.
Continuing our efforts towards the development of a new
facile protocol for incorporation of CO2 into organic chem-
icals,12 here, we employed the RuCl2(p-cymene)/DPPE as an
efficient and highly active catalyst for regioselective synthesis of
vinyl carbamates using carbon dioxide, secondary amines and
alkynes (Scheme 2).
In order to optimize the reaction conditions, initially the
reactions of secondary amine and CO2 to terminal alkynes were
chosen as the model reaction. Various reaction parameters such
as catalyst screening, catalyst loading, effects of solvents, and
effect of CO2 pressure, reaction temperature and time were
investigated and the results obtained are summarized in Table 1
and 2.
Firstly, we screened various metal complexes such as RuCl2/
(TPPTS)3, RuCl2/(TPPTS)3/SILPC and b-diketonate complexes
like Ru(acac)3, [Ru(TMHD)3]12a and RuCl3–EDTA (Table 1,
entries 1–5). It was observed that the complexes like RuCl2/
(TPPTS)3, RuCl2/(TPPTS)3/SILPC gave lower conversion of
desired product (up to 30%). Whereas, b-diketonate complexes
gave 17% yield. The complexes involving N-containing ligand,
Table 1 Effect of catalyst on vinyl carbamate synthesis from phenyl
a
acetylene, diethyl amine and CO2
To examine the effect of reaction temperature on the yield of
vinyl carbamates synthesis, the catalytic reaction of phenyl-
acetylene, diethylamine and CO2 were studied at different
reaction temperature ranging from 60–100 ꢀC (Table 2, entries 8
and 9). It was observed that at 60 ꢀC the yield of the desired
Selectivity product was low whereas with increase in reaction temperature
Entry
Catalyst (loading mol%)
Yieldb (%)
(2a : 2b)
up to 80 ꢀC, the yield and selectivity of vinyl carbamate towards
the Z-isomer (2a) was found to increase in 24 h. Further increase
in the temperature to 100 ꢀC resulted in decreased yield and
selectivity was observed (Table 2, entry 9).
Catalyst screening
1
2
3
4
5
6
7
8
9
RuCl3/(TPPTS)3 (1%)
RuCl2/(TPPTS)3/SILPC (1%)
Ru(acac)3 (1%)
[Ru(TMHD)3] (1%)
RuCl3–EDTA (1%)
[RuCl2(p-cymene)]2 (1%)
[RuCl2(p-cymene)]2/PPh3 (1%)
[RuCl2(p-cymene)]2/DPPE (1%)
[RuCl2(p-cymene)]2/DPPB (1%)
20
30
17
50
Trace
62
70
78
75
65 : 35
68 : 32
70 : 30
77 : 23
—
78 : 22
91 : 09
93 : 07
91 : 09
The inuence of CO2 pressure for vinyl carbamates synthesis
was then investigated. It was observed that increasing the
pressure from 4 MPa to 5 MPa resulted increase in the yield and
selectivity of the Z-isomer (Table 2, entries 10–12). Further
increase in the pressure to 7 MPa had no profound effect on the
reaction yield and selectivity (Table 2, entry 12). Hence, the best
optimized reaction parameters for regioselective synthesis of
vinyl carbamates were phenylacetylene, diethylamine and
carbon dioxide are: Ru[Cl2(p-cymene)]2 (1.0 mol%), DPPE
(1 mol%), solvent (ACN, 10 mL), diethylamine (4 mmol), CO2
Catalyst Loading
10
11
12
[RuCl2(p-cymene)]2/DPPE (0.3%)
[RuCl2(p-cymene)]2/DPPE (0.6%)
[RuCl2(p-cymene)]2/DPPE (1.5%)
43
64
78
92 : 08
92 : 08
93 : 07
ꢀ
pressure (5 MPa), temperature 80 C, time 24 h.
a
Reaction conditions: phenyl acetylene (2 mmol), diethyl amine
(4 mmol), metal : ligand ratio (1 : 1), ACN (10 mL), CO2 pressure
(5 MPa), temp. (80 ꢀC), time (24 h). b Yield based on GC analysis.
With these optimized reaction conditions in hand, we
investigated the scope and generality of the developed protocol
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 23022–23026 | 23023

View Article Online
RSC Advances
Communication
Table 2 Effect of reaction parameters on vinyl carbamate synthesis Table 3 The synthesis of vinyl carbamates from alkynes, secondary
a
a
from phenyl acetylene, diethyl amine and CO2
amines and CO2
Temp. CO2
Time Yieldb
(%)
Selectivity
(2a : 2b)
S. no. Solvent
(ꢀC)
(MPa) (h)
Effect of solvent
1
2
3
4
5
6
7
Toluene
DMF
THF
80
80
80
80
80
80
80
5
5
5
5
5
5
5
24
24
24
24
24
24
24
30
15
49
78
21
50
10
90 : 10
89 : 11
93 : 07
93 : 07
90 : 10
88 : 12
—
Alkynes
(R1)
Secondary amines
(R2)
Yieldb
(%)
Selectivity
2a : 2b
ACN
Entry
1
1,4-Dioxane
Glycerol
Water
78
61
93 : 07
91 : 09
Effect of temperature
8
9
ACN
ACN
60
100
5
5
24
24
38
54
93 : 07
89 : 11
2
3
Effect of CO2 pressure
10
11
12
ACN
ACN
ACN
80
80
80
3
4
7
24
24
24
47
70
80
77 : 23
93 : 07
91 : 09
47
63
89 : 11
90 : 10
Effect of time
4
13
14
15
ACN
ACN
ACN
80
80
80
5
5
5
12
18
30
62
69
80
93 : 07
93 : 07
93 : 07
a
Reaction conditions: phenyl acetylene (2 mmol), diethyl amine
(4 mmol), catalyst (1 mol%), DPPE (1 mol%), ACN (10 mL), CO2
5
6
7
8
9
49
87
84
63
88 : 12
97 : 03
98 : 02
93 : 07
b
pressure (5 MPa), temp. (80 ꢀC), time (24 h). Yield based on GC
analysis.
for the synthesis of variety of vinyl carbamates. Various alkynes
and secondary amines with different steric and electronic
properties were screened (Table 3, entries 1–10). The addition
reaction of diethyl amine and CO2 to phenylacetylene under the
optimized reaction conditions providing a 78% isolated yield
of the [(diethylcarbamoyl)oxy]styrene and (Z)-b-[(diethyl-
carbamoyl)oxy]styrene isomer with 93 : 07 selectivity and along
with small amount of dimmer of phenyl acetylene as biproduct.
Dibutyl amine was also found to react efficiently with phenyl
acetylene providing an excellent selectivity of (Z)-b-[(di-
butylcarbamoyl)oxy]styrene isomer up to 91%. Alicyclic amines
like morpholine and piperidine were found to provide good
yield and selectivity of [(morpholinocarbamoyl)oxy]styrene and
[(piperidinocarbamoyl)oxy] styrene isomer respectively (Table 3,
entries 3–5). Further we screened N-methyl-1-phenylmethan-
amine and diallylamine and were found to furnish good yield
and selectivity toward the formation of desire product (Table 3,
entries 6 and 7).
The present catalytic system was also worked well with the
electron donating and withdrawing aromatic substituted
alkynes providing good conversions with excellent selectivity
(Table 3, entries 8 and 9). Moreover, we also studied the
aliphatic alkyne such as 1-hexyne; reacted under the present
conditions to afford moderate yield of [(diethylcarbamoyl) oxy]-
hex-1-ene (Table 3, entry 10). Thus, improved yield and excellent
selectivity was observed for various vinyl carbamates under the
developed catalytic protocol as compared to earlier reports.
Et2NH
Et2NH
Et2NH
57
48
89 : 11
77 : 23
10
a
Reaction conditions: alkynes (2 mmol), secondary amine (4 mmol),
catalyst (1 mol%), DPPE (1 mol%), ACN (10 mL), CO2 pressure
(5 MPa), temp. (80 ꢀC), time (24 h). b Isolated yield.
The plausible mechanism of addition reactions of secondary
amine and CO2 to terminal alkynes for vinyl carbamate
synthesis was shown in Scheme 3. Firstly, the rearrangement of
ruthenium complex of type (I) into metal derivatives of type (II)
takes place, which show electrophilic behavior of the carbon
atom bonded to the metal center. Subsequent addition of
carbamates to the electrophilic carbon of this vinylidene–
ruthenium molecule (II) to give the intermediate (III).13 Subse-
quently, the ammonium cation [(R2)2NH2 ] formed during the
course of reaction which protonates the Ru metal followed by
classical reductive elimination from (IV), leading to the enol
+
23024 | RSC Adv., 2014, 4, 23022–23026
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
and stirred for 24 h at 600 rpm. Aer completion of reaction, the reactor was
cooled to room temperature and the remaining carbon dioxide was carefully
vented and then the reactor was opened. The crude product which was then
puried by column chromatography on silica gel (100–200 mesh size), with
petroleum ether–ethyl acetate (PE–EtOAc, 80 : 20) as eluent to afford a pure
product. The products were further characterized by GCMS analysis, 1H NMR and
13C NMR spectra (Varian 300 MHz NMR Spectrometer) using TMS as internal
standard. GCMS analysis was done on Shimadzu-QP2010 mass spectrometer
(Shimadzu GC-MS QP 2010) (Rtx-17, 30 m ꢁ 25 mm ID, lm thickness 0.25 mm df)
(column ow 2 mL minꢂ1, 80 ꢀC to 240 ꢀC at 10 ꢀC minꢂ1 rise).
1 T. Sakakura, J. C. Choi and H. Yasuda, Chem. Rev., 2007, 107,
2365; P. G. Jessop, T. Ikariya and R. Noyori, Chem. Rev., 1995,
95, 259; M. Mikkelsen, M. Jørgensen and F. C. Krebs, Energy
Environ. Sci., 2010, 3, 43–81.
2 P. T. Anastas and R. L. Lankey, Green Chem., 2000, 2, 289;
A. J. Hunt, E. H. K. Sin, R. Marriott and J. H. Clark,
ChemSusChem., 2010, 3, 306; T. Sakakura, J. C. Choi and
H. Yasuda, Chem. Rev., 2007, 107, 2365.
Scheme 3 Plausible reaction mechanism.
3 (a) S. Boivin, A. Chettouf, P. Hemery and S. Boileau, Polym.
Bull., 1983, 9, 114; (b) R. J. Khur and H. W. Dorough,
Carbamate insecticide: chemistry, biochemistry and toxicology,
CRS Press, Cleveland OH, 1976.
4 (a) S. I. Murahashi, Y. Mitsue and K. Ike, J. Chem. Soc., Chem.
Commun., 1987, 125; (b) S. Cenini, M. Pizzotti, C. Crotti,
F. Porta and G. La Monica, J. Chem. Soc., Chem. Commun.,
1984, 1286.
5 (a) R. A. Olofson, G. P. Wooden and J. T. Marks, Eur. Pat.
104984, Chem. Abstr., 1984, 101, 190657; (b) B. R. Franco-
Filipasic and R. Patarcity, Chem. Ind., 1969, 8, 166.
6 C. G. Overberger, H. Ringsdorf and N. Weinshenker, J. Org.
Chem., 1962, 27, 4331.
7 (a) R. A. Olofson, B. A. Bauman and D. J. Vancowicz, J. Org.
Chem., 1978, 43, 752; (b) R. A. Olofson, R. C. Schnur,
L. Bunes and J. P. Pepe, Tetrahedron Lett., 1977, 1567.
8 (a) S. Inoue and N. Yamazaki, Organic and bio-organic
chemistry of carbon dioxide, Kodansha, Tokyo, 1982; (b)
A. Aresta and G. Forti, Carbon dioxide as a source of
carbon; Reidal: NATO ASIseries C 206, 1987; (c) D. Walther,
H. Schonberg, E. Dinjus and J. S. Sieler, J. Organomet.
Chem., 1987, 334, 377.
carbamate. An alternative route could be protonolysis of the Ru–
C bond (III) followed by 1–2 shi of hydrogen atom giving
intermediate (VI), which on further de-coordination afford
desired product.13b
In summary, RuCl2(p-cymene)/DPPE catalytic system has
shown to be an efficient transition-metal catalyzed process for
the synthesis of alkenyl carbamates via three-component addi-
tion of secondary amines and CO2 to terminal alkynes. The
characteristic feature of present catalytic protocol is the high
regioselectivity giving the anti-Markovnikov adducts in good to
excellent yield. The different alkynes and secondary amines
with different steric and electronic properties were explored for
synthesis of alkenyl carbamates. The catalyst is highly stable
and shows an excellent catalytic activity under optimized
condition make it an ideal catalyst for regioselective synthesis of
vinyl carbamate.
Acknowledgements
The author (R. A. Watile) is greatly thankful to Council of
Scientic and Industrial Research (CSIR, India) for providing
nancial support (CSIR-SRF).
9 (a) Y. Sasaki and P. H. Dixneuf, J. Chem. Soc., Chem.
Commun., 1986, 790; (b) R. Mahe, Y. Sasaki, C. Bruneau
and P. H. Dixneuf, J. Org. Chem., 1989, 54, 1518; (c)
C. Bruneau and P. H. Dixneuf, J. Mol. Catal., 1992, 74, 97;
(d) H. J. Reich, R. C. Holtan and S. L. Borkowsky, J. Org.
Chem., 1987, 52, 314.
10 (a) T.-A. Mitsudo, Y. Hori, Y. Yamakawa and Y. Watanabe,
Tetrahedron Lett., 1987, 28, 4417; (b) M. Rohr, C. Geyer,
R. Wandeler, M. S. Schneider, E. F. Murphy and A. Baiker,
Green Chem., 2001, 3, 123.
11 (a) F. Simal, D. Jan, L. Delaude, A. Demonceau,
M.-R. Spirlet and A. Noels, Can. J. Chem., 2001, 79, 529;
(b) D. Enders, K. Breuer, G. Raabe, J. Runsink, H. Teles,
J.-P. Melder, K. Ebel and S. Brode, Angew. Chem., Int. Ed.
Engl., 1995, 34, 1021; (c) K. Melis, P. Samulkiewicz,
J. Rynkowski and F. Verpoort, Tetrahedron Lett., 2002,
43, 2713.
Notes and references
‡ Experimental
All chemicals and reagents were purchased from rms of repute with their highest
purity available and were used without further purication. [RuCl2(p-cymene)]2
precursor and phosphine ligands were purchased from Sigma-Aldrich. The reac-
tion mixture was analyzed by GC (Perkin-Elmer, Clarus 400) equipped with a ame
ionization detector (FID) and a capillary column (Elite-1, 30 m ꢁ 0.32 mm ꢁ 0.25
mm). The crude product was puried by column chromatography on silica gel
(eluting with 80 : 20 petroleum ether–ethyl acetate) to afford the product.
General procedure for synthesis of vinyl carbamate from CO2
In a typical experimental procedure, the alkynes (2 mmol), secondary amine
(4 mmol), [RuCl2(p-cymene)]2 (1 mol%), DPPE (1 mol%) and ACN (10 mL) were
charged into a 100 mL stainless steel autoclave with a mechanical stirrer at room
temperature. The autoclave was ushed with carbon dioxide and reaction mixture
was then pressurized to 5 MPa of CO2 pressure; the reactor was heated to 80 ꢀC
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 23022–23026 | 23025

View Article Online
RSC Advances
Communication
12 (a) Y. P. Patil, P. J. Tambade, N. S. Nandurkar and
B. M. Bhanage, Catal. Commun., 2008, 9, 2068; (b)
Y. P. Patil, P. J. Tambade, S. R. Jagtap and B. M. Bhanage,
J. Mol. Catal. A: Chem., 2008, 289, 14; (c) R. A. Watile,
Tetrahedron Lett., 2011, 52, 6383; (e) D. B. Nale, S. Rana,
K. M. Parida and B. M. Bhanage, Appl. Catal., A, 2014, 469,
340; (f) R. A. Watile, K. M. Deshmukh, K. P. Dhake and
B. M. Bhanage, Catal. Sci. Technol., 2012, 2, 1051.
D. B. Bagal, K. M. Deshmukh, K. P. Dhake and 13 (a) M. I. Bruce and A. G. Swincer, Adv. Organomet. Chem.,
B. M. Bhanage, J. Mol. Catal. A: Chem., 2011, 351, 196; (d)
R. A. Watile, D. B. Bagal, Y. P. Patil and B. M. Bhanage,
1983, 22, 59; (b) M. S. Brookhart, J. R. Tucker and
G. R. Husk, J. Am. Chem. Soc., 1983, 105, 258.
23026 | RSC Adv., 2014, 4, 23022–23026
This journal is © The Royal Society of Chemistry 2014