A moisture- and air-stable cationic ruthenium complex as catalyst for highly atom-economical stereo- and regioselective vinylation of azoles

Article abstract of DOI:10.1002/chem.201103424

Vinylation of azoles: The cationic Ru^II complex, [RuCl(PPh ₃)(dppe)(CH₃CN)₂][BPh₄], is an efficient catalyst for regio- and stereoselective vinylation of azoles by alkynes (dppe=diphenylphosphinoethane; see scheme). Only 0.5 mol % of the complex is required and the reactions do not require stringent exclusion of moisture and air.

Full text of DOI:10.1002/chem.201103424

DOI: 10.1002/chem.201103424
A Moisture- and Air-Stable Cationic Ruthenium Complex as Catalyst for
Highly Atom-Economical Stereo- and Regioselective Vinylation of Azoles
Uttam Kumar Das and Manish Bhattacharjee*[a]
Dedicated to Professor Mihir K. Chaudhuri on the occasion of his 65th birthday
N-Vinyl amines are important starting materials for prep-
aration of polymeric dyes and ion-exchange resins. For ex-
ample, N-vinyl azoles have been shown to afford polymeric
materials, which show catalytic properties and photorefrac-
tive properties.[1] Moreover, some of the compounds have
been shown to be active against fungal infections.[2] In view
of the importance of N-vinyl azoles, various synthetic meth-
ods have been developed. The most important method is
the coupling of vinyl bromide to azoles mediated by metals,
such as Hg[3] or Pd.[4] Both methods suffer from disadvantag-
es. In recent years, there have been reports on CuI mediated
We have been interested in the synthesis of cationic ruthe-
nium complexes and studies of their catalytic properties and
have reported the synthesis and structure of [Ru
(CH3CN)3]
[BPh4].[13] This complex has been shown to acti-
vate alkynes for the C O bond formation.
report the synthesis, structure, and catalytic properties of
[Ru(dppe)(PPh3)(CH3CN)2Cl][BPh4] (1).
The complex has been synthesized from the reaction of
[RuCl2A(PPh3)3] with diphenylphosphinoethane (dppe) in
ACHTUNGTERN(NUNG PPh3)2Cl-
A
ACHTUNGTRENNUNG
[13d]
À
Herein we
A
E
N
ACHTUNGTRENNUNG
CTHUNGTRENNUNG
a 1:1 ratio in acetonitrile. The complex has been character-
1
ized by elemental analyses, IR, and H and 31P NMR spec-
C N bond formation via coupling of vinyl bromide/iodide
troscopy. The 1H NMR spectrum (CDCl3) of 1 is in good
agreement with other reported ruthenium dppe com-
plexes.[14] The 31P NMR spectrum (CDCl3) of 1 shows two
sharp singlets at 74.2 ppm, due to dppe, and 34.3 ppm, due
to coordinated PPh3. Note, at low temperature (À208C and
À
with amines in the presence of various ligands and large
amount of base, such as Cs2CO3.[5] The same method has
been used for vinylation of azoles.[1a,d,6] Most of these meth-
ods require either harsh conditions or longer reaction times
and high catalyst loadings. One method has recently been
reported, for which only 5 mol% catalyst and ligand is re-
quired, however, mainly vinyl iodide has been found to be
effective.[7] There are also reports on hydroamination of al-
kynes. However, most of the described methods afford the
Markovnikov addition product. Anti-Markovnikov hydroa-
mination of alkynes, catalyzed by actinides,[8] Rh,[9] and
Ti,[10] have been reported in the literature. Trisrutheniumdo-
decacarbonyl has been shown to catalyze vinylation of
azoles by alkynes. However, mixtures of stereoisomers were
obtained.[11] Thus, the methods are not atom economical or
suffer from other disadvantages. Recently it has been re-
1
À508C), the H and 31P NMR spectra remain unaltered, thus
ruling out the presence of fluxionality in solution.
The complex crystallizes in triclinic space group P-1. The
asymmetric unit contains one cationic ruthenium complex
(Figure 1) and one tetraphenylborate anion. The ruthenium
center is in a distorted octahedral coordination environment
and is coordinated to two acetonitrile nitrogens, N1 and N2,
one chloride, Cl1, and three phosphorus atoms, P1, P2, and
P3.
Appearance of two singlets in the 31P NMR spectrum
shows that, in solution the structure of the complex is differ-
ent from that at solid state. Based on the NMR studies we
suggest that, in solution, the complex looses one acetonitrile
ligand and the complex assumes a trigonal bipyramidal ge-
ometry (Figure S4 in the Supporting Information). Along
ported that, AgACHTUNGTRENNUNG(NO3)/AgHCATUNGTRNE(NUGN OTf) can catalyze single and
double addition of pyrazole to alkynes. However, for the
single addition, the catalyst loading is high and the reaction
conditions are harsh and mixtures of products were ob-
tained.[12] Note, in all the reactions, exclusion of air and
moisture is essential. In addition, vinyl halides are expensive
and all the methods of vinylation, described in the literature,
are not environment friendly.
1
with other signals, the H NMR spectrum of 1 shows a signal
À
(singlet) at 2.00 ppm due to CH3 protons of the free aceto-
nitrile ligand.
We were interested in studying the catalytic properties of
1 towards activation of unactivated alkynes for addition re-
actions. We have shown that cationic ruthenium complexes
are capable of activating alkynes towards addition reac-
tions[13d] and we wanted to explore the efficacy of 1 as cata-
lyst for the addition of alkynes to azoles. Thus, the addition
of 3,5-dimethylpyrazole (2a) to phenylacetylene (3a) was
chosen as a model reaction. As shown in Table 1, when the
addition reaction of 2a to 3a was carried out in the presence
of a catalytic amount of 1 in toluene at 508C, a 4:1 mixture
[a] U. K. Das, Prof. Dr. M. Bhattacharjee
Department of Chemistry
Indian Institute of Technology
Kharagpur 721 302 (India)
Fax : (+91)3222-282252
E-mail: mxb@iitkgp.ac.in
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201103424.
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Chem. Eur. J. 2012, 18, 5180 – 5183

COMMUNICATION
Having established the optimum condition, we were inter-
ested in studying the scope of the reaction. Thus, a number
of substituted pyrazoles were vinylated by both aliphatic
and aromatic alkynes (Scheme 1, Table 2) in moderate to
high yields (70 to 95%). Besides pyrazoles, benzotriazole
also could be vinylated (entry 13). One of the new com-
pounds, 2-[5-(3,5-dimethyl-pyrazol-1-yl)pent-4-en-1-yl]-isoin-
dole-1,3-dione (4e), has been structurally characterized by
single-crystal X-ray crystallography. The ORTEP view of
the compound is shown in Figure 2. The X-ray structure
(CH3CN)2Cl]+ with thermal
Figure 1. ORTEP view of [RuACHTUNGRTEN(NNGU dppe)ACHTNUTRGEG(NUNN PPh3)ACHTNUGTRENNUGN
ellipsoids drawn in 30% probability. Hydrogen atoms have been omitted
for clarity.
Scheme 1. Reaction between azoles and alkynes catalyzed by 1. 2a: R1 =
R2 =CH3, R3 =H; 2b: R1 =R2 =R3 =CH3; 2c: R1 =Ph, R2 =CH3, R3 =H;
2d: R1 =R2 =Ph, R3 =H; 3a: R4 =Ph; 3b: R4 =C4H9; 3c: R4 =cy-
cloC6H11; 3d: R4 =4-phenoxyphenyl; 3e: R4 =isoindole-1,3-dione-2-
propyl.
Table 1. Optimization of reaction between 3,5-dimethylpyrazloe and phe-
nylacetylene catalyzed by 1.[a]
Entry
Solvent
Temp [8C]
t [h]
Yield [%][b]
E/Z[c]
Table 2. Vinylation of azoles catalyzed by 1.[a]
1
2
3
4
5
6
7
8
9
acetonitrile
dioxane
DMF
toluene
toluene
toluene
toluene
toluene
toluene
80
90
90
25
50
12
12
12
24
12
12
12
12
8
trace
25
no reaction
no reaction
30
50
95
95
95
–
–
–
Entry
Azole
Alkyne
Product
Yield [%][b]
E/Z[c]
1
2
3
4
5
6
7
8
2a
2a
2a
2a
2a
2b
2b
2b
2c
2c
2d
2d
2e
3a
3b
3c
3d
3e
3a
3b
3c
3b
3e
3a
3e
3a
4a
4b
4c
4d
4e
4 f
4g
4h
4i
95
90
95
85
85
90
75
82
78
75
75
70
85
–
9:1
–
–
–
–
3:1
–
5:3
–
–
–
4:1
4:1
99:1
99:1
99:1
80
100
110
100
[a] Reaction conditions: phenylacetylene (1.0 mmol), 3,5-dimethylpyra-
zole (1.0 mmol), 1 (0.5 mol%) in solvent (5.0 mL). [b] Isolated. [c] From
NMR spectroscopy.
9
10
11
12
13
4j
4k
4l
5:2
2:1
4m
of E and Z isomers was obtained in 30% yield. As the tem-
perature was increased to 1008C, the E isomer was obtained
exclusively. The effect of solvents on the model reaction was
also examined. Among the solvents, such as acetonitrile,
DMF, toluene, and dioxane, toluene was found to be the
best choice (entries 5–9). The effect of the reaction tempera-
ture and time on the addition reaction was also investigated.
We found that the reaction was complete when carried out
at 1008C for 8 h in the presence of 1 (0.5 mol%; entry 9)
and no significant improvement was observed when 1.0
mol% of catalyst was used. In the absence of 1, the reaction
does not take place. To check the Brønsted acid catalysis,
the reaction was carried out in the presence of triflic acid
and in the absence of 1, however, we could not detect any
product formation. Also, reactions carried out in the pres-
ence of [Ru(CO)3Cl2]2 failed to give any product.
[a] Reaction conditions: alkyne (1.0 mmol), azole (1.0 mmol),
1 (0.5 mol%), toluene (5.0 mL), T=1008C. [b] Isolated. [c] From NMR
spectroscopy.
Figure 2. ORTEP view of 4e with thermal ellipsoids drawn in 30% prob-
ability. Hydrogen atoms have been omitted for clarity.
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U. K. Das and M. Bhattacharjee
confirms the trans geometry of the compound. Interestingly,
the addition reaction is highly regiospecific as shown by the
reaction of 3-methyl-5-phenyl-1H-pyrazole (2c) with 1-
hexyne (3b) and 2-pent-4-enyl-isoindole-1,3-dione (3e).
NOESY spectra of 4i and 4j (see the Supporting Informa-
tion) clearly show the interaction between the phenyl and
the vinyl protons, but no interaction between the methyl
and the vinyl protons. Thus, it is clear that, vinylation takes
place exclusively on N1. Similarly, the vinylation reaction is
highly stereoselective and almost exclusively gives the E
product, except in the cases of 4b, 4g, 4i, 4l, and 4m
(Table 2), for which mixtures of Z (minor) and E (major)
isomers were obtained (Table 2, entries 2, 7, 9, 12, and 13).
We were interested in studying the mechanism through in
1
situ 31P and H NMR spectroscopy. The 31P NMR spectrum
of the complex shows two singlets at 34.3 and 74.2 ppm.
When 3,5-dimethylpyrazole is added (1:1 ratio) to this solu-
tion, the peak at 34.3 ppm shifts to 33.8 ppm. Thus it is clear
that, 3,5- dimethylpyrazole gets coordinated to the rutheni-
um center. Similarly, when phenylacetylene is added (1:1
ratio) to a solution of complex 1, the peaks shift to 33.5 and
73.9 ppm, respectively. Thus, phenylacetylene also gets coor-
Scheme 2. Proposed mechanism of vinylation of azoles catalyzed by 1.
1
dinated to the ruthenium center. The H NMR spectrum of
LnRu+ =[Ru (PPh3)Cl]+.
ACTHNUTRGENNU(G dppe)ACHTUTGNRENNUGN
the mixture of 1 and phenylacetylene shows a singlet at
3.40 ppm, along with other signals. This has been assigned to
the ruthenium-coordinated vinylidene proton. This assign-
ment is in good agreement with the H NMR spectrum of
the reported ruthenium vinylidene complex, [(p-
addition reaction is highly atom economical and regio- and
stereoselective. The catalyst loading is very low (0.5 mol%)
and the complex is stable in air and moisture, hence, strin-
gent exclusion of air and moisture is not necessary.
1
Cymene)RuACHTUNGTRENNUNG(m-Cl)3RuClACHTUNRTGENN(GUN CCHPh)CAHTNUGTREN(GUNN IMes)] (IMes=1,3-dime-
setylimidazole-2-yilidene).[15] When both the reactants are
added to the solution of complex 1 and heated to 1008C,
two intense peaks (singlets) appear at 33.8 and at 79.3 ppm.
These peaks may be assigned to the vinylidene complex,
Experimental Section
[Ru
(dppe)
E
E
(dmpz)Cl]+
(Scheme 2;
B,
Synthesis: RuCl2ACTHNUTRGNEUGN(PPh3)3 (2.0 g; 2.1 mmol) and 1,2-bis(diphenylphosphi-
dmpz=3,5-dimethylpyrazole). Along with these two major
peaks, three small peaks appear at 59.6, 66.9, and 71.8 ppm.
These peaks may be assigned to reaction intermediate C
(Scheme 2). Based on the above studies we propose a mech-
anism that is been shown in Scheme 2. The first step is the
replacement of coordinated acetonitrile by the pyrazole
ligand to produce A. This is followed by coordination of the
alkyne and rearrangement to the vinylidene species B. Next,
the coordinated vinylidene carbon is exposed to a nucleo-
philic attack by the pyrazole nitrogen and finally the prod-
uct is released by protonolysis. Note, reaction of the internal
alkyne, diphenylacetylene, with 2,3-dimethylpyrazole failed
to give the addition product. This clearly indicates that, the
mechanism involves a vinylidene intermediate.
Interestingly, vinylation reactions of benzimidazole, pyr-
role, and indole failed to give any product and only starting
materials were recovered. Similarly, reactions of diphenyla-
mine with phenylacetylene also failed to give the addition
product. This clearly shows that the presence of two nitro-
gen atoms adjacent to each other is necessary; this in turn
supports the suggested mechanism.
no)ethane (0.85 g; 2.1 mmol) were dissolved in acetonitrile (10 mL) and
the reaction solution was refluxed for about 2.5 h. The color of the reac-
tion solution turned brown to light yellow. The reaction solution was
then filtered and NaBPh4 (0.72 g; 2.1 mmol) was added. The solution was
concentrated over a water bath. A yellow, crystalline solid separated out.
The separated solid was filtered and washed with hexane (3–4 times) and
dried in vacuum. The compound was finally recrystallized from acetoni-
trile. Yield: 1.91 g (80%): 1H NMR (200 MHz, CDCl3, ppm): d=1.99 (s,
6H), 2.60 (d, J=15.2 Hz, 4H), 6.89–7.97 (m, 55H); 31P NMR
(161.98 MHz, CDCl3, ppm): d=34.3, 74.2 ppm; IR (KBr): u˜ =486, 696,
743, 1093, 1179, 1432, 1479, 1579, 2273, 2916, 2981, 3051 cmÀ1; elemental
analysis: calcd for C72H65BClN2P3Ru: C 72.15, H 5.47, N 2.34; found: C
72.20, H 5.54, N 2.35.
General procedure for the synthesis of N-vinyl pyrazole: The alkyne
(1 mmol) and [RuACHTNUGTREN(UNNG dppe)CAHUTGTNRENNGU(PPh3)ACHTUNGETRNNG(NU CH3CN)2Cl]ACHTUNGTREN[NUGN BPh4] (0.006 g, 0.005 mmol)
were placed in a round-bottom flask fitted with a condenser and a stirring
bar. Toluene (5 cm3) was added, followed by the azole (1 mmol). The re-
action mixture was then heated and stirred for 8 h in an oil bath. After
8 h of stirring, the round-bottom flask was removed from the heating
bath and cooled to room temperature. The solvent and other volatile
components were removed in vacuo. The resulting products were purified
by column chromatography.
X-ray structures: The structures were solved by direct methods and re-
fined by least square methods on F2 employing WinGx[16] package and
the relevant programs (SHELX-97[17] and ORTEP-3[18]) implemented
therein. Non-hydrogen atoms were refined anisotropically and hydrogen
atoms on C atoms were fixed at calculated positions and refined by using
In conclusion, complex 1 has been found to be an effec-
tive catalyst for hydroamination of alkynes by azoles. The
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Chem. Eur. J. 2012, 18, 5180 – 5183

Vinylation of Azoles
COMMUNICATION
a riding model. In compound 4e the hydrogen atoms on C6 and C7 were
located in Fourier difference map and refinement was done by a mixed
method. CCDC-827295 (1) and CCDC-827296 (4e) contain the supple-
mentary crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[3] a) V. N. Kizhnyaev, F. A. Pokatilov, N. A. Tsypina, G. V. Ratovskii,
L. I. Vereshchagin, A. I. Smirnov, Russ. J. Org. Chem. 2002, 38,
1056–1059.
[4] a) A. Y. Lebedev, V. V. Izmer, D. N. Kazyulꢂkin, I. P. Beletskaya,
A. Z. Voskoboynikov, Org. Lett. 2002, 4, 623–626; b) J. R. Dehli, J.
Legros, C. Bolm, Chem. Commun. 2005, 973–986.
[5] a) Y. Fukudome, H. Naito, T. Hata, H. Urabe, J. Am. Chem. Soc.
2008, 130, 1820–1821; b) R. Martꢃn, A. Cuenca, S. L. Buchwald,
Org. Lett. 2007, 9, 5521–5524; c) R. Martꢃn, C. H. Larsen, A.
Cuenca, S. L. Buchwald, Org. Lett. 2007, 9, 3379–3382; d) A. Shafir,
P. A. Lichtor, S. L. Buchwald, J. Am. Chem. Soc. 2007, 129, 3490–
3491.
[6] a) Q. Liao, Y. Wang, L. Zhang, C. Xi, J. Org. Chem. 2009, 74, 6371–
6373; b) Z. Wang, W. Bao, Y. Jiang, Chem. Commun. 2005, 2849–
2851.
Crystal data for 1: C72H65ClN2P3Ru, Mr =1198.5, 293(2) K, triclinic, P-1,
a=12.0370(16), b=15.027(2), c=18.103(3) ꢁ, a=108.610(4)8, b=
99.988(4)8, g=92.592(4)8, V=3038.4(8) ꢁ3, Z=2, l=0.71073 ꢁ, reflec-
tions collected/unique=41130/13630,
Rint =0.079, R1=0.074, wR2=
0.1798 for 8371 observed reflections [I>2s(I)].
Crystal data for 4e: C18H19N3O2, Mr =309.36, 293(2) K, monoclinic, P21/
n, a=8.5022(12), b=16.219(2), c=11.9241(17) ꢁ, b=93.472(5)8, V=
1641.3(4) ꢁ3, Z=4, l=0.71073 ꢁ, reflections collected/unique=21581/
4135, Rint =0.0781, R1=0.0597, wR2=0.1363 for 1922 observed reflec-
tions [I>2s(I)].
[7] M. S. Kabir, M. Lorenz, O. A. Namjoshi, J. M. Cook, Org. Lett.
2010, 12, 464–467.
[8] A. Haskel, T. Straub, M. S. Eisen, Organometallic 1996, 15, 3773–
3775.
[9] a) K. Sakai, T. Kochi, F. Kakiuchi, Org. Lett. 2011, 13, 3928–3931;
b) Y. Fukumoto, H. Asai, M. Shimizu, N. Chatani, J. Am. Chem.
Soc. 2007, 129, 13792–13793; c) C. Alonso-Moreno, F. Carrillo-Her-
mosilla, J. Romero-Fernꢄndez, A. M. Rodrꢃguez, A. Otero, A. Anti-
Çolo, Adv. Synth. Catal. 2009, 351, 881–890.
[10] Z. Zhang, L. L. Shafer, Org. Lett. 2003, 5, 4733–4736.
[11] N. Tanaka, M, Hatanaka, Y. Watabe, JP Pat. 1026, 1993.
[12] T. Tsuchimoto, K. Aoki, T. Wagatsuma, Y. Suzuki, Eur. J. Org.
Chem. 2008, 4035–4040.
Acknowledgements
We thank the Department of Science & Technology, Government of
India, New Delhi for single crystal X-ray and NMR-spectroscopy facili-
ties. UKD thanks CSIR, New Delhi, India for a fellowship. We thank
Prof. Amit Basak of the Department of Chemistry, Indian Institute of
Technology, Kharagpur, India for helpful discussion on NOESY. We
thank the reviewers for their helpful comments.
[13] a) S. Naskar, M. Bhattacharjee, J. Organomet. Chem. 2005, 690,
5006–5010; b) S. Naskar, M. Bhattacharjee, Tetrahedron Lett. 2007,
48, 465–467; c) S. Naskar, M. Bhattacharjee, Tetrahedron Lett. 2007,
48, 3367–3370; d) J. Tripathy, M. Bhattacharjee, Tetrahedron Lett.
2009, 50, 4863–4865.
Keywords: alkynes
vinylation
· azoles · catalysis · ruthenium ·
[14] a) B. Chin, A. J. Lough, R. H. Morris, C. T. Schweitzer, C. DꢂAgosti-
no, Inorg. Chem. 1994, 33, 6278–6288; b) M. T. Bautista, E. P. Cap-
pellan, S. D. Drouin, R. H. Morris, C. T. Schweitzer, A. Sella, J Zub-
kowski, J. Am. Chem. Soc. 1991, 113, 4876–4887.
[15] Y. Borguet, X. Sauvage, G. Zaragoza, A. Domonceau, L. Delaude,
Organometallics 2011, 30, 2730–2738.
[16] L. J. Farrugia, J. Appl. Crystallogr. 1999, 32, 837–838.
[17] G. M Sheldrick, Acta Crystallogr. A 2008, 64, 112.
[18] L. J. Farrugia, J. Appl. Crystallogr. 1997, 30, 565.
[1] a) M. Taillefer, A. Ouali, B. Renard, J.-F. Spindler, Chem. Eur. J.
2006, 12, 5301–5313; b) W. Bao, Y. L. Xin Lv, Synthesis 2008, 12,
1911–1917; c) A. Ouali, R. Laurent, A.-M. Caminade, J.-P. Majoral,
M. Taillefer, J. Am. Chem. Soc. 2006, 128, 15990–11991; d) H. Kad-
douri, V. Vicente, A. Ouali, F. Ouazzani, M. Taillefer, Angew. Chem.
2009, 121, 339–342; Angew. Chem. Int. Ed. 2009, 48, 333–336; e) F.
Brustolin, V. Castelvetro, F. Ciardelli, G. Ruggeri, A. Colligiani, J.
Polym. Sci. A: Polym. Chem. 2001, 39, 253–262.
[2] M. Ogata, H. Matsumoto, S. Shimizu, S. Kida, M. Shiro, K. Tawara,
J. Med. Chem. 1987, 30, 1348–1354.
Received: November 1, 2011
Published online: March 20, 2012
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5183