Hydrazinoaminocarbene-palladium complexes as easily accessible and convenient catalysts for copper-free Sonogashira reactions

Article abstract of DOI:10.1016/j.tetlet.2014.02.044

Two easily accessible hydrazinoaminocarbene complexes of Pd(II) are shown to be efficient catalysts for copper-free Sonogashira cross-couplings of a variety of aryl iodides with aryl- and alkylalkynes under mild conditions, in ethanol as the solvent and u

Full text of DOI:10.1016/j.tetlet.2014.02.044

Tetrahedron Letters 55 (2014) 2101–2103
Contents lists available at ScienceDirect
Tetrahedron Letters
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Hydrazinoaminocarbene–palladium complexes as easily accessible
and convenient catalysts for copper-free Sonogashira reactions
a,b,
⇑
a
b
a
Elizaveta A. Savicheva
, Daria V. Kurandina , Vladimir A. Nikiforov , Vadim P. Boyarskiy
a
Department of Chemistry, Saint-Petersburg State University, Universitetskiy pr. 26, 198504 Saint-Petersburg, Russia
Scientific Research Center for Ecological Safety of Russian Academy of Sciences, Korpusnaya st. 18, 197110 Saint-Petersburg, Russia
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Two easily accessible hydrazinoaminocarbene complexes of Pd(II) are shown to be efficient catalysts for
copper-free Sonogashira cross-couplings of a variety of aryl iodides with aryl- and alkylalkynes under
mild conditions, in ethanol as the solvent and using potassium carbonate as the base. The reactions were
carried out with 0.05 mol % of the catalysts which demonstrated exceptional stability in the solid state
and in ethanol. Protection from air is not needed. Disubstituted acetylenes were synthesized by the
general procedure on up to a gram scale and the yields were 80–98%.
Received 12 October 2013
Revised 30 January 2014
Accepted 13 February 2014
Available online 22 February 2014
Keywords:
Copper-free Sonogashira reaction
Cross-coupling
Ó 2014 Elsevier Ltd. All rights reserved.
Acyclic diaminocarbene palladium
complexes
Aryl hydrazines
Isocyanides
Sonogashira cross-coupling of monosubstituted acetylenes and
aryl halides catalyzed by palladium and copper species is a com-
mon route to disubstituted acetylenes.1 However, the presence
of a copper co-catalyst may lead to unwanted side reactions such
Cl
Cl
CNCy
I or II
EtOH, K CO
ArI
RCCH
Ar
R
Pd
NHCy
–3
2
3
8
0-98%
HN
2–4
NRR'
as the formation of diynes
or further cyclization of the target
complex I: R=H; R'=4-NO
2 6 4
C H
5
products. Also, it is worth noting that copper is not environmen-
tally friendly and the use of relatively large amounts of copper
complex II: R=R'=Ph
6
should be avoided. Copper-free Sonogashira reactions have been
Scheme 1. Copper-free Sonogashira reaction.
known for a long time,7 but initially required harsh conditions
and large amounts of palladium catalysts. The development of
more active catalysts has allowed copper-free Sonogashira
An attractive alternative to Pd–NHCs with equal or superior cat-
alytic activity in cross-coupling reactions is palladium(II) com-
plexes with acyclic diaminocarbenes (Pd–ADC).
one report in the literature on the use of a Pd–ADC as a catalyst
8–13
reactions to be performed under milder conditions.
An impressive advance was the use of just 0.001 mol % of a
catalyst for copper- and amine-free Sonogashira coupling of aryl
iodides, bromides, and chlorides with unsubstituted phenylacety-
lene. This was achieved with specialized five- or seven-membered
palladacycles based on phosphine-ylide ligands.8
11–15
There is only
12
for the copper-free Sonogashira reaction. However, the catalyst
was prepared by a rather complicated method involving pretreat-
ment of a specially synthesized formamidinium salt with LDA.
We earlier reported the acyclic hydrazinoaminocarbene palla-
dium complex I and demonstrated its good catalytic activity in a
variety of classic cross-coupling reactions.
b,c
More typical and simple are Pd–NHC complexes (NHC = N-het-
9
erocyclic carbene). They show good activity in classic and copper-
9
,10
free
Sonogashira reactions between aryl, heteroaryl, or alkyl
13–15
This complex was
halides with various acetylenes, but their preparation is often a
laborious task.
synthesized easily by the reaction of a known palladium(II) isocy-
anide complex (cis-[PdCl (C„NCy) ]) with 4-NO NHNH
2
2
2
C H
6 4
2
.
Herein, we report a convenient method for the copper-free
Sonogashira cross-coupling of aryl iodides with various terminal
acetylenes under mild conditions, catalyzed by complex I, as well
as by another hydrazinoaminocarbene complex, II (Scheme 1).
⇑
Corresponding author. Tel./fax: +7 812 499 64 55.
E-mail address: savicheva90@gmail.com (E.A. Savicheva).
http://dx.doi.org/10.1016/j.tetlet.2014.02.044
040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
0

2
102
E. A. Savicheva et al. / Tetrahedron Letters 55 (2014) 2101–2103
Catalysts I and II were prepared by the procedure described
previously for complex I (Scheme 2).13–15 The reaction between
equimolar amounts of cis-[PdCl (C„NCy) ] and the corresponding
(Table 2).18 We also tested two aryl bromides (4-bromotoluene and
4-nitrobromobenzene) with phenylacetylene using 1 mol % of the
palladium catalyst and carried out the reaction for 72 h (Table 2,
entries 21 and 22). The products were obtained in yields of 12%
and 62% (conversions were 15% and 62%), respectively. In all cases
(except for entries 6 and 11), full conversions of the aryl iodides
were achieved.
The reaction was found to be applicable to a variety of aryl
iodides with electron-donating (entries 2–4, 6, 10, 11, and 14) or
electron-withdrawing (entries 5, 7, 8, 12, 13, 16, 17, 19, and 20)
groups, and with one or even two ortho-substituents (entries 2,
4, 5, and 11). Terminal acetylenes with aryl-(entries 1–14) and
alkyl (entries 15–20) substituents could be employed.
The mass spectrum of the mixture after coupling iodobenzene
with 2-methylbut-3-yn-2-ol (entry 18) showed fragments with
m/z values of 162, 144, and 142. These data proved the presence
of by-products formed via dehydration and reduction of the target
product. Such by-products were not detected in the other
Sonogashira reactions that we carried out.
2
2
hydrazine proceeded to completion in four hours in 1,2-dichloro-
ethane at reflux, and subsequent work-up provided complexes I
and II in yields of 95% and 85%, respectively.16 Both complexes
are air- and moisture-stable in the 20À80 °C temperature range,
and are also stable as ethanol solutions for at least four months.
To study the catalytic activity of complexes I and II we chose
the reaction of phenylacetylene with 4-iodotoluene.17 Cheap and
environment-friendly ethanol and potassium carbonate were used
as the solvent and base, respectively, in order to find a catalytic
system operating under mild conditions. The reaction conditions
were optimized in a standard manner (the variables were temper-
ature, reaction time and amount of catalyst). The reactions were
carried out in screw-capped vials with rapid stirring. No special
measures were used to protect the reactions from air. The results
are presented in Table 1.
At room temperature, the reaction proceeded too slowly (en-
tries 1 and 2). At 80 °C, full conversion of 4-iodotoluene was
achieved in two hours and the yield of the product, as determined
by GC, was 97% (entry 3). It was possible to reduce the amount of
the catalyst to 0.05 mol % (entry 4) without decreasing the yield.
Further reduction of the amount of catalyst led to longer reaction
times in order to reach 100% conversion of the aryl iodide (entry
To demonstrate the synthetic abilities of the catalytic system,
we performed two experiments on a gram scale with PhI and
4-NO
obtained the corresponding coupling products in good (84%,
PhC„CPh) or excellent (95%, 4-NO C„CPh) preparative yields
2 6 4
C H I and phenylacetylene. Based on 20 mmol of ArI, we
2 6 4
C H
1
9,20
(entries 1 and 8).
6
). In addition, long reaction times affected the selectivity of the
In conclusion, we have reported a general and efficient method
to obtain disubstituted acetylenes. Two catalysts I and II belonging
to the family of ADC palladium complexes were shown to be active
in copper-free Sonogashira reactions under mild conditions. No
protection from air was needed. The catalysts can be prepared
easily and are stable as ethanol solutions for at least four months.
Environment-friendly ethanol proved to be a suitable solvent for
the reaction. The method allowed Sonogashira cross-coupling
products to be obtained in good to excellent preparative yields
(up to 95%) on gram scale.
reaction and a decrease in the yield of the desired product was
detected (entries 6 and 8). The following conditions were found
to be optimum for catalyst I: 0.05 mol % of catalyst, ethanol at
8
0 °C, and excess potassium carbonate (entry 4). Similar results
were obtained with catalyst II (entries 9–13) and the optimum
conditions were the same as for catalyst I (entry 10).
Next, the scope of the reaction was studied with catalyst I and
eight different aryl iodides and four terminal acetylenes under
optimized conditions, until 100% conversions (of ArI) were attained
NH -NRR', CHCl , r.t.
NCy
NCy
2
3
NCy
Cl
R=H; R'=4-NO C H
2 6 4
Cl
Cl
Pd
Pd
NHCy
Cl
NH -NRR', DCE, reflux
2
HN
NRR'
R=R'=Ph
complex I: R=H; R'=4-NO C H
6 4
complex II: R=R'=Ph
2
Scheme 2. Synthesis of the catalysts.
Table 1
1
7
Optimization of the reaction conditions (optimal conditions are in bold)
I or II
I
Ph
Ph
EtOH, K CO
2
3
air
Entry
Catalyst (mol %)
T (°C)
Time (h)
Conversion of 4-MeC
6
H
4
I (%)
6 4
Yield of 4-MeC H C„CPh (%)
1
2
3
4
5
6
7
8
9
I (0.1)
I (0.1)
I (0.1)
21
21
80
80
80
80
80
80
80
80
80
80
80
24
96
2
2
2
4
4
24
2
2
12
28
10
25
97
96
58
82
39
65
92
94
81
43
53
100
100
61
100
45
I (0.05)
I (0.02)
I (0.02)
I (0.01)
I (0.01)
II (0.1)
II (0.05)
II (0.02)
II (0.01)
II (0.01)
84
100
100
100
47
1
1
1
1
0
1
2
3
4
4
24
70

E. A. Savicheva et al. / Tetrahedron Letters 55 (2014) 2101–2103
2103
Table 2
8. (a) Kritchenkov, A. S.; Luzyanin, K. V.; Bokach, N. A.; Kuznetsov, M. L.; Gurzhiy,
V. V.; Kukushkin, V. Yu. Organometallics 2013, 1979, 32; (b) Sabounchei, S. J.;
Ahmadi, M. Catal. Commun. 2013, 37, 114; (c) Sabounchei, S. J.; Ahmadi, M.;
Nasri, Z.; Shams, E.; Panahimehr, M. Tetrahedron Lett. 2013, 54, 4656; (d)
Marziale, A. N.; Johannes, S.; Eppinger, J. Tetrahedron Lett. 2011, 52, 6355; (e)
Bakherad, M.; Keivanloo, A.; Bahramian, B.; Hashemi, M. Tetrahedron Lett. 2009,
1
8
Reactions of aryl iodides and bromides with terminal acetylenes
I (0.05 mol%)
ArX
R
Ar
R
EtOH, 80 °C
K CO , air
2
3
5
0, 1557.
9.
(a) Yus, M.; Pastor, I. M. Chem. Lett. 2013, 42, 94; (b) Fortman, G. C.; Nolan, S. P.
Chem. Soc. Rev. 2011, 40, 5151.
Entry
Ar-X
Ph-I
2-MeC
4-MeC
2,6-Me
2,4,6-Cl
4-MeOC
4-OHCC
4-NO
Ph-I
4-MeC
2,6-Me
4-NO
4-OHCC
4-MeOC
Ph-I
4-OHCC
4-NO
Ph-I
4-OHCC
4-NO
4-MeC
4-NO
R-C„CH
Yield of Ar-C„C-R (%)
1
0. (a) Dash, C.; Shaikh, M. M.; Ghosh, P. Eur. J. Inorg. Chem. 2009, 1608; (b)
Samantaray, M. K.; Shaikh, M. M.; Ghosh, P. J. Organomet. Chem. 2009, 694,
3477; (c) John, A.; Modak, S.; Madasu, M.; Katari, M.; Ghosh, P. Polyhedron
2013, 64, 20.
1
2
3
4
5
6
7
8
9
Ph-C„CH
Ph-C„CH
Ph-C„CH
Ph-C„CH
Ph-C„CH
Ph-C„CH
Ph-C„CH
Ph-C„CH
95 (84a)
96
96
6
H
H
4
-I
-I
6
4
2
C
6
H
3
-I
-I
94
11. (a) Slaughter, L. G. M. ACS Catal. 2012, 1802, 2; (b) Boyarskiy, V. P.; Luzyanin, K.
V.; Kukushkin, V. Yu. Coord. Chem. Rev. 2012, 256, 2029.
12. Dhudshia, B.; Thadani, A. N. Chem. Commun. 2006, 668.
3
C
6
H
2
95
90
b
6
H
4
-I
-I
1
1
3. Khaibulova, T. S.; Boyarskaya, I. A.; Boyarskii, V. P. Russ. J. Org. Chem. 2013, 49,
360.
4. Miltsov, S.; Karavan, V.; Boyarsky, V.; Gomez-de Pedro, S.; Alonso-Chamarro, J.;
Puyol, M. Tetrahedron Lett. 2013, 54, 1202.
6
H
4
96
98 (95 )
a
2
C
6
H
4
-I
4-MeOC
4-MeOC
4-MeOC
4-MeOC
4-MeOC
4-MeOC
6
6
6
6
6
6
H
H
H
H
H
H
4
4
4
4
4
4
-C„CH
94
94
90
10
11
12
13
14
15
16
17
18
19
20
21
22
H
6 4
-I
-C„CH
-C„CH
-C„CH
-C„CH
-C„CH
b
15. Ryabukhin, D. S.; Sorokoumov, V. N.; Savicheva, E. A.; Boyarskiy, V. P.; Balova, I.
2
C
6
H
3
-I
A.; Vasilyev, A. V. Tetrahedron Lett. 2013, 54, 2369.
2
C
6
H
4
-I
-I
98
98
95
89
85
97
80
98
96
2 2 2 2
16. PdCl {C(N(H)-NPh )@N(H)Cy}(C„NCy), complex II. PdCl (CyNC) (200 mg,
6
H
4
0.50 mmol) and 1,1-diphenylhydrazine (97 mg, 0.54 mmol) were dissolved in
6
H
4
-I
1,2-dichloroethane (10 mL) and refluxed at 84 °C for 4 h. The mixture was
n-C
n-C
n-C
6
6
6
H13-C„CH
H13-C„CH
H13-C„CH
cooled and n-hexane (30 mL) was added. The white precipitate was filtered
off, washed with Et
O (2 Â 30 mL) and dried under air. Yield 244 mg (85%).
H NMR (300 MHz, CDCl ): 10.34 s (1H, C@NHN), 7.29–7.35 m (8H, HAr),
6
H
4
-I
2
1
2
C
6
H
4
-I
3
Me
Me
Me
2
(HO)C-C„CH
(HO)C-C„CH
(HO)C-C„CH
7.08–7.14 m (3H, 2HAr + NH), 4.47–4.62 m (1H, CH), 3.98–4.05 m (1H, CH),
À1
6
H
4
-I
2
2
1.28–2.17 m (20H, 10CH
2
). IR (KBr, selected bands, cm ):
m
(C-H) 2933–
+
2830, (C„N) 2227, d (N-Ccarbene-N) 1560, m
m
(CAr–N) 1360. ESI -MS: found:
4
H34ClN Pd: 545.1490. Elemental analysis:
2
C
6
H
4
-I
-Br
-Br
+
c
545.1421 [MÀCl] ; calcd for C26
H
6 4
Ph-C„CH
Ph-C„CH
12
62
c
found, %: C 53.95; H 5.81; N 9.48; calcd for C26
H
34Cl
2 4
N Pd, %: C 53.81; H 5.90;
2
C
6
H
4
N 9.46.
a
b
c
Isolated yield on 20 mmol scale.19,20
Conversion of ArI was 94%.
17. Optimization of the reaction parameters.
A
vial was charged with 4-
iodotoluene (0.1 mmol), phenylacetylene (0.11 mmol), biphenyl (0.03 mmol,
internal standard), K CO (0.15 mmol) and EtOH (2 mL). Complex I or II (an
1
mol % of the catalyst was used.
2
3
aliquot of an ethanol solution) was added. The mixture was stirred for the
selected amount of time at room temperature or at reflux. The mixture was
2 2 2
cooled and CH Cl –n-hexane (1:2, 2 mL) and H O (2 mL) were added. The
organic layer was separated, filtered through a small amount of silica gel and
analyzed by GC.
8. General procedure for the coupling of aryl halides with terminal acetylenes. A
vial was charged with an aryl halide (0.1 mmol), an aryl or alkylacetylene
Acknowledgments
1
1
The authors thank the Russian Foundation for Basic Research
Grant 14-03-00297a) and St. Petersburg State University (Grant
(0.11 mmol), K
2 mL). The mixture was refluxed with stirring for 2 h. After this time, the
mixture was cooled and CH Cl –n-hexane (1:2, 2 mL) and H O (2 mL) were
2 3
CO (0.15 mmol), palladium catalyst (0.05 mol %), and EtOH
(
(
2
2
2
1
2.38.195.2014) for financial support of this work. NMR studies
added. The organic layer was separated, filtered through a small amount of
silica gel and analyzed by GC–MS. The solvent was removed and the residue
were performed at the Research Resources Center for Magnetic
Resonance of Saint Petersburg State University. GC and GC–MS
analyses were performed at the Educational Resource Center of
Chemistry of Saint-Petersburg State University.
1
weighed and analyzed by H NMR.
9. 1,2-Diphenylacetylene.8
c
A
100 mL round-bottom flask was charged with
CO (4.2 g,
iodobenzene (4.1 g, 20 mmol), phenylacetylene (2.2 g, 22 mmol), K
2
3
30 mmol), complex I (5.5 mg, 0.01 mmol), and EtOH (35 mL). The mixture was
refluxed with stirring for 2 h. After this time, the mixture was cooled and
2
diluted with H O. The organic compounds were extracted with n-hexane
References and notes
(
2 Â 50 mL), the solvent evaporated and the crude residue purified by column
chromatography (n-hexane) to afford 3.0 g of pure diphenylacetylene (84%,
1
2
3
4
5
.
.
.
.
.
Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 4467.
Chinchilla, R.; Najera, C. Chem. Soc. Rev. 2011, 40, 5084.
Pu, X.; Li, H.; Colacot, T. J. J. Org. Chem. 2013, 78, 568.
Glaser, C. Ber. Dtsch. Chem. Ges. 1869, 2, 422.
(a) Heravi, M. M.; Sadjadi, S. Tetrahedron 2009, 65, 7761; (b) Yoo, E. J.; Chang, S.
Org. Lett. 2008, 10, 342; (c) Dudnik, A. S.; Chernyak, N.; Gevorgyan, V.
Aldrichimica Acta 2010, 43, 37.
Beletskaya, I. P.; Kustov, L. M. Russ. Chem. Rev. 2010, 79, 441.
(a) Dieck, H. A.; Heck, F. R. J. Organomet. Chem. 1975, 93, 259; (b) Cassar, L. J.
Organomet. Chem. 1975, 93, 253.
white solid, mp = 60 °C).
20. 1-(4-Nitrophenyl)-2-phenylacetylene.8 A 100 mL round-bottom flask was
c
charged with 4-nitroiodobenzene (4.9 g, 20 mmol), phenylacetylene (2.2 g,
22 mmol), K CO3 (4.2 g, 30 mmol), complex
2
I (5.5 mg, 0.01 mmol), and
EtOH (35 mL). The mixture was refluxed with stirring for 2 h. After this
time, the mixture was cooled and diluted with H O. The organic
2
compounds were extracted with EtOAc (2 Â 50 mL). The solvent was
6
7
.
.
evaporated and the crude residue purified by recrystallization (MeOH) to
afford 4.2 g of pure 1-(4-nitrophenyl)-2-phenylacetylene (95%, yellow solid,
mp = 120 °C).