The [(E,E,E)-1,6,11-tris(p-toluenesulfonyl)-1,6,11-triazacyclopentadeca-3,8, 13-triene]Pd(0) complex in the hydroarylation of alkynes in ionic liquids. An approach to quinolines

Article abstract of DOI:10.1016/S0040-4039(02)01120-6

The hydroarylation of alkynes can be successfully conducted in 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF₄) in the presence of the [(E,E,E)-1,6,11-tris(p-toluenesulfonyl)-1,6,11-triazacyclopentadeca-3,8, 13-triene]Pd(0) complex. Th

Full text of DOI:10.1016/S0040-4039(02)01120-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5537–5540
The [(E,E,E)-1,6,11-tris(p-toluenesulfonyl)-1,6,11-
triazacyclopentadeca-3,8,13-triene]Pd(0) complex in the
hydroarylation of alkynes in ionic liquids.
An approach to quinolines
Sandro Cacchi,a,* Giancarlo Fabrizi,a Antonella Goggiamani,a Marcial Moreno-Man˜asb and
Adelina Vallriberab
aDipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Universita` degli Studi ‘‘La Sapienza’’,
P.le A. Moro 5, 00185 Rome, Italy
bDepartment of Chemistry, Universitat Auto`noma de Barcelona, Cerdanyola, 08193 Barcelona, Spain
Received 10 June 2002; accepted 13 June 2002
Abstract—The hydroarylation of alkynes can be successfully conducted in 1-butyl-3-methylimidazolium tetrafluoroborate
([bmim]BF4) in the presence of the [(E,E,E)-1,6,11-tris(p-toluenesulfonyl)-1,6,11-triazacyclopentadeca-3,8,13-triene]Pd(0) complex.
The catalytic ionic solution can be recycled for reuse in subsequent reaction runs. The procedure has been applied to the
preparation of 3-arylquinolines through a domino hydroarylation/cyclization process. © 2002 Elsevier Science Ltd. All rights
reserved.
The employment of room temperature ionic liquids in
synthesis is emerging as an attractive alternative to that
of classical molecular organic solvents. Some of their
properties (no detectable vapor pressure, possible recy-
cling, easy separation from the products, thermal
robustness) make them promising candidates for the
development of environmentally friendly synthetic
methodologies. To date, a variety of reactions have
been successfully carried out in these solvents,1 and
many of them describe the utilization of palladium
catalysis,2 thus establishing the feasibility of homo-
geneous palladium-catalyzed reactions in ionic liquids.
Here we wish to report that the palladium-catalyzed
hydroarylation of alkynes can be conducted in 1-butyl-
3-methylimidazolium tetrafluoroborate ([bmim]BF4),10
a room temperature ionic liquid reported to be virtually
insoluble in alkanes and diethyl ether but to dissolve
many organic and organometallic compounds, in the
presence of the [(E,E,E)-1,6,11-tris(p-toluenesulfonyl)-
1,6,11-triazacyclopentadeca-3,8,13-triene]Pd(0)
com-
plex11 (Scheme 1); the catalyst/ionic liquid system can
be successfully reused in subsequent reaction runs.12,13
Initial attempts were made subjecting p-iodoanisole to
diphenylacetylene in the presence of triethylamine, for-
Our
palladium-catalyzed
hydroarylation
and
hydrovinylation reaction represents a useful tool for
organic synthesis. The reaction has been examined with
a,b-unsaturated carbonyl compounds,3 norbornene
derivatives,4 and alkynes.5 Sequential hydroarylation
(hydrovinylation)/cyclization processes have been devel-
oped into new approaches to functionalized
butenolides,6 quinolines7 and chromenes.8 Intramolecu-
lar versions of the reactions have also been described.9
Pd(0)L
HCOOH
Et3N
Ar
Ph
Ph
ArI
[bmim]BF4
80 °C
Ph
Ph
3
1
2
NTs
Keywords: hydroarylation; palladium; macrocyclic ligands; ionic liq-
uids; quinolines.
L = TsN
NTs
* Corresponding author. Fax: +39 (06) 4991-2780; e-mail:
sandro.cacchi@uniroma1.it
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01120-6

5538
S. Cacchi et al. / Tetrahedron Letters 43 (2002) 5537–5540
mic acid and classical Pd(0) donors such as Pd(PPh3)4
or Pd2(dba)3 at 80°C for 8 h. With Pd(PPh3)4 the
desired hydroarylation derivative was isolated only in
41% yield. Employing Pd2(dba)3 increased the yield up
to 82%, but a significant drop was observed on the first
recharge (59% yield). Switching to [(E,E,E)-1,6,11-
tris(p-toluenesulfonyl)-1,6,11-triazacyclopentadeca-3,8,
13-triene]Pd(0) produced the corresponding hydroaryla-
tion product in 89% yield (comparable to the 92% yield
obtained with the same catalyst system in DMF) and,
what is more, allowed an extensive recycling of the
ionic catalyst solution (vide infra). Keeping all the other
parameters the same but substituting 1-butyl-3-
methylimidazolium hexafluorophosphate ([bmim]PF6)
for [bmim]BF4 produced the hydroarylation product in
41% yield, and the yield on the first recharge was only
25%. Therefore, [bmim]BF4 was used as the solvent
when the procedure was extended to include other aryl
iodides. The unoptimized yields and stereoselectivity
were usually satisfactory (Table 1).
as the model reaction. The reaction (Scheme 2) pro-
ceeds in a straightforward fashion, producing quinoline
derivatives in good overall yield and satisfactory
regioselectivity. The new carbon–carbon bond is
formed preferentially at the carbon bearing the acetal
group and 3-arylquinolines 6 were isolated as the main
products (Table 2).
One of the main tasks of this research effort was to
develop an efficient procedure for recycling the catalyst/
ionic liquid system. Therefore, we investigated the num-
ber of times that we could reuse the ionic catalytic
solution by employing the reaction of diphenylacetylene
with p-iodoanisole and ethyl p-iodobenzoate, models of
electron-donating and electron-withdrawing aryl
iodides. As shown in Table 3, the solution containing
the catalytically active palladium species can be used at
least six times with essentially no loss of activity with
p-iodoanisole and only a modest decrease in activity
with ethyl p-iodobenzoate.
The extension of the procedure to develop a domino
hydroarylation/cyclization process was also investigated
and the formation of substituted quinolines from 3,3-
die-1-phenyl-1-propyne 5 and aryl iodides was chosen
OEt
OEt
ArI
NHAc
5
2
Pd(0)L
HCOOH, Et3N
[bmim]BF4
60 °C
Table 1. The hydroarylation of diphenylacetylene in
[bmim]BF4 in the presence of [(E,E,E)-1,6,11-tris(p-toluene-
sulfonyl)-1,6,11-triazacyclopentadeca-3,8,13-triene]Pd(0)a
Ar
Ar
Entry
Aryl iodide 2
Reaction
time (h)
3 yield%b
E:Zc
N
N
6
7
1
2
3
4
5
6
7
8
p-MeO-C6H4-I
m-MeOC6H4-I
p-F-C6H4-I
p-MeCO-C6H4-I
p-EtOOC-C6H4-I
p-EtOOC-C6H4-I
m-EtOOC-C6H4-I
8
60
480
24
24
24
89d
59d
45
94:6
95:5
\99:1
\99:1
91:9
91:9
94:6
Scheme 2.
Table 3. Recycling studies for the reaction of Scheme 1
36
77
69d
70
48
Number of
cycles
Yield% (with
p-iodoanisole)
Yield% (with ethyl
p-iodobenzoate)
2-NO2-4-Me-C6H3-I 79
35
88:12
a Unless otherwise stated, reactions were carried out at 80°C using the
following molar ratios: 1:2:Et3N:HCOOH:[Pd]=1:2:2:1.5:0.02.
b Yields refer to single runs and are given for isolated products. All
products had satisfactory elemental analyses, and their spectra were
consistent with the postulated structures.
1st
89
89
85
74
70
86
77
83
72
72
69
58
2nd
3rd
4th
5th
6th
c Calculated by NMR analysis.
d 1:2:Et3N:HCOOH:[Pd]=1:1.5:2:1.5:0.02.
Table 2. Synthesis of 3-arylquinolines in the presence of [(E,E,E)-1,6,11-tris(p-toluenesulfonyl)-1,6,11-triazacyclopentadeca-
3,8,13-triene]Pd(0)a
Entry
Aryl iodide 2
Reaction time (d)
Yield% of 6b
Yield% of 7b
6/7
1
2
3
4
p-MeO-C6H4-I
p-Me-C6H4-I
p-F-C6H4-I
6
3
3
3
56
67
67
74
9
12
13
21
86:14
85:15
84:16
79:21
p-EtOOC-C6H4-I
a Reactions were carried out at 60°C using the following molar ratios: 1:2:Et3N:HCOOH:[Pd]=1:2.4:3:2:0.025.
b Yields refer to single runs and are given for isolated products. All products had satisfactory elemental analyses, and their spectra were consistent
with the postulated structures.

S. Cacchi et al. / Tetrahedron Letters 43 (2002) 5537–5540
5539
In summary, we have demonstrated that the [(E,E,E)-
1,6,11-tris(p-toluenesulfonyl)-1,6,11-triazacyclopenta-
deca-3,8,13-triene]Pd(0) complex can be successfully
employed for the hydroarylation of alkynes in 1-butyl-
3-methylimidazolium tetrafluoroborate ([bmim]BF4)
and that the palladium-containing catalytically active
species, ‘‘immobilized’’ in the ionic liquid, can be reused
for subsequent runs with little loss in activity.
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Acknowledgements
Work carried out in the framework of the National
Project ‘‘Stereoselezione in Sintesi Organica. Metodolo-
gie ed Applicazioni’’ supported by the Ministero dell’U-
niversita` e della Ricerca Scientifica e Tecnologica,
Rome. Financial support of this research by the Uni-
versity ‘‘La Sapienza’’, Rome, is also gratefully
acknowledged. Spanish partners acknowledge financial
support from MEC (project PB98-0902) and Generali-
tat de Catalunya (project 2001-SGR0181). This work
has been possible thanks to project COST D12/0011/98.
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S. Cacchi et al. / Tetrahedron Letters 43 (2002) 5537–5540
10. 1-Butyl-3-methylimidazolium tetrafluoroborate ([bmim]-
BF4) was prepared according to Ref. 2l.
assigned on the basis of our previous work that shows a
general predominance of cis addition products following
the carbopalladation step: (E)-isomer: oil; IR (neat):
2940, 1606, 1077 cm−1; 1H NMR (CDCl3) l 7.37–7.05 (m,
12H), 6.92–6.85 (m, 3H), 3.84 (s, 1H); 13C NMR (CDCl3)
l 159.2, 142.1, 140.6, 137.6, 136.1, 130.4, 129.5, 129.4,
128.8, 127.9, 127.3, 126.5, 126.4, 113.6, 55.3; Anal calcd
for C21H18O: C, 88.08; H, 6.34; Found: C, 88.17; H, 6.39;
11. (a) Corte`s, J.; Moreno-Man˜as, M.; Pleixats, R. Eur. J.
Org. Chem. 2000, 239–243; (b) Cerezo, S.; Corte`s, J.;
Lago, E.; Molins, E.; Moreno-Man˜as, M.; Parella, T.;
Pleixats, R.; Torrejo´n, J.; Vallribera, A. Eur. J. Inorg.
Chem. 2001, 1999–2006.
12. Typical procedure for the hydroarylation of alkynes: To a
50 mL carousel reaction tube (Radley Discovery Technol-
(Z)-isomer: oil; IR (neat): 2941, 1608, 1080 cm−1 1H
;
ogy) containing
a magnetic stir bar were added
NMR (CDCl3) l 7.38–7.0 (m, 12H), 6.92–6.83 (m, 3H),
3.85 (s, 3H); 13C NMR (CDCl3) l 158.9, 143.8, 142. 2,
137.6, 132.5, 131.6, 1128.6, 128.1, 128.0, 127.8, 127.7,
127.5, 126.6, 114.0, 55.2; Anal calcd for C21H18O: C,
88.08; H, 6.34; Found: C, 88.19; H, 6.35. Recycling of the
catalyst/ionic liquid system: After completion of the
diethyl ether washes, diphenylacetylene (89.0 mg, 0.50
mmol), p-iodoanisole (175.0 mg, 0.75 mmol), triethyl-
amine (139 mL, 1.00 mmol) and formic acid (30 mL, 0.75
mmol) were added to the ionic catalytic solution. The
reaction mixture was stirred at 80°C for 8 h. After this
time, the mixture was worked-up as before.
[bmim]BF4 (2 mL) and [(E,E,E)-1,6,11-tris(p-toluenesul-
fonyl)-1,6,11-triazacyclopentadeca-3,8,13-triene]Pd(0) (7.7
mg, 0.01 mmol). The mixture was stirred at 80°C for 1 h
under argon. Then, diphenylacetylene (89.0 mg, 0.50
mmol), 4-iodoanisole (175.0 mg, 0.75 mmol), triethyl-
amine (139 mL, 1.00 mmol) and formic acid (30 mL, 0.75
mmol) were added. The solution was stirred at 80°C for
8 h. After this time, the reaction mixture was cooled to
room temperature and washed with diethyl ether (15
mL×5 times). The organic extracts were then combined,
washed with water, dried over NaSO4 and concentrated
under reduced pressure. The residue was purified by
chromatography on silica gel [n-hexane/ethylacetate 95/5
(v/v)] to give 0.126 mg (89% yield) of 1,2-diphenyl-1-(p-
methoxyphenyl)ethylene as an approximately E:Z 96:4
stereoisomeric mixture. The two stereoisomers were sepa-
rated by preparative HPLC and their configuration
(NOE experiments did not provide clear-cut results) was
13. For use and recycle of a related [(E,E,E)-1,6,11-tris(are-
nesulfonyl)-1,6,11-triazacyclopentadeca-3,8,13-triene]Pd-
(0) in butadiene telomerization see: Estrine, B.; Blanco,
B.; Bouquillon, S.; He´nin, F.; Moreno-Man˜as, M.;
Muzart, J.; Pena, C.; Pleixats, R. Tetrahedron Lett. 2001,
42, 7055–7057.