Task specific onium salts and ionic liquids as soluble supports in Grieco's multicomponent synthesis of tetrahydroquinolines

Article abstract of DOI:10.1007/s00706-007-0708-0

In this work was presented an application of the use of task specific onium salts (TSOSs) as soluble supports in Grieco's multicomponent synthesis of tetrahydroquinolines. These soluble supports are of wide applicability and combine advantages of solid ph

Full text of DOI:10.1007/s00706-007-0708-0

Monatshefte fu¨r Chemie 138, 1167–1174 (2007)
DOI 10.1007/s00706-007-0708-0
Printed in The Netherlands
Task Specific Onium Salts and Ionic Liquids as Soluble Supports
in Grieco’s Multicomponent Synthesis of Tetrahydroquinolines
ꢀ
Fatima Hassine, Said Gmouh, Mathieu Pucheault, and Michel Vaultier
´
Universite de Rennes 1, UMR CNRS 6510, Campus de Beaulieu, Rennes Cedex, France
Received April 13, 2007; accepted (revised) May 8, 2007; published online October 27, 2007
# Springer-Verlag 2007
Summary. In this work was presented an application of the
ports have been developed based on dendrimeric
use of task specific onium salts (TSOSs) as soluble supports in
Grieco’s multicomponent synthesis of tetrahydroquinolines.
These soluble supports are of wide applicability and combine
advantages of solid phase synthesis without its limitations
with those of solution phase chemistry. After a simple washing
step, products were cleaved from the supports and obtained in
pure form and good yields.
alcohols [3], polyethylene glycols (PEGs), or soluble
polystyrenes (JandaJels) to mention the most impor-
tant ones [4–6]. They allowed for recovering liquid
phase properties by fine tuning of solvent conditions
and linker structures. PEGs have for example been
used successfully in the synthesis of peptides [7], oli-
gosaccharides [8], oligonucleotides [9], and small mo-
lecules. However, once again, low loading capacity,
water solubility, and impurities co-precipitation dur-
ing the purification have narrowed their applicability.
Recently, a valuable alternative to these supports
has been proposed based on specificities of room
temperature ionic liquids (RTILs) [10]. Introducing
a specific functionality into RTILs led to the so-
called task specific ionic liquids (TSILs), which
could serve as reagents, reactants, catalysts, or solu-
ble supports for organic synthesis [11–14]. Task
specific onium salts were an extension of the above
concept to salts having a melting point over 100ꢁC
[15]. We and others have used them successfully for
peptide synthesis [16], transition metal catalyzed re-
actions [17] and multi component reactions (MCR)
(Fig. 1) [18, 19]. Non-supported versions of multi-
component reactions were often handicapped by side
reactions leading to separation difficulties. Indeed,
by supporting one reactant and therefore getting sup-
ported products, purification and removal of traces of
impurities would be largely improved, but examples
were scarce due to kinetic limitations in heteroge-
neous medium [20–22].
Keywords. Heterocycles; Solution phase synthesis; Multi-
component reactions; Acid catalysis; Functionalized ammo-
nium salts.
Introduction
In the last decades solid phase organic synthesis
(SPOS) has undoubtedly been the method of choice
for rapidly preparing ensembles of small molecules.
By supporting a reagent on a resin or a polymer,
purification was shortened to simple filtrations; di-
versity was enhanced by split and mix methods and
high throughput parallel synthesis could be realized
[1, 2]. However, some limitations were remaining,
inherent to the heterogeneous nature of mixtures.
In addition to high prices and low loading capacities,
resins were inducing slow and non-linear kinetics
due to poor diffusion and difficulties to access active
sites. Often, analysis happened to be tricky and ne-
cessitated special technology such as HR MAS
NMR. To circumvent these problems, soluble sup-
ꢀ
rennes1.fr
Corresponding author. E-mail: michel.vaultier@univ-

1168
F. Hassine et al.
yields [23]. Mild catalytic conditions (often using
lanthanide triflates) [24], could be used and were
compatible with a wide range of aldehydes and ani-
lines, therefore easily providing tetrahydroquinolines
with large diversity.
Fig. 1. Onium salts supported synthesis (OSSS) applied to
multicomponent reactions
In our case, we decided to support on onium salts
two of the three possible partners, namely the aniline
and the benzaldehyde. Starting from trimethyl-3-hy-
droxypropylammonium chloride (1) both supported
reagents were prepared in few high yielding steps.
Supported aniline was synthesized by coupling
4-nitrobenzoic acid with alcohol 1 followed by hy-
drogenative reduction of 2a into the aniline. If nec-
essary, preparation of the triflimide onium salts was
achieved by ion metathesis with lithium triflimide in
water providing aniline 3 in 83% overall yield (3
steps). Similarly, aldehyde 2b was prepared by sim-
ply coupling of 4-formylbenzoic acid with alcohol
1 under standard conditions. Tetrafluoroborate salt
4 was subsequently obtained by simple treatment
with aqueous tetrafluoroboric acid in 90% yield after
2 steps.
Here, we report our results concerning multicom-
ponent reactions involving a task specific onium salts
synthesis strategy. After design and preparation of
task specific onium salts with suitable functionality,
they were separately engaged in a Grieco reaction
with two other partners. An easy purification by sim-
ple washings followed by cleavage from support pro-
vided Grieco quinolines in excellent yields.
Results and Discussion
Substrates Synthesis
Grieco synthesis is a single pot multicomponent
reaction between anilines, aldehydes, and electron-
rich alkenes providing tetrahydroquinolines in high
Scheme 1

Task Specific Onium Salts
1169
Scheme 2
Table 1. Grieco’s reaction using onium salt supported aniline
Entry
X
Olefin
Solvent
Time=h
Product
Conv=%a
(Yield=%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
H 5a
H 5a
H 5a
NO2 5b
Cl 5c
Br 5d
OMe 5e
NO2 5b
Cl 5c
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6b
6b
6c
6c
[tmba][NTf2]
[HO(CH2)3NMe3][NTf2]
CH3CN
0.5
0.5
0.4
0.5
0.5
0.5
0.5
0.4
0.4
0.4
1.25
0.5
0.5
0.75
0.75
7aa
7aa
7aa
7ba
7ca
7da
7ea
7ba
7ca
7da
7ea
7bb
7db
7bc
7dc
100 (77)c
100
100 (70)
100 (90)c
100
100 (88)c
100
100 (93)
100 (89)
100 (90)
100 (67)
100 (85)
100 (83)
100 (79)
100 (86)
[tmba][NTf2]
[tmba][NTf2]
[tmba][NTf2]
[tmba][NTf2]
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Br 5d
OMe 5e
NO2 5b
Br 5d
NO2 5b
Br 5d
a
1
Measured by H NMR isolated yield after purification isolated after cleavage from support
b
c
Use of Supported Aniline in the Grieco Reaction
(entries 8–15). To our delight, most benzaldehydes
(entries 4–6) were highly reactive (100% conversion
after 30 min) with cyclopentadiene 6a and supported
aniline. For example, condensation with 4-nitroben-
zaldehyde (entry 4), 4-bromobenzaldehyde (entry
5), and 4-chlorobenzaldehyde (entry 6) proceeds
smoothly affording supported tetrahydroquinolines
in 30 min. Reaction was slightly slower using benz-
aldehyde bearing electron-donating groups, although
82% conversion was obtained after 75 min in the
case of 4-methoxybenzaldehyde (entry 7). In aceto-
nitrile, similarly to [tmba][NTf2] most reactions
We decided next to tackle the core of the project by
engaging supported aniline in the Grieco reaction with
an aldehyde and an electron-rich olefin. Several sol-
vents were investigated in the presence of a catalytic
amount of trifluoroacetic acid. The reaction was found
to be efficient in both molecular solvents like acetoni-
trile and ionic liquids, such as [tmba][NTf2] (trimethyl-
butylammonium triflimide) (Table 1, entries 1–3).
Reaction applicability was investigated simulta-
neously in [tmba][NTf2] (entries 4–7) and acetonitrile

1170
F. Hassine et al.
Scheme 3
appeared to be quantitative after a short 20 min reac-
tion time. With 4-nitro (entry 8), 4-chloro (entry 9),
and 4-bromobenzaldehyde (entry 10), the reaction
was efficiently leading to expected products in good
to excellent yields. Using electron rich 4-methoxy-
benzaldehyde (entry 11), like previously mentioned,
reaction was slower albeit affording the expected
product in a good 67% yield after 75 min. Other
olefins were used, such as indene (6b) or styrene
(6c). With respects to the olefin, tetrahydroquino-
lines were equally obtained in less than an hour in
good yields (entries 12–15). In all cases, the pro-
ducts were purified by filtration followed by washing
with Et2O, which eliminates unreacted reagents and
eventual non-supported side products. This proce-
dure simplifies to a large extent previously reported
methodologies for multicomponent reactions in ho-
mogeneous phase as no complicated purification was
needed. Moreover, reactions could be easily moni-
titative conversions were obtained using both cyclo-
pentadiene (6a) (entry 1) and indene (6b) (entry 4).
Various anilines 8 were tested, bearing nitro (entry 2)
or bromide (entry 3) subtituents affording tetrahy-
droquinolines in good yields.
Like previously mentioned, products 9 were puri-
fied after reaction by simple filtration followed by
washing with Et2O. Concerning cleavage from the
support, simple treatment by NH3 in methanol af-
forded methyl ester 10aa in good yield.
Onium salts supported organic synthesis turned out
to be particularly suitable in the Grieco multicompo-
nent reaction. A wide variety of tetrahydroquinolines
were obtained with quantitative conversion in a short
Table 2. Grieco’s reaction using onium salt supported benz-
aldehyde
Entry Aniline Olefin Time= Product Conv= Yield=
h
a
%
b
%
1
tored by H NMR unlike the solid phase synthesis.
1
2
3
4
8a
8b
8c
8c
6a
6a
6a
6b
2
2
2
2
9aa
9ba
9ca
9cb
100
100
100
100
77
90
88
92
Use of Supported Benzaldehyde in Grieco Reaction
Similarly, supported benzaldehyde 4 was engaged
under the same reaction conditions. After 2 h, quan-
Measured by NMR 1H b isolated yield after purification
a
Scheme 4

Task Specific Onium Salts
1171
(200MHz, D2O): ꢁ ¼ 2.10–2.25 (m, 2H), 3.09 (s, 9H), 3.32–
3.45 (m, 2H), 4.48 (t, 2H, J ¼ 6.1 Hz), 6.75 (d, 2H,
J ¼ 7.8Hz), 7.72 (d, 2H, J ¼ 7.8 Hz) ppm; 13C NMR
(50 MHz, D2O): ꢁ ¼ 22.6, 53.47 (t, JC–N ¼ 4.1 Hz), 61.9,
64.2, 114.9, 118.2, 132.0, 153.0, 168.8 ppm; HRMS (FAB)
C13H21N2O2: calcd. 237.1603, found 237.1603. To an aque-
ous solution (300 cm3) of this solid (6.95 g) was added an
aqueous solution of lithium bistrifluoromethanesulfonamide
(1.1equ.) in 300 cm3. After 2 h at room temperature, the mix-
ture was extracted with 3ꢂ200 cm3 CH2Cl2. Organic phases
were assembled, dried over Na2SO4, and after filtration and
concentration under reduced pressure, 20.5g of a white pow-
der were obtained. Yield 93%; mp 109–110ꢁC; 1H NMR
(200MHz, Acetone-d6): ꢁ ¼ 2.35–2.51 (m, 2H), 3.41 (s, 9H),
3.78–3.92 (m, 2H), 4.50 (t, 2H, J ¼ 6.1 Hz), 5.51 (br, 2H),
6.58 (d, 2H, J ¼ 7.9 Hz), 7.84 (d, 2H, J ¼ 7.7Hz) ppm; 13C
NMR (50 MHz, Acetone-d6): ꢁ ¼ 24.2, 54.1 (t, JC–N ¼ 4.1 Hz),
61.7, 65.6, 114.2, 118.3, 121.2 (q, JC–F ¼ 320Hz), 132.7,
154.7, 167.1 ppm; HRMS (FAB) C28H42F6N5O8S2: calcd.
754.2379, found 754.2379.
period of time. We showed that supporting both ani-
lines and aldehydes could be envisioned in this strat-
egy. Both supports synthesis turned out to be high
yielding, and only simple workup (filtration and
wash) was needed to obtain a good purity.
Furthermore, unlike traditional solid phase support-
ed versions of this reaction, kinetics were increased
and no large excess of reagent was needed to drive
the reaction to completion.
Experimental
General Methods
All reactions were carried out using standard Schlenk tech-
niques under argon. Acetonitrile and ether were carefully dried
and distilled prior to use. All other standard chemicals were
purchased from ACROS Chimica or Aldrich Chemical Co.,
and used without further purification. Reactions were moni-
tored by gas chromatography (GC-MS) (GC system: HP 6890
series, mass selective detector HP 5973) using a capillary
column DB-5MS. Column chromatography purifications were
performed on silica gel Si 60 (40–63ꢀm, 230–400 mesh,
Merck). Melting points were determined on an electrothermal
IA9300 digital melting point instrument. NMR spectra were
recorded on a Bruker ARX 200 (1H: 200.13 MHz, 13C:
50.32 MHz) or AC 300 (1H: 300.13 MHz), 1H chemical shifts
(ꢁ) are given in ppm relative to TMS as internal standard, J
values in Hz; 13C chemical shifts are given relative to the
central signal of CDCl3 at 77.0ppm. High resolution mass
spectra measurements were performed at the Centre Regional
de Mesures Physiques de l’Ouest (C. R. M. P. O., University of
Rennes 1) using a Micromass ZABSpec TOF with EBE OA
TOF geometry with LSIMS Ionization (Liquid Secondary Ion
Mass Spectrometry) at 8 kV with Csþ gun in m-nitrobenzyl
alcohol (mNBA).
[3-(4-Formylbenzoyloxy)propyl]trimethylammonium
tetrafluoroborate (4, C14H20NO3BF4)
To a solution of 2 g 1 (13 mmol) in 100 cm3 CH3CN
were added DCC (19.5 mmol, 1.5 equ.), 4-formylbenzoic
acid (19.5 mmol, 1.5 equ.) and DMAP (2.6 mmol, 0.2 equ.).
After 2 h at room temperature, solvent was removed and
the residue was extracted with 3ꢂ30 cm3 H2O. To this
solution was added a 50% aqueous solution of HBF4
(19.5 mmol, 1.5 equ.) and after 2 h at room temperature,
a yellow precipitate formed. The suspension was filtered
and yellow crystals were washed with 20 cm3 H2O then
2ꢂ20 cm3 Et2O to afford 2.92 g of a pale yellow solid.
1
Yield 90%; mp 146–148ꢁC; H NMR (200 MHz, CD3CN):
ꢁ ¼ 2.10–2.33 (m, 2H), 3.05 (s, 9H), 3.36–3.55 (m, 2H),
4.45 (t, 2H, J ¼ 5.8 Hz), 8.00 (dd, 2H, J ¼ 1.6, 6.6 Hz),
8.13 (dd, 2H, J ¼ 1.4, 8.3 Hz), 10.10 (s, 1H) ppm; 13C
NMR (50 MHz, CD3CN): ꢁ ¼ 22.1, 52.7 (t, J ¼ 3.8 Hz),
61.5, 63.5 (t, J ¼ 3.0 Hz), 129.1, 129.8, 134.4, 139.3,
164.9, 192.0 ppm; MS (APCI) m=z ¼ 250.3 (Cþ).
[3-(4-Aminobenzoyloxy)propyl]trimethylammonium
bistrifluoromethanesulfonamide (3, C28H42F6N5O8S2)
To a mixture of 5.00 g alcohol 1 (32.57 mmol) in 100 cm3
dry acetonitrile were added DCC (48.5 mmol, 1.5 equ.),
4-nitrobenzoic acid (48.5 mmol, 1.5 equ.), and DMAP
(6.52 mmol, 0.2 equ.). After 4 h at room temperature, solvents
were removed under vacuum and product was extracted with
3ꢂ30 cm3 Et2O to afford an oil used without further purif-
ication in the next step. 1H NMR (200MHz, D2O): ꢁ ¼ 2.18–
2.43 (m, 2H), 3.15 (s, 9H), 3.38–3.60 (m, 2H), 4.43 (t, 2H,
J ¼ 5.8 Hz), 8.02 (dd, 2H, J1 ¼ 1.9 Hz, J2 ¼ 7.1 Hz), 8.18 (dd,
2H, J1 ¼ 2.1 Hz, J2 ¼ 6.9 Hz) ppm; 13C NMR (50 MHz, D2O):
ꢁ ¼ 22.6, 53.5 (t, JC–N ¼ 4.0 Hz), 63.4, 64.1, 123.8, 130.9,
134.94, 150.3, 166.0 ppm. A solution of 2a (8.5g) in 100cm3
water with Pd=C (1%, 5% on C) was stirred under hydro-
gen atmosphere (5 bar) for 48 h. After filtration and concen-
tration under reduced pressure, 6.95g of a white solid were
obtained (90% yield, two steps) corresponding to N,N,N-
trimethyl-N-3-(4-nitrobenzoyloxypropyl)ammonium chloride
General Procedure for Grieco Condensation with Supported
Aniline 3 (Procedure A)
To a solution of amine 3 (100mg) in 2 cm3 CH3CN were
successively added aldehyde (1.1equ.), olefin (10 equ.), and
TFA (1.2equ.). After 2 h at room temperature, volatiles were
removed under reduced pressure. Upon addition of Et2O, the
residue crystallized. Crystals were filtered off and washed with
3ꢂ2 cm3 Et2O to afford product in pure form.
General Procedure for Grieco Condensation with Supported
benzaldehyde 4 (Procedure B)
To a solution of aldehyde 4 (100mg) in 2 cm3 CH3CN were
successively added aniline (1.1equ.), olefin (10 equ.), and TFA
(1.2equ.). After 2 h at room temperature, solvent was removed
under reduced pressure. Upon addition of Et2O, the resi-
due crystallized. Crystals were filtered off and washed with
3ꢂ2 cm3 Et2O to afford product in pure form.
1
13
1
as shown by H and C NMR. Mp 120–122ꢁC; H NMR

1172
F. Hassine et al.
4.42 (t, 2H, J ¼ 5.8 Hz), 4.90–5.00 (m, 1H), 5.58–5.65 (m,
1H), 5.70–5.80 (m, 1H), 5.93–6.05 (m, 1H), 6.85 (d, 1H,
J ¼ 8.4Hz), 7.30–7.70 (m, 6H) ppm; 13C NMR (50 MHz,
acetone-d6): ꢁ ¼ 24.2, 32.6, 46.7, 46.9, 54.2 (t, JC–N ¼ 4.0 Hz),
57.5, 61.9, 65.5, 116.5, 120.4, 121.4 (q, JC–F ¼ 321 Hz), 121.6,
125.9, 129.4, 129.9, 131.1, 132.3, 132.6, 135.6, 143.0, 152.2,
167.1 ppm; MS (APCI): m=z ¼ 470.1 (Cþ).
{3-[4-Phenyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]-
quinoline-8-carbonyloxy]propyl}trimethylammonium
bistrifluoromethanesulfonamide (7aa, C29H35F6N3O6S2)
Following procedure A using benzaldehyde 5a and cyclopen-
tadiene 6a provided expected product 7aa as a solid in 70%
1
yield; mp 118–120ꢁC; H NMR (300 MHz, acetone-d6): ꢁ ¼
1.65–1.84 (m, 1H), 2.38–2.64 (m, 3H), 2.96–3.15 (m, 1H),
3.45 (s, 9H), 3.73–3.90 (m, 2H), 4.10–4.22 (m, 1H), 4.42 (t,
2H, J ¼ 5.8 Hz), 4.70–4.80 (m, 1H), 5.58–5.65 (m, 1H), 5.70–
5.80 (m, 1H), 5.93–6.05 (m, 1H), 6.85 (d, 1H, J ¼ 8.4 Hz),
7.25–7.75 (m, 7H) ppm; 13C NMR (50 MHz, acetone-d6):
ꢁ ¼ 24.2, 32.7, 46.8, 47.2, 54.2 (t, JC–N ¼ 3.9 Hz), 58.1, 61.9,
65.6, 116.4, 120.2, 121.4 (q, JC–F ¼ 321 Hz), 126.0, 127.8,
128.4, 129.4, 129.6, 131.2, 132.3, 135.6, 143.5, 152.5,
167.1ppm; MS (APCI): m=z ¼ 391.4 (Cþ).
{3-[4-(Methoxyphenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta-
[c]quinoline-8-carbonyloxy]propyl}trimethylammonium
bistrifluoromethanesulfonamide (7ea, C30H37F6N3O7S2)
Following procedure A using 4-methoxybenzaldehyde 5e and
cyclopentadiene 6a provided expected product 7ea as a yel-
1
lowish solid in 67% yield. H NMR (300MHz, acetone-d6):
ꢁ ¼ 1.60–1.78 (m, 1H), 2.32–2.54 (m, 3H), 2.93–3.14 (m, 1H),
3.38 (s, 9H), 3.64–3.74 (m, 2H), 3.85(s, 3H), 4.01–4.11 (m,
1H), 4.17 (t, 2H, J ¼ 5.8 Hz), 4.58 (s, 1H), 5.51–5.61 (m,
1H), 5.69–5.77 (m, 1H), 5.82–5.88 (m, 1H), 6.87 (d, 1H,
J ¼ 8.3Hz), 7.42 (d, 2H, J ¼ 8.5 Hz), 7.51 (d, 2H, J ¼ 8.5 Hz),
{3-[4-(Nitrophenyl)-3a, 4, 5, 9b-tetrahydro-3H-cyclopenta-
[c]quinoline-8-carbonyloxy]propyl}trimethylammonium
bistrifluoromethanesulfonamide (7ba, C29H34F6N4O8S2)
Following procedure A using 4-nitrobenzaldehyde 5b and
cyclopentadiene 6a provided expected product 7ba as a solid
7.63 (dd, 1H, J1 ¼ 1.4 Hz, J2 ¼ 8.3 Hz), 7.73 (s, 1H) ppm; 13
C
NMR (300 MHz, acetone-d6) : ꢁ ¼ 22.1, 38.3, 45.3, 45.8, 53.1
(t, JC–N ¼ 4 Hz), 55.0, 56.3, 61.7, 63.7, 114.8, 118.3, 121.2,
121.4 (q, JC–F ¼ 321 Hz), 124.5, 127.8, 128.0, 128.1, 129.6,
130.8, 132.4, 133.9, 148.9, 158.1, 165.5ppm; MS (APCI):
m=z ¼ 421.2 (Cþ).
1
in 93% yield; mp 132–134ꢁC; H NMR (300 MHz, acetone-
d6): ꢁ ¼ 1.55–1.80 (m, 1H), 2.35–2.58 (m, 3H), 3.01–3.20 (m,
1H), 3.40 (s, 9H), 3.70–3.90 (m, 2H), 4.10–4.22 (m, 1H),
4.42 (t, 2H, J ¼ 5.8 Hz), 4.90–5.00 (m, 1H), 5.58–5.65 (m,
1H), 5.70–5.80 (m, 1H), 5.93–6.05 (m, 1H), 6.90 (d, 1H,
J ¼ 8.6 Hz), 7.60–7.95 (m, 4H), 8.28 (d, 2H, J ¼ 8.6 Hz)
ppm; 13C NMR (50 MHz, acetone-d6): ꢁ ¼ 24.2, 32.5, 46.6,
46.7, 54.2 (t, JC–N ¼ 4.0 Hz), 57.7, 62.0, 65.4, 116.7, 120.1 (q,
JC–F ¼ 321 Hz), 120.7, 124.7, 126.0, 129.0, 129.4, 131.0,
132.3, 135.5, 148.5, 151.4, 151.8, 167.0 ppm; MS (APCI):
m=z ¼ 436.1 (Cþ).
{3-[6-(4-Nitrophenyl)-5,6a,7,11b-tetrahydro-6H-indeno-
[2,1-c]quinoline-2-carbonyloxy]propyl}trimethylammonium
bistrifluoromethanesulfonamide (7bb, C33H36F6N4O8S2)
Following procedure A using 4-nitrobenzaldehyde 5b and
indene 6b provided expected product 7bb as a solid in 85%
1
yield; mp 122–124ꢁC; H NMR (300MHz, acetone-d6): ꢁ ¼
2.23–2.38 (m, 1H), 2.40–2.54 (m, 2H), 3.05–3.38 (m, 2H),
3.45 (s, 9H), 3.78–3.90 (m, 2H), 4.30–4.54 (m, 2H), 4.60
(d, 1H, J ¼ 7.5Hz), 5.04–5.12 (m, 1H), 6.15–6.20 (m, 1H),
6.83 (d, 1H, J ¼ 8.3 Hz), 7.02–7.13 (m, 3H), 7.60–7.70 (m,
2H), 7.85 (d, 2H, J ¼ 9.1 Hz), 7.95–8.01 (m, 1H), 8.30 (d, 2H,
J ¼ 9.1Hz) ppm; 13C NMR (50 MHz, acetone-d6): ꢁ ¼ 24.2,
32.1, 46.7, 48.5, 54.2 (t, JC–N ¼ 3.9 Hz), 57.1, 57.2, 61.9,
65.5, 116.2, 120.2, 121.4 (q, JC–F ¼ 321 Hz), 123.3, 124.7,
126.1, 126.3, 127.8, 128.4, 129.1, 129.5, 129.8, 133.1, 143.4,
147.4, 148.6, 151.2, 151.3, 167.0ppm; MS (APCI): m=z ¼
486.6 (Cþ).
{3-[4-(Chlorophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta-
[c]quinoline-8-carbonyloxy]propyl}trimethylammonium
bistrifluoromethanesulfonamide (7ca, C29H34ClF6N3O6S2)
Following procedure A using 4-chlorobenzaldehyde 5c and
cyclopentadiene 6a provided expected product 7ca as a solid
1
in 89% yield; mp 202–204ꢁC; H NMR (300 MHz, acetone-
d6): ꢁ ¼ 1.60–1.80 (m, 1H), 2.35–2.58 (m, 3H), 3.01–3.20 (m,
1H), 3.40 (s, 9H), 3.70–3.90 (m, 2H), 4.10–4.22 (m, 1H),
4.42 (t, 2H, J ¼ 5.8 Hz), 4.90–5.00 (m, 1H), 5.58–5.65 (m,
1H), 5.70–5.80 (m, 1H), 5.93–6.05 (m, 1H), 6.85 (d, 1H,
J ¼ 8.4 Hz), 7.30–7.70 (m, 6H) ppm; 13C NMR (50 MHz,
acetone-d6): ꢁ ¼ 24.2, 32.6, 46.7, 47.0, 54.2 (t, JC–N ¼ 4.0 Hz),
57.5, 61.9, 65.5, 116.5 120.4, 121.4 (q, JC–F ¼ 321 Hz), 125.9,
129.4, 129.5, 129.6, 131.1, 132.3, 133.6, 135.6, 142.6, 152.2,
167.1ppm; MS (APCI): m=z ¼ 425.3 (Cþ).
{3-[6-(4-Bromophenyl)-5,6a,7,11b-tetrahydro-6H-indeno-
[2,1-c]quinoline-2-carbonyloxy]propyl}trimethylammonium
bistrifluoromethanesulfonamide (7db, C33H36BrF6N3O6S2)
Following procedure A using 4-bromobenzaldehyde 5d and
indene 6b provided expected product 7db as a yellow solid in
1
{3-[4-(Bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta-
[c]quinoline-8-carbonyloxy]propyl}-trimethylammonium
bistrifluoromethanesulfonamide (7da, C29H34BrF6N3O6S2)
Following procedure A using 4-bromobenzaldehyde 5d and
cyclopentadiene 6a provided expected product 7da as a solid
83% yield. H NMR (300 MHz, acetone-d6): ꢁ ¼ 2.15–2.36
(m, 2H), 2.98–3.05 (m, 2H), 3.37 (s, 9H), 3.38–3.44 (m,
2H), 4.17 (t, 2H, J ¼ 5.6 Hz), 4.34 (m, 1H), 4.73 (bl, 1H),
6.24 (d, 1H, J ¼ 8.3 Hz), 6.94 (m, 1H), 7.01–7.21 (m, 3H),
7.27 (s, 1H), 7.46–7.74 (m, 2H), 8.05 (d, 2H, J ¼ 8.3 Hz) ppm;
13C NMR (75 MHz, acetone-d6): ꢁ ¼ 22.1, 38.2, 45.1, 45.7,
1
in 90% yield; mp 122–124ꢁC; H NMR (300 MHz, acetone-
53.1 (t, JC–N ¼ 4 Hz), 54.9, 61.7, 63.8, 114.0, 121.4 (q, JC–F
¼
d6): ꢁ ¼ 1.60–1.80 (m, 1H), 2.35–2.58 (m, 3H), 3.01–3.20 (m,
321 Hz), 121.5, 123.8, 125.2, 125.8, 126.5, 127.3, 127.4, 127.6,
1H), 3.40 (s, 9H), 3.70–3.90 (m, 2H), 4.10–4.22 (m, 1H),

Task Specific Onium Salts
1173
129.0, 129.9, 137.3, 142.0, 145.9, 146.3, 150.1, 165.9ppm;
MS (APCI): m=z ¼ 519.1 (Cþ).
yield; mp 186–188ꢁC; 1H NMR (300MHz, acetone-d6):
ꢁ ¼ 1.58–1.80 (m, 1H), 2,40–2,64 (m, 3H), 3.14–3.28 (m,
1H), 3.42 (s, 9H), 3.73–3.92 (m, 2H), 4.15–4.30 (m, 1H),
4.48 (t, 2H, J ¼ 6.0 Hz), 4.65–4.78 (m, 1H), 5.48–5.60 (m,
1H), 5.63–5.78 (m, 1H), 5.85–6.00 (m, 1H), 7.03–7.25 (m,
2H), 7.58–7.76 (m, 3H), 7.98–8.12 (m, 2H) ppm; 13C NMR
(50 MHz, acetone-d6): ꢁ ¼ 23.6, 32.3, 44.2, 46.2, 46.5, 47.0,
53.7, 57.2, 57.6, 62.4, 64.9, 64.9, 111.0, 113.5, 115.0, 119.5,
121.4, 127.7, 129.8, 130.5, 131.9, 132.8, 148.8, 166.5 ppm;
MS (APCI): m=z ¼ 436.1 (Cþ).
{3-[2-(4-Nitrophenyl)-4-phenyl-1,2,3,4-tetrahydroquinoline-
6-carbonyloxy]propyl}trimethylammonium bistrifluoro-
methanesulfonamide (7bc, C32H36F6N4O8S2)
Following procedure A using 4-nitrobenzaldehyde 5b and
styrene 6c provided expected product 7bc as a yellow solid
1
in 79% yield; mp 128–130ꢁC; H NMR (300 MHz, acetone-
d6): ꢁ ¼ 2.10–2.28 (m, 1H), 2.30–2.43 (m, 3H), 3.38 (s, 9H),
3.42–3.48 (m, 1H), 3.62–3.75 (m, 2H), 4.28 (t, 2H, J ¼
5.7 Hz), 4.32–4.42 (m, 1H), 4.90–5.01 (m, 1H), 6.80 (d, 1H,
J ¼ 8.7 Hz), 7.23–7.44 (m, 6H), 7.60–7.70 (m, 1H), 7.82 (d,
2H, J ¼ 8.7 Hz), 8.25 (d, 2H, J ¼ 9.1 Hz) ppm; 13C NMR
{3-[4-(8-Bromo-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]-
quinolin-4-yl)benzoyloxy]propyl}trimethylammonium
tetrafluoroborate (9ca, C27H30BrF6N3O6S2)
Following procedure B using 4-bromoaniline 8c and cyclo-
pentadiene 6a provided expected product 9ca as a brownish
solid in 88% yield; mp 190–192ꢁC; 1H NMR (300 MHz,
acetone-d6): ꢁ ¼ 1.54–1.80 (m, 1H), 2.40–2.60 (m, 2H),
2.88–3.20 (m, 2H), 3.40 (s, 9H), 3.75–3.95 (m, 2H), 4.02–
4.20 (m, 1H), 4.55 (t, 2H, J ¼ 5.9 Hz), 4.72–4.80 (m, 1H),
5,58–5,75 (m, 1H), 5.7–5.8 (m, 1H), 5.93–6.05 (m, 1H),
6.70–6.81 (m, 1H), 7.01–7.30 (m, 2H), 7.65 (d, 2H, J ¼
8.2 Hz), 8.05 (d, 2H, J ¼ 8.3 Hz) ppm; 13C NMR (50 MHz,
acetone-d6): ꢁ ¼ 22.5, 31.2, 45.1, 45.8, 53.0 (t, JC–N ¼ 4.0 Hz),
57.0, 61.3, 63.9, 109.7, 117.8, 126.7, 128.3, 128.7, 128.8,
129.5, 130.2, 131.3, 133.9, 145.3, 148.4, 167.1ppm; MS
(APCI): m=z ¼ 470.1 (Cþ).
(50 MHz, acetone-d6): ꢁ ¼ 24.1, 42.0, 45.2, 54.2 (t, JC–N
¼
4.0 Hz), 57.2, 65.4 (t, JC–N ¼ 3.2Hz), 114.8, 118.7, 121.4
(q, JC–F ¼ 321 Hz), 124.9, 124.9, 125.2, 128.1, 129.1, 130.0,
130.0, 130.3, 130.5, 132.4, 145.7, 148.8, 151.3, 152.6,
167.0ppm; MS (APCI): m=z ¼ 474.3 (Cþ).
{3-[2-(4-Bromophenyl)-4-phenyl-1,2,3,4-tetrahydroquino-
line-6-carbonyloxy]propyl}trimethylammonium
bistrifluoromethanesulfonamide (7dc, C32H36BrF6N3O6S2)
Following procedure A using 4-bromobenzaldehyde 5d and
styrene 6c provided expected product 7dc as a solid in 86%
yield. 1H NMR (300MHz, acetone-d6): ꢁ ¼ 2.09–2.18 (m,
1H), 2.40–2.52 (m, 3H), 3.37 (s, 9H), 3.40–3.45 (m, 1H),
3.62–3.75 (m, 2H), 4.20 (t, 2H, J ¼ 5.7 Hz), 4.28–4.39 (m,
1H), 4.90–5.01 (bl, 1H), 6.85 (d, 1H, J ¼ 8.7 Hz), 7.18–7.23
(m, 9H), 7.60–7.65 (m, 1H), 7.82 (s, 1H) ppm; 13C NMR
(75 MHz, acetone-d6): ꢁ ¼ 24.1, 38.2, 42.0, 46.1, 54.2 (t,
JC–N ¼ 4.0 Hz), 59.9, 65.1 (t, JC–N ¼ 3.2 Hz), 114.8, 118.7,
121.4 (q, JC–F ¼ 321 Hz), 124.9, 125.1, 125.9, 128.1, 129.14,
129.8, 130.5, 130.7, 131.0, 132.4, 145.7, 148.8, 151.4, 152.6,
165.6ppm.
{3-[4-(2-Bromo-5,6a,7,11b-tetrahydro-6H-indeno[2,1-c]-
quinolin-6-yl)benzoyloxy]propyl}trimethylammonium
tetrafluoroborate (9cb, C31H32BrF6N3O6S2)
Following procedure B using 4-bromoaniline 8c and indene
6b provided expected product 9cb as a yellow solid in 92%
1
yield; mp 210–212ꢁC; H NMR (300 MHz, CD3CN): ꢁ ¼
2.15–2.35 (m, 1H), 2.40–2.58 (m, 3H), 3.15–3.22 (m, 2H),
3.40 (s, 9H), 3.75–4.05 (m, 2H), 4.43–4.68 (m, 3H), 4.80–
4.95 (m, 1H), 6.75 (d, 1H, J ¼ 8.6 Hz), 6.95–7.22 (m, 3H),
7.40–7.75 (m, 4H), 7.92–8.85 (m, 3H) ppm; 13C NMR
(75 MHz, CD3CN): ꢁ ¼ 22.1, 37.1, 45.0, 46.7, 53.2 (t,
JC–N ¼ 4 Hz), 55.6, 61.7; 62.7, 114.9, 121.6, 123.8, 125.2,
125.4, 126.5, 127.2, 127.4, 127.6, 129.0, 129.9, 137.3,
142.0, 145.9, 147.3, 152.6, 166.0 ppm; MS (APCI): m=z ¼
520.0 (Cþ).
{3-[4-(3a,4,5,9b-Tetrahydro-3H-cyclopenta[c]quinolin-4-
yl)benzoyloxy]propyl}trimethylammonium tetrafluoroborate
(9aa, C27H31F6N3O6S2)
Following procedure B using aniline 8a and cyclopentadiene
6a provided expected product 9aa as a solid in 77% yield; mp
1
186–188ꢁC; H NMR (300 MHz, acetone-d6): ꢁ ¼ 1.58–1.75
(m, 1H), 2.40–2.64 (m, 3H), 2.77–2.98 (br, 1H), 3.00–3.15
(m, 1H), 3.40 (s, 9H), 3.77–3.92 (m, 2H), 4.03–4.15 (m,
1H), 4.46 (t, 2H, J ¼ 5.9Hz), 4.68–4.76 (m, 1H), 5.55–5.62
(m, 1H), 5.81–5.92 (m, 1H), 6.58–7.13 (m, 4H), 7.60 (d, 2H,
J ¼ 8.3 Hz), 8.05 (d, 2H, J ¼ 8.4 Hz) ppm; 13C NMR (50 MHz,
acetone-d6): ꢁ ¼ 23.6, 32.2, 46.7, 47.1, 53.7 (t, JC–N ¼ 3.8 Hz),
58.2, 62.4, 64.8, 117.0, 119.5, 126.5, 126.9, 127.6, 129.5,
129.6, 130.2, 130.4, 135.4, 146.9, 149.8, 166.6 ppm; MS
(APCI): m=z ¼ 391.4 (Cþ).
Methyl 4-(8-bromo-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]-
quinolin-4-yl)benzoate CAS [347362-64-5]
(10aa, C20H19NO2)
To a solution of compound 9aa (1mmol) in methanol (2cm3)
was added commercial 7 N NH3 solution in methanol (10cm3).
After vigorous stirring at 25ꢁC for 18h, the solvent was elim-
inated under reduced pressure. After extraction from residue
using 3ꢂ30cm3 Et2O, combined organic fractions were con-
centrated under vacuum and subsequently purified by flash
chromatography on silica gel 60F 254 (Merck) using CH2Cl2
as eluent. Concentration under reduced pressure afforded 10aa
in 85% yield as a white powder. 1H NMR (200 MHz, CDCl3):
ꢁ ¼ 2.19–2.25 (m, 1H), 2.40–2.52 (m, 1H), 3.15–3.24 (m,
1H), 3.96 (s, 3H), 4.02–4.12 (m, 1H), 4.54 (bl, 1H), 4.62
{3-[4-(9-Nitro-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]-
quinolin-4-yl)benzoyloxy]propyl}trimethylammonium
tetrafluoroborate (9ba, C27H30F6N4O8S2)
Following procedure B using 3-nitroaniline 8b and cyclopen-
tadiene 6a provided expected product 9ba as a solid in 90%

1174
F. Hassine et al.: Task Specific Onium Salts
(m, 1H), 5.57–5.60 (m, 1H), 5.62–5.65 (m, 1H), 6.53–6.71
(m, 2H), 6.96–7.12 (m, 2H), 7.31 (d, 2H, J ¼ 8.7 Hz), 7.82 (d,
2H, J ¼ 8.7Hz) ppm; APCI-MS: m=z MS (APCI): m=z ¼
306.1.
[11] Vaultier M, Gmouh S, Hassine F (2005) FR2003-8413
2857360
[12] Vaultier M, Gmouh S (2004) FR2002-11910 2845084
[13] Wasserscheid P, Welton T (eds) (2003) Ionic Liquids in
Synthesis
[14] Baudequin C, Baudoux J, Levillain J, Cahard D,
Gaumont A-C, Plaquevent J-C (2003) Tetrahedron:
Asymmetr 14: 3081
References
[1] Nicolaou KC, Hanko R, Hartwig W (2002) Handbook of
Combinatorial Chemistry: Drugs, Catalysts, Materials,
vol 1. Wiley-VCH, Weinheim
[15] James H, Davis J (2004) Chem Lett 33: 1072
[16] Vaultier M, Roche C, Gmouh S, Commercon A (2006)
FR2005-1557 2882057
[2] Nicolaou KC, Hanko R, Hartwig W (2002) Handbook of
Combinatorial Chemistry: Drugs, Catalysts, Materials,
vol 2. Wiley-VCH, Weinheim
[3] Roller S, Siegers C, Haag R (2004) Tetrahedron 60:
8711
[4] Bergbreiter DE (2002) Chem Rev 102: 3345
[5] Gravert DJ, Janda KD (1997) Chem Rev 97: 489
[6] Toy PH, Janda KD (2000) Acc Chem Res 33: 546
[7] Hellermann H, Lucas H-W, Maul J, Pillai VNR, Mutter
M (1983) Makromol Chem 184: 2603
[17] Riisager A, Fehrmann R, Haumann M, Wasserscheid P
(2006) Eur J Inorg Chem: 695
[18] Jain N, Kumar A, Chauhan S, Chauhan SMS (2005)
Tetrahedron 61: 1015
[19] Song CE (2004) Chem Comm: 1033
[20] Demaude T, Knerr L, Pasau P (2004) J Comb Chem 6:
768
[21] Basso A, Banfi L, Riva R, Piaggio P, Guanti G (2003)
Tetrahedron Lett 44: 2367
[22] Dondoni A, Massi A, Minghini E, Bertolasi V (2004)
Tetrahedron 60: 2311
[23] Grieco PA, Bahsas A (1988) Tetrahedron Lett 29: 5855
[24] Kobayashi S, Ishitani H, Nagayama S (1995) Synthesis:
1195
[8] Douglas SP, Whttfield DM, Krepinsky JJ (1991) J Am
Chem Soc 113: 5095
[9] Koester H (1972) Tetrahedron Lett: 1535
[10] Welton T (1999) Chem Rev 99: 2071