Synthesis and characterization of new chiral azolinium salts, precursors to N-heterocyclic carbenes, derived from l-proline

Article abstract of DOI:10.1055/s-0033-1340215

A short and flexible procedure for the preparation of seven chiral azolinium and five functionalized chiral azolinium salts, precursors to N-heterocyclic carbenes, derived from l-proline has been developed. Moderate to good overall yields were obtained. Some NHC dimers and thiones were isolated. X-ray crystal structure determinations of two [Rh-NHC] complexes were also reported.

Full text of DOI:10.1055/s-0033-1340215

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PAPER
paper
Synthesis and Characterization of New Chiral Azolinium Salts, Precursors to
N-Heterocyclic Carbenes, Derived from L-Proline
Synthesis and Characterization of New Chiral Azolinium Salts
Amélia Thomasset,a Lucie Bouchardy,a Chloée Bournaud,a Régis Guillot,b Martial Toffano,a Giang Vo-Thanh*a
a
Laboratoire de Catalyse Moléculaire, Institut de Chimie Moléculaire et des Matériaux d’Orsay (ICMMO), UMR CNRS 8182,
Université Paris-Sud, 91405 Orsay Cedex, France
E-mail: giang.vo-thanh@u-psud.fr
b
CNRS, Délégation Ile de France Sud, Orsay, France
Received: 29.08.2013; Accepted after revision: 16.10.2013
As reported, azolium and azolinium salts are often used as
Abstract: A short and flexible procedure for the preparation of sev-
precursors to metal–NHC complexes,1–4 but they have
en chiral azolinium and five functionalized chiral azolinium salts,
also found applications on their own as organocatalysts6
precursors to N-heterocyclic carbenes, derived from L-proline has
been developed. Moderate to good overall yields were obtained.
and ionic liquids.7 These research areas are currently un-
Some NHC dimers and thiones were isolated. X-ray crystal struc- der investigation because of their importance for develop-
ture determinations of two [Rh-NHC] complexes were also report-
ed.
ing ‘greening’ chemical processes.
A useful method for the preparation of azolinium salts
Key words: azolinium salts, N-heterocyclic carbene, L-proline, mi-
containing a saturated backbone is the condensation of an
crowave activation
N,N′-disubstituted alkanediamine and an inorganic am-
monium salt with a trialkyl orthoester used as both a re-
agent and the solvent, in the presence of a catalytic
N-Heterocyclic carbenes (NHCs) have attracted great at-
amount of acid.8 Several modifications of the experimen-
tention as they have been proven to act as efficient ligands
tal reaction conditions for this method have been reported
in coordination chemistry and homogeneous catalysis.1 In
in literature.9 In all cases, long reaction times (from a few
many cases, NHC complexes show higher thermal stabil-
hours to several days) together with prolonged reflux
ity and catalytic activity than their phosphine counterparts
heating conditions are required to obtain good conver-
partially owing to the strong metal–NHC bonds and the
sions. In 2008, Delaude et al. described a facile micro-
wave-assisted synthesis of cyclic amidinium salts. The
transformation is highly compatible with a wide range of
high σ-donating ability of NHC ligands.2 The incorpora-
tion of the carbene functionality into ligand systems offers
great opportunities for ligand design and the discovery of
substituents and counterions.10
new efficient catalysts.3 Chiral N-heterocyclic carbenes
For our synthesis, we chose (S)-N-(benzyloxycarbon-
yl)proline (2), which is commercially available, as the
starting material.
are well established as efficient alternatives to chiral phos-
phine ligands in asymmetric synthesis processes.4
As part of our own program of studies, we have recently
described the rhodium-catalyzed asymmetric transfer hy-
drogenation of aromatic ketones using chiral NHC ligands
derived from (S)-pyroglutamic acid. Good yields and en-
antioselectivities (up to 94% yield and 90% ee) were ob-
served (Scheme 1).5 Here, we report the synthesis and
characterization of novel functionalized chiral azolinium
salts, precursors to NHCs, derived from L-proline, a natu-
rally available product.
The synthetic route for the chiral azolinium salts 6 is sum-
marized in Scheme 2.
Our synthesis was initiated by transforming (S)-N-(ben-
zyloxycarbonyl)proline (2) into the corresponding amides
3 by treatment with ethyl chloroformate in the presence of
N-methylmorpholine and a variety of amines. The cleav-
age of the N-Cbz protective group in 3 by hydrogenolysis
under a hydrogen atmosphere at ordinary pressure in the
presence of 5% palladium on carbon catalyst followed by
the reduction of the amide function using lithium alumi-
num hydride afforded the disubstituted alkanediamines 5
in moderate to good yields. Subsequently, the diamines 5
were converted into the azolinium salts 6 by heating with
a large excess of triethyl orthoformate along with an
equivalent of potassium hexafluorophosphate at 80 °C for
12 hours according to the protocol reported in literature.11
However, after many repeated experiments, the desired
product was not detected. Only the diamide 7 was isolated
and its structure was determined by NMR and MS analy-
sis methods (Scheme 3).
O
OH
[Rh(cod)Cl]2 (1 mol%)
N
N
Me
*
Ar
Ar
1 (6 mol%), t-BuOK
i-PrOH, KOH (5 mol%)
80 °C, 20 h
yield up to 90%
ee up to 90%
OTs
N
H
1
O
Scheme 1 Asymmetric transfer hydrogenation of aromatic ketones
SYNTHESIS 2014, 46, 0242–0250
Advanced online publication: 14.11.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1340215; Art ID: SS-2013-Z0586-OP
© Georg Thieme Verlag Stuttgart · New York

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Synthesis and Characterization of New Chiral Azolinium Salts
243
b
a
OH
NHR
NHR
N
N
N
H
O
O
O
4
Cbz
Cbz
3
2
4a, R = phenyl (quant.)
4b, R = benzyl (quant.)
3a, R = phenyl (95%)
3b, R = benzyl (93%)
4c, R = 2,6-diisopropylphenyl (quant.)
4d, R = (S)-1-phenylethyl (89%)
4e, R = (R)-1-phenylethyl (quant.)
4f, R = 1-naphthyl (92%)
3c, R = 2,6-diisopropylphenyl (quant.)
3d, R = (S)-1-phenylethyl (quant.)
3e, R = (R)-1-phenylethyl (98%)
3f, R = 1-naphthyl (98%)
4g, R = 2-methoxyphenyl (98%)
3g, R = 2-methoxyphenyl (98%)
c
d
NHR
N
H
N
N
5
PF6
R
5a, R = phenyl (52%)
5b, R = benzyl (63%)
6
5c, R = 2,6-diisopropylphenyl (82%)
5d, R = (S)-1-phenylethyl (86%)
5e, R = (R)-1-phenylethyl (79%)
5f, R = 1-naphthyl (91%)
6a, R = phenyl (49%)
6b, R = benzyl (53%)
6c, R = 2,6-diisopropylphenyl (58%)
6d, R = (S)-1-phenylethyl (93%)
6e, R = (R)-1-phenylethyl (92%)
6f, R = 1-naphthyl (92%)
6g, R = 2-methoxyphenyl (22%)
5g, R = 2-methoxyphenyl (22%)
Scheme 2 Synthesis of chiral azolinium salts 6. Reagents and conditions: (a) NMM, ClCO2Et, RNH2, EtOAc, 0 °C to r.t., 15 h; (b) Pd/C, H2,
MeOH, r.t., 15 h; (c) LiAlH4, THF reflux, 15 h; (d) HC(OEt)3, NH4PF6, MW, 145 °C, 5 min.
asymmetric catalysis. Thus, functionalized chiral azolini-
1. MeOH–HCl
O
H
Et2O, 5 min
um salts 11 were synthesized from diamines 10, which
were easily obtained in good overall yields (41–90%) in
three steps from N-Cbz-protected L-proline 2 (Scheme 4).
Ph
HC(OEt)3
toluene, 80 °C, 12 h
N
NH
Ph
N
N
H
2. KPF6, H2O
5
O
H
7
R
H
OH
∗
H2N
Scheme 3 Formation of diamide 7
N
b
OH
∗
OH
N
N
a
O
R
O
Cbz
Cbz
We turned our attention to the use of microwave irradia-
tion. This technique was widely developed in our labora-
tory and in other research groups.12 The combination of
solvent-free synthesis conditions and microwave irradia-
tion considerably reduces the reaction time, enhances con-
versions as well as selectivity, and sometimes enables the
preparation of molecules that are impossible to synthesize
using classical heating conditions.13
8
2
8a, R = H (87%)
8b, R = (S)-i-Pr (94%)
8c, R = (S)-t-Bu (95%)
8d, R = (R)-Ph (89%)
8e, R = (S)-Bn (75%)
H
N
H
N
∗
∗
c
OH
OH
N
H
N
O
R
R
•HCl
H
9
10
10a, R = H (48%)
10b, R = (S)-i-Pr (96%)
10c, R = (S)-t-Bu (91%)
10d, R = (R)-Ph (91%)
10e, R = (S)-Bn (72%)
The cyclization was thus carried out in a ‘one-pot’ reac-
tion using amines 5, triethyl orthoformate, and ammoni-
um hexafluorophosphate under microwave irradiation
conditions at 145 °C for five minutes. Generally speaking,
azolinium salts 6 were isolated in moderate to good yields
(Scheme 2). Under identical reaction conditions (same
temperature, same reaction time, etc.) using a thermostatic
oil bath (conventional heating), only traces of the desired
products were detected. Using this experimental protocol,
seven new chiral azolinium salts were synthesized in four
steps from (S)-N-(benzyloxycarbonyl)proline (2) in 5–
75% overall yields.
9a, R = H (quant.)
9b, R = (S)-i-Pr (quant.)
9c, R = (S)-t-Bu (96%)
9d, R = (R)-Ph (50%)
9e, R = (S)-Bn (quant.)
Scheme 4 Synthesis of chiral diamines 10. Reagents and conditions:
(a) NMM, ClCO2Et, EtOAc, –15 °C to r.t., 15 h; (b) Pd/C, H2, MeOH,
r.t., 15 h; (c) 1. BH3·THF reflux, 15 h, 2. HCl, dioxane, CH2Cl2, r.t.,
30 min.
Using the same strategy previously described in Scheme
2, functionalized chiral azolinium salts 11a–d were isolat-
ed in moderate yields after purification by flash chroma-
tography on silica gel. On the other hand, owing to the
degradation under microwave irradiation, the chiral azo-
linium salt 11e was synthesized by treatment of the di-
amine 10 with a large excess of trimethyl orthoformate
followed by anion exchange with potassium hexafluoro-
We then proceeded to synthesize the functionalized chiral
azolinium salts 11 possessing not only a hydroxyl func-
tion, but also a supplementary stereogenic center on the
alkyl chain in order to study their effects on prospective
applications of these chiral salts as precursors to NHCs in
© Georg Thieme Verlag Stuttgart · New York
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244
A. Thomasset et al.
PAPER
1) CH(OMe)3
toluene, 100 °C, 15 h
N
PF6
N
2) KPF6
H2O, r.t., 20 min
OH
H
N
H
HCl, dioxane
*
N
OH
OH
N
H
N
H
CH2Cl2, r.t., 30 min
•HCl
11e
R
R
R = (S)-Bn (18%)
10
NH4PF6
CH(OMe)3
MW, 100 °C
5 min
MW, 100 °C
5 min
CH(OMe)3
N
N
N
Cl
N
N
Cl
PF6
Cl
N
N
N
OH
OH
R = H (30%)
OH
OH
Ph
11a
11d
R = (R)-Ph (34%)
11b
R = (S)-i-Pr (46%)
11c
R = (S)-t-Bu (44%)
Scheme 5 Synthesis of functionalized chiral azolinium salts 11
phosphate. Scheme 5 summarizes the synthesis of these for C=S appear at δ = 186.2, 187.6, and 185.4 for 13b,
functionalized chiral azolinium salts 11.
13c, and 13e, respectively (Scheme 7).
Next, we were interested in characterizing our NHCs.
Some azolinium salts were selected for this study. Treat-
ment of the chiral azolinium salts 6a–c and 6e with potas-
sium tert-butoxide in tetrahydrofuran at room temperature
led to the formation of the corresponding NHC dimers 12,
and not free NHCs, in good yields. These NHC dimers are
quite stable on storage in a glovebox and their structures
were confirmed by NMR analysis (Scheme 6).
R
N
N
N
N
N
N
C6D6, r.t., 2 h
R
S
R
13
13b, R = benzyl (59%)
13c, R = 2,6-diisopropylphenyl (95%)
13e, R = (R)-1-phenylethyl (48%)
12
Scheme 7 Formation of thiones 13
N
1) t-BuOK, r.t.
Finally, the ability of the NHC dimers to form transition-
metal complexes was also evaluated. The reaction of 12b,
12c, and 12e with [Rh(cod)Cl]2 in tetrahydrofuran at room
temperature for 24 hours led to the formation of the ex-
pected [Rh-NHC] complexes 14b, 14c, and 14e, which
were isolated, after purification by flash chromatography
on silica gel, in 18–55% yields as air-stable yellow solids
(Scheme 8). NMR and ESI analyses and especially the X-
ray diffraction for 14b (Figure 1) and 14e (Figure 2) con-
firmed the formation of these [Rh-NHC] complexes.
45 min
R
N
N
N
R
PF6
2) hexane
N
N
R
6
12
12a, R = phenyl (84%)
12b, R = benzyl (77%)
12c, R = 2,6-diisopropylphenyl (95%)
12e, R = (R)-1-phenylethyl (93%)
Scheme 6 Formation of NHC dimers 12
To characterize the unstable free NHCs, a useful method
is to transform directly a free NHC to its derivative by re-
action with sulfur or selenium.14 These adducts are very
stable and could be characterized by different analysis
methods. Thus, treatment of NHC dimers 12b, 12c, and
12e with sulfur (S8) in the presence of benzene-d6 at room
temperature for two hours led to the formation of thiones
13 in moderate to good yields. Their structures were con-
firmed by NMR and ESI analyses. The 13C NMR signals
R
R
N
N
N
N
[Rh(cod)Cl]2
N
Rh
N
Cl
14
R
12
14b, R = benzyl (55%)
14c, R = 2,6-diisopropylphenyl (18%)
14e, R = (R)-1-phenylethyl (37%)
Scheme 8 Formation of [Rh-NHC] complexes 14
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Synthesis and Characterization of New Chiral Azolinium Salts
245
NHC] complexes were confirmed by different analysis
methods in particular X-ray diffraction analysis. The effi-
ciency of these NHC ligands has been evaluated in asym-
metric allylic substitution and in conjugate addition of
Grignard reagent to α,β-unsaturated ketones. The results
of these studies will be communicated in due course.
Microwave experiments were conducted using a CEM Discover
Synthesis Unit (monomode system) operating at 2450 MHz moni-
tored by a PC computer.17 Melting points were measured on a
Kofler block. The NMR spectra were recorded in CDCl3, CD2Cl2,
C6D6, DMSO-d6, or CD3OD. 1H NMR spectra were recorded at 400,
360, 300, or 250 MHz relative to TMS as internal standard. 13C
NMR spectra were recorded at 100, 90, 75 MHz. IR spectra were re-
corded on a FT-IR Perkin-Elmer instrument. Mass spectra were re-
corded on a MAT 95S Finnigan-Thermo mass spectrometer. TLC
experiments were carried out in 0.25-mm thick silica gel plates
Merck Kiesegel F254 and visualization was accomplished by UV
light or phosphomolybdic acid solution. The columns were hand-
packed with silica gel 60 (200–300 mesh). X-ray diffraction data
was collected by using a Kappa X8 APPEX II Bruker diffractome-
ter with graphite-monochromated MoKα radiation (λ = 0.71073 Å).
Figure 1 ORTEP drawing representation of the molecular structure
of 14b. Ellipsoids are drawn at the 30% probability level. Selected
bond distances and angles: Rh–Cl = 2.3754(7) Å; Rh–C(10) =
1.994(2) Å; Rh–C(14) = 2.229(3) Å; Rh–C(21) = 2.191(3) Å; Rh–
C(17) = 2.095(3) Å; Rh–C(18) = 2.131(3) Å; C(10)–N(1) = 1.338(3)
Å; C(10)–N(2) = 1.354(3) Å; N(1)–C(10)–N(2) = 108.6(2)°.
All reactions were carried out in Schlenk tubes under an argon at-
mosphere. All solvents were distilled from appropriate drying
agents prior to use. All reagents are commercially available and
were used without further purification.
Synthesis of Chiral Azolinium Salts 6
The synthesis of compounds 3, 4, and 5 was carried out according
to the protocol described in literature. Spectral data of these com-
pounds were in accordance with reported values.15
Synthesis of Chiral Azolinium Salts 6 by Cyclization of Disub-
stituted Alkanediamines 5 under Microwave Activation; Gen-
eral Procedure
A mixture of diamine 5 (5 mmol), NH4PF6 (1.05 equiv) and triethyl
orthoformate (5 equiv) was subjected to microwave irradiation at
145 °C for 5 min. The mixture was brought to r.t. and Et2O (15 mL)
was added. The product was precipitated, filtered, and washed with
Et2O to afford the azolinium salts 6 as solids.
(S)-2-Phenyl-5,6,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazol-2-
ium Hexafluorophosphate (6a)
Yellow solid; yield: 813 mg (2.45 mmol, 49%); mp 195 °C.
[α]D25 –248.4 (c 0.95, CH2Cl2).
IR (neat): 2955, 2924, 2854, 1627, 1597, 1515, 1463, 1263 cm–1.
1H NMR (360 MHz, DMSO-d6): δ = 1.62–1.83 (m, 1 H), 1.94–2.28
(m, 3 H), 3.59 (ddd, J = 4.0, 9.0, 11.1 Hz, 1 H), 3.73–3.91 (m, 1 H),
4.24–4.67 (m, 3 H), 7.24–7.59 (m, 5 H), 9.29 (s, 1 H).
13C NMR (75 MHz, DMSO-d6): δ = 24.5, 29.6, 45.3, 52.6, 63.3,
117.9, 123.8, 126.5, 136.4, 155.6.
HRMS (ESI): m/z [M]+ calcd for C12H15N2: 187.1230; found:
187.1226.
Figure 2 ORTEP drawing representation of the molecular structure
of 14e. Ellipsoids are drawn at the 30% probability level. Selected
bond distances and angles: Rh–Cl = 2.3761(3) Å; Rh–C(10) =
2.0021(13) Å; Rh–C(14) = 2.2342(13) Å; Rh–C(21) = 2.2055(12) Å;
Rh–C(17) = 2.1032(13) Å; Rh–C(18) = 2.1202(13) Å; C(10)–N(1) =
1.3385(17) Å; C(10)–N(2) = 1.3564(17) Å; N(1)–C(10)–N(2) =
108.57(11)°.
(S)-2-Benzyl-5,6,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazol-2-
ium Hexafluorophosphate (6b)
Yellow solid; yield: 917 mg (2.65 mmol, 53%); mp 80 °C.
[α]D25 –222.7 (c 1.10, CH2Cl2).
IR (neat): 3096, 2965, 1633, 1497, 1369, 1207, 1083 cm–1.
In summary, we have developed a short and flexible pro-
cedure for the synthesis of seven chiral azolinium salts,
and five functionalized chiral azolinium salts, precursors
to N-heterocyclic carbene, derived from L-proline. Mod-
erate to good overall yields were obtained in all cases. The
structures of some NHC dimers, thiones, and two [Rh-
1H NMR (360 MHz, DMSO-d6): δ = 1.34–1.63 (m, 1 H), 1.77–2.16
(m, 3 H), 3.38 (td, J = 4.3, 9.9 Hz, 1 H), 3.61 (dd, J = 6.1, 12 Hz, 1
H), 3.69–3.87 (m, 2 H), 4.19–4.38 (m, 1 H), 4.70 (d, J = 6 Hz, 2 H),
7.30–7.53 (m, 5 H), 8.59 (s, 1 H).
13C NMR (75 MHz, DMSO-d6): δ = 24.0, 29.6, 45.1, 51.1, 52.0,
63.2, 128.4, 128.5, 128.9, 142.9, 159.6.
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246
A. Thomasset et al.
PAPER
IR (neat): 3148, 2959, 1614, 1591, 1253, 1128, 1023 cm–1.
HRMS (ESI): m/z [M]+ calcd for C13H17N2: 201.1386; found:
201.1382.
1H NMR (360 MHz, DMSO-d6): δ = 1.64–1.84 (m, 1 H), 1.95–2.29
(m, 3 H), 3.48–3.66 (m, 1 H), 3.82–3.89 (m, 1 H), 3.91 (s, 3 H),
4.26–4.62 (m, 3 H), 7.01–7.49 (m, 4 H), 9.05 (s, 1 H).
13C NMR (90 MHz, DMSO-d6): δ = 24.4, 29.6, 45.3, 54.8, 56.2,
62.6, 112.8, 121.0, 122.9, 128.8, 151.6, 158.2.
(S)-2-(2,6-Diisopropylphenyl)-5,6,7,7a-tetrahydro-1H-pyrro-
lo[1,2-c]imidazol-2-ium Hexafluorophosphate (6c)
Yellow solid; yield: 1.21 g (2.9 mmol, 58%); mp 189 °C.
[α]D25 –174.4 (c 0.90, CH2Cl2).
HRMS: m/z [M]+ calcd for C16H17N2: 217.1335; found: 217.1338.
IR (neat): 3119, 2969, 2875, 1622, 1475, 1461, 1334, 1269, 1097
cm–1.
1H NMR (250 MHz, CDCl3): δ = 1.04–1.44 (m, 12 H), 1.67–1.93
(m, 1 H), 2.07–2.56 (m, 3 H), 2.68–3.01 (m, 2 H), 3.66 (ddd, J = 4.3,
10.3, 12.1 Hz, 1 H), 3.92–4.29 (m, 3 H), 4.58–4.83 (m, 1 H), 7.14–
7.34 (m, 2 H), 7.38–7.58 (m, 1 H), 7.95 (s, 1 H).
Synthesis of Functionalized Chiral Azolinium Salts 11
The synthesis of compounds 8 and 9 was carried out according to
the protocol described in the literature. Spectral data of these com-
pounds were in accordance with reported values.16
Synthesis of Diamine Hydrochloride 10; General Procedure
To a solution of amide 9 (3.3 mmol) in distilled THF (10 mL) was
added a 1 M solution of BH3·THF (13.2 mmol, 4 equiv). The result-
ing mixture was stirred overnight at reflux. After cooling to r.t., the
reaction was quenched with MeOH, and the solvent was evaporated
under reduced pressure. The residue was dissolved again in MeOH
(15 mL) and heated at reflux for 2 h. After removing solvent under
reduced pressure, the crude diamine was dissolved in CH2Cl2, and
4 M HCl in dioxane (6 equiv) was added at 0 °C. The mixture was
stirred for 30 min at r.t. The solvent was removed, and the residue
was dissolved in CH2Cl2, and Et2O was added to precipitate the
product. After filtration, the obtained powder was washed with
EtOAc to give the pure diamine hydrochloride 10.
13C NMR (90 MHz, CDCl3): δ = 24.1, 24.6, 28.6, 30.7, 45.5, 57.7,
64.3, 124.9, 129.5, 131.3, 146.0, 146.8, 158.2.
HRMS (ESI): m/z [M]+ calcd for C18H27N2: 271.2169; found:
271.2164.
(S)-2-[(S)-1-Phenylethyl]-5,6,7,7a-tetrahydro-1H-pyrrolo[1,2-
c]imidazol-2-ium Hexafluorophosphate (6d)
Yellow solid; yield: 1.67 g (4.65 mmol, 93%); mp 107 °C.
[α]D25 –191.2 (c 1.07, CH2Cl2).
IR (neat): 3124, 2984, 1633, 1497, 1457, 1347, 1270, 1106 cm–1.
1H NMR (360 MHz, CDCl3): δ = 1.41–1.58 (m, 1 H), 1.60 (d, J =
7.0 Hz, 3 H), 1.87–2.10 (m, 3 H), 3.37–3.46 (m, 1 H), 3.62 (dd, J =
6.1, 11.9 Hz, 1 H), 3.65–3.86 (m, 2 H), 4.19–4.32 (m, 1 H), 4.87 (q,
J = 6.9 Hz, 1 H), 7.32–7.48 (m, 5 H), 8.66 (s, 1 H).
13C NMR (90 MHz, DMSO-d6): δ = 19.8, 24.4, 30.0, 45.7, 51.3,
57.7, 63.2, 127.2, 129.0, 129.5, 138.8, 159.0.
(S)-2-(Pyrrolidin-2-ylmethylamino)ethanol Hydrochloride
(10a)
White solid; yield: 284 mg (1.58 mmol, 48%).
[α]D20 +16.47 (c 1.02, MeOH).
IR (neat): 3292, 2949, 2735, 2463, 1327, 1076 cm–1.
HRMS: m/z [M]+ calcd for C14H19N2: 215.1543; found: 215.1546.
1H NMR (360 MHz, CD3OD): δ = 1.83–2.00 (m, 1 H), 2.02–2.29
(m, 2 H), 2.31–2.51 (m, 1 H), 3.26–3.34 (m, 2 H), 3.40–3.56 (m, 2
H), 3.59–3.70 (m, 2 H), 3.86–3.97 (m, 2 H), 4.01–4.16 (m, 1 H).
13C NMR (90 MHz, CD3OD): δ = 24.2, 29.9, 47.0, 51.5, 57.7, 57.8,
68.1.
HRMS (ESI): m/z [M + H]+ calcd for C7H17N2O: 145.1341; found:
145.1335.
(S)-2-[(R)-1-Phenylethyl]-5,6,7,7a-tetrahydro-1H-pyrrolo[1,2-
c]imidazol-2-ium Hexafluorophosphate (6e)
Yellow solid; yield: 1.66 g (4.60 mmol, 92%); mp 82 °C.
[α]D25 –163.4 (c 1.1.5, CH2Cl2).
IR (neat): 3121, 2998, 1635, 1495, 1455, 1380, 1286, 1090 cm–1.
1H NMR (360 MHz, DMSO-d6): δ = 1.35–1.51 (m, 1 H), 1.63 (d,
J = 6.9 Hz, 3 H), 1.81–2.12 (m, 3 H), 3.36–3.47 (m, 1 H), 3.53 (dd,
J = 5.6, 12.1 Hz, 1 H), 3.69–3.88 (m, 2 H), 4.16–4.36 (m, 1 H), 4.93
(q, J = 6.9 Hz, 1 H), 7.31–7.52 (m, 5 H), 8.64 (s, 1 H).
13C NMR (90 MHz, DMSO-d6): δ = 19.9, 24.4, 30.0, 45.7, 52.0,
57.8, 63.2, 127.1, 129.0, 129.5, 139.0, 158.7.
HRMS: m/z [M]+ calcd for C14H19N2: 215.1543; found: 215.1539.
(S)-3-Methyl-2-[(S)-pyrrolidin-2-ylmethylamino]butan-1-ol
Hydrochloride (10b)
White solid; yield: 704 mg (3.17 mmol, 96%).
[α]D20 +9.39 (c 0.98, MeOH).
IR (neat): 3314, 2957, 2739, 2489, 1394, 1038 cm–1.
1H NMR (250 MHz, CD3OD): δ = 1.00–1.30 (m, 6 H), 1.80–2.01
(m, 1 H), 2.00–2.28 (m, 3 H), 2.30–2.48 (m, 1 H), 3.18–3.29 (m, 1
H), 3.38–3.53 (m, 2 H), 3.54–3.67 (m, 2 H), 3.79–3.99 (m, 2 H),
4.00–4.20 (m, 1 H).
13C NMR (75 MHz, CD3OD): δ = 18.0, 19.9, 24.1, 29.4, 30.0, 46.8,
48.1, 58.1, 67.4.
(S)-2-(Naphthalen-1-yl)-5,6,7,7a-tetrahydro-1H-pyrrolo[1,2-
c]imidazol-2-ium Hexafluorophosphate (6f)
Brown solid; yield: 1.76 g (4.60 mmol, 92%); mp 143 °C.
[α]D25 –165.6 (c 1.25, CH2Cl2).
IR (neat): 3113, 2983, 1629, 1396, 1338, 1266, 1093 cm–1.
1H NMR (360 MHz, DMSO-d6): δ = 0.98–1.8 (m, 1 H), 1.87–2.02
(m, 1 H), 2.04–2.18 (m, 1 H), 2.20–2.35 (m, 1 H), 3.62 (td, J = 3.9,
10.0 Hz, 1 H), 3.89–4.05 (m, 1 H), 4.37 (dd, J = 7.2, 11.2 Hz, 1 H),
4.50–4.62 (m, 1 H), 4.63–4.81 (m, 1 H), 7.54–7.86 (m, 4 H), 7.98–
8.23 (m, 3 H), 8.95 (s, 1 H).
13C NMR (90 MHz, DMSO-d6): δ = 25.0, 30.0, 45.5, 57.6, 64.4,
122.5, 130.3, 133.0, 134.4, 151.7, 160.0.
HRMS (ESI): m/z [M + H]+ calcd for C10H23N2O: 187.1810; found:
187.1805.
(S)-3,3-Dimethyl-2-[(S)-pyrrolidin-2-ylmethylamino]butan-1-
ol Hydrochloride (10c)
White solid; yield: 708 mg (3.00 mmol, 91%).
[α]D20 +9.39 (c 0.98, MeOH).
IR (neat): 3314, 2957, 2743, 1373, 1051 cm–1.
HRMS: m/z [M]+ calcd for C16H17N2: 237.1386; found: 237.1381.
1H NMR (250 MHz, CD3OD): δ = 1.15 (s, 9 H), 1.76–1.97 (m, 1 H),
2.00–2.21 (m, 2 H), 2.29–2.50 (m, 1 H), 3.22 (dd, J = 7.8, 4.0 Hz, 1
H), 3.37–3.46 (m, 2 H), 3.62–3.76 (m, 2 H), 3.66 (dd, J = 11.9, 7.8
Hz, 1 H), 4.00 (dd, J = 11.9, 4.1 Hz, 1 H), 4.10–4.26 (m, 1 H).
2-(2-Methoxyphenyl)-5,6,7,7a-tetrahydro-1H-pyrrolo[1,2-
c]imidazol-2-ium Hexafluorophosphate (6g)
Brown solid; yield: 398 mg (1.10 mmol, 22%); mp 154 °C.
[α]D25 –155.4 (c 1.20, CH2Cl2).
Synthesis 2014, 46, 242–250
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Synthesis and Characterization of New Chiral Azolinium Salts
247
13C NMR (75 MHz, CD3OD): δ = 24.1, 27.0, 30.0, 34.2, 46.7, 50.7,
[α]D20 –207.9 (c 0.95, MeOH).
57.8, 58.9, 71.6.
IR (neat): 3248, 2965, 1621, 2878 cm–1.
HRMS (ESI): m/z [M + H]+ calcd for C11H25N2O: 201.1967; found:
201.1961.
1H NMR (360 MHz, CD3OD): δ = 1.01 (dd, J = 10.5, 6.6 Hz, 6 H),
1.57–1.82 (m, 1 H), 1.91–2.34 (m, 4 H), 3.43–3.62 (m, 2 H), 3.66–
3.77 (m, 1 H), 3.78–3.90 (m, 2 H), 3.91–4.00 (m, 1 H), 4.07 (dd, J =
11.7, 11.0 Hz, 1 H), 4.33–4.54 (m, 1 H), 8.46 (s, 1 H).
13C NMR (90 MHz, CD3OD): δ = 19.5, 20.1, 25.3, 28.8, 31.3, 46.7,
52.0, 59.7, 64.6, 68.4, 161.2.
(R)-2-Phenyl-2-[(S)-pyrrolidin-2-ylmethylamino]ethanol Hy-
drochloride (10d)
White solid; yield: 768 mg (3.00 mmol, 91%).
[α]D20 –8.3 (c 1.0, MeOH).
IR (neat): 3314, 2940, 2739, 2485, 1413, 1043 cm–1.
1H NMR (360 MHz, CD3OD): δ = 1.67–1.86 (m, 1 H), 1.94–2.17
(m, 2 H), 2.23–2.41 (m, 1 H), 3.18 (dd, J = 13.6, 5.3 Hz, 1 H), 3.39
(dd, J = 8.2, 6.6 Hz, 2 H), 3.56–3.67 (m, 1 H), 3.94–4.15 (m, 3 H),
4.52 (dd, J = 7.2, 4.5 Hz, 1 H), 7.41–7.54 (m, 3 H), 7.56–7.70 (m, 2
H).
13C NMR (90 MHz, CD3OD): δ = 24.1, 30.0, 46.9, 47.7, 58.0, 63.3,
65.0, 129.7, 130.6, 131.1, 133.9.
HRMS (ESI): m/z [M]+ calcd for C11H21N2O: 197.1648; found:
197.1648.
(S)-2-[(S)-1-Hydroxy-3,3-dimethylbutan-2-yl]-5,6,7,7a-tetra-
hydro-1H-pyrrolo[1,2-c]imidazol-2-ium Chloride (11c)
Yellow paste; yield: 211 mg (0.85 mmol, 44%).
[α]D20 –177.96 (c 0.93, MeOH).
IR (neat): 3303, 3153, 2958, 1665, 1615, 1060 cm–1.
1H NMR (360 MHz, CD3OD): δ = 1.02 (s, 9 H), 1.55–1.78 (m, 1 H),
1.95–2.29 (m, 3 H), 3.47–3.63 (m, 2 H), 3.71–3.95 (m, 3 H), 4.00
(dd, J = 12.4, 6.1 Hz, 1 H), 4.15 (dd, J = 11.2, 6.4 Hz, 1 H), 4.36–
4.52 (m, 1 H), 8.46 (s, 1 H).
13C NMR (90 MHz, CD3OD): δ = 25.1, 27.6, 31.3, 34.7, 46.9, 53.4,
57.7, 65.1, 71.6, 162.4.
HRMS (ESI): m/z [M + H]+ calcd for C13H21N2O: 221.1654; found:
221.1648.
(S)-3-Phenyl-2-[(S)-pyrrolidin-2-ylmethylamino]propan-1-ol
Hydrochloride (10e)
Yellow solid; yield: 648 mg (2.40 mmol, 72%).
[α]D20 –30.10 (c 0.99, MeOH).
IR (neat): 3300, 2949, 2739, 2356, 1413, 1054 cm–1.
HRMS (ESI): m/z [M]+ calcd for C12H23N2O: 211.1805; found:
211.1796.
1H NMR (360 MHz, CD3OD): δ = 1.81–1.96 (m, 1 H), 1.99–2.24
(m, 2 H), 2.29–2.48 (m, 1 H), 2.96–3.09 (m, 1 H), 3.24 (dd, J = 13.9,
4.2 Hz, 1 H), 3.39–3.49 (m, 2 H), 3.53–3.63 (m, 3 H), 3.68 (dd, J =
13.7, 7.5 Hz, 1 H), 3.72–3.83 (m, 1 H), 3.97–4.14 (m, 1 H), 7.22–
7.37 (m, 5 H).
13C NMR (90 MHz, CD3OD): δ = 24.2, 30.0, 35.0, 46.9, 47.0, 58.0,
58.1, 63.1, 128.4, 129.9, 130.5, 136.8.
(S)-2-[(R)-2-Hydroxy-1-phenylethyl]-5,6,7,7a-tetrahydro-1H-
pyrrolo[1,2-c]imidazol-2-ium Chloride (11d)
Yellow paste; yield: 176 mg (0.66 mmol, 34%).
[α]D20 –257.9 (c 0.95, MeOH).
IR (neat): 3223, 2930, 2881, 1610, 1056 cm–1.
1H NMR (300 MHz, CD2Cl2): δ = 1.62–1.85 (m, 1 H), 1.90–2.32
(m, 4 H), 3.51 (dd, J = 11.4, 9.8 Hz, 1 H), 3.61 (dd, J = 11.7, 6.1 Hz,
1 H), 3.82–4.01 (m, 2 H), 4.09–4.41 (m, 3 H), 4.93 (dd, J = 10.1, 3.7
Hz, 1 H), 7.20–7.55 (m, 5 H), 9.56 (s, 1 H).
HRMS (ESI): m/z [M + H]+ calcd for C14H23N2O: 235.1810; found:
235.1805.
(S)-2-(2-Hydroxyethyl)-5,6,7,7a-tetrahydro-1H-pyrrolo[1,2-
c]imidazol-2-ium Hexafluorophosphate (11a)
13C NMR (75 MHz, CD2Cl2): δ = 25.2, 30.8, 46.5, 62.1, 63.6, 65.9,
127.9, 129.7, 129.8, 134.8, 159.8.
A mixture of diamine 10a (1.08 mmol), NH4PF6 (1.14 mmol, 1.05
equiv), and trimethyl orthoformate (5.41 mmol, 5 equiv) was sub-
jected to microwave irradiation at 100 °C for 5 min. After cooling
to r.t., the solvent was evaporated. The residue was purified by flash
chromatography (silica gel, CH2Cl2–MeOH, 80:20) to give the pure
salt 11a as a yellow oil; yield: 96 mg (0.32 mmol, 30%).
[α]D20 –144.6 (c 0.97, MeOH).
IR (neat): 3596, 3368, 3069, 2967, 1634 cm–1.
1H NMR (360 MHz, CD3OD): δ = 1.59–1.84 (m, 1 H), 1.90–2.34
(m, 3 H), 3.44–3.60 (m, 2 H), 3.62–3.72 (m, 1 H), 3.72–3.84 (m, 3
H), 3.85–3.94 (m, 1 H), 4.04–4.22 (m, 1 H), 4.32–4.50 (m, 1 H),
8.16 (s, 1 H).
13C NMR (90 MHz, CD3OD): δ = 25.4, 31.0, 46.5, 51.7, 54.4, 58.9,
65.0, 160.8.
HRMS (ESI): m/z [M]+ calcd for C14H19N2O: 231.1492; found:
231.1482.
(S)-2-[(S)-1-Hydroxy-3-phenylpropan-2-yl]-5,6,7,7a-tetra-
hydro-1H-pyrrolo[1,2-c]imidazol-2-ium Hexafluorophosphate
(11e)
A mixture of diamine hydrochloride 10e (1.14 mmol) and trimethyl
orthoformate (11.4 mmol, 10 equiv) in toluene (3.50 mL) was heat-
ed at 100 °C for 15 h. The solution was cooled to r.t., and the solvent
was evaporated under reduced pressure. The residue was dissolved
in H2O (5 mL), and washed with EtOAc (2 × 10 mL) before addition
of KPF6 (1.48 mmol, 1.3 equiv). After stirring the mixture at r.t. for
20 min, a brown oil was observed. The aqueous layer was extracted
with CH2Cl2 (3 × 10 mL), washed with brine and dried (Na2SO4).
The solvent was removed under reduced pressure, and the crude oil
was purified by preparative TLC to afford pure 11e as a yellow oil;
yield: 82 mg (0.21 mmol, 18%).
HRMS (ESI): m/z [M]+ calcd for C8H15N2O: 157.1179; found:
157.1175.
[α]D20 –248.4 (c 0.95, CH2Cl2).
IR (neat): 3583, 3055, 2986, 1625 cm–1.
Synthesis of Salts 11b–d; General Procedure
A mixture of diamine hydrochloride 10 (1.93 mmol) and trimethyl
orthoformate (9.64 mmol, 5 equiv) was subjected to microwave ir-
radiation at 100 °C for 5 min. After cooling to r.t., the solvent was
evaporated. The residue was purified by flash chromatography (sil-
ica gel, CH2Cl2–MeOH, 80:20) to afford the pure salt 11.
1H NMR (250 MHz, CD2Cl2): δ = 1.20–1.52 (m, 1 H), 1.62–2.15
(m, 3 H), 2.75 (dd, J = 14.0, 9.4 Hz, 1 H), 2.87 (dd, J = 14, 6.0 Hz,
1 H), 3.16–3.32 (m, 1 H), 3.46–3.67 (m, 3 H), 3.74 (dd, J = 12.1, 3.7
Hz, 1 H), 3.79–3.93 (m, 2 H), 3.99–4.25 (m, 1 H), 6.94–7.10 (m, 5
H), 7.56 (s, 1 H).
13C NMR (75 MHz, CD2Cl2): δ = 24.6, 30.4, 35.5, 46.0, 51.7, 61.3,
62.7, 63.5, 127.7, 129.2, 129.5, 136.3, 158.6.
(S)-2-[(S)-1-Hydroxy-3-methylbutan-2-yl]-5,6,7,7a-tetrahydro-
1H-pyrrolo[1,2-c]imidazol-2-ium Chloride (11b)
Yellow oil; yield: 206 mg (0.89 mmol, 46%).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 242–250

248
A. Thomasset et al.
PAPER
HRMS (ESI): m/z [M]+ calcd for C15H21N2O: 245.1648; found:
245.1645.
1H NMR (250 MHz, CDCl3): δ = 1.15–1.40 (m, 1 H), 1.73–2.17 (m,
3 H), 3.22–3.44 (m, 2 H), 3.65 (dd, J = 10.3, 9.4 Hz, 1 H), 3.75–3.93
(m, 1 H), 3.98–4.20 (m, 1 H), 4.81 (d, J = 4.8 Hz, 2 H), 7.14–7.57
(m, 5 H).
13C NMR (75 MHz, CDCl3): δ = 24.8, 31.0, 48.4, 51.1, 51.5, 59.6,
127.8, 128.1, 128.8, 136.3, 186.2.
Synthesis of NHC Dimers 12; General Procedure
In a glovebox, a Schlenk tube was charged with the appropriate salt
6 (1.08 mmol) and t-BuOK (1.19 mmol, 1.1 equiv). THF was added,
and the mixture was stirred at r.t. for 45 min. The solvent was evap-
orated under reduced pressure, before the addition of hexane. The
residue was filtered, and washed with hexane to afford the NHC di-
mer.
(S)-2-(2,6-Diisopropylphenyl)tetrahydro-1H-pyrrolo[1,2-c]im-
idazole-3(2H)-thione (13c)
Yield: 33 mg (0.11 mmol, 95%); mp 148 °C.
[α]D20 –105.1 (c 1.03, CH2Cl2).
(7aS,7′aS,E)-2,2′-Diphenyl-1,1′,2,2′,5,5′,6,6′,7,7′,7a,7′a-dodeca-
hydro-3,3′-bipyrrolo[1,2-c]imidazolylidene (12a)
Yellow oil; yield: 335 mg (0.90 mmol, 84%).
1H NMR (360 MHz, THF-d8): δ = 1.47–1.82 (m, 2 H), 1.83–2.13
(m, 2 H), 2.32–2.58 (m, 1 H), 3.16–3.41 (m, 2 H), 3.61–3.95 (m, 2
H), 6.08–6.26 (m, 1 H), 6.32–6.48 (m, 1 H), 6.53–6.68 (m, 1 H),
6.69–6.93 (m, 1 H), 6.98–7.20 (m, 1 H).
13C NMR (90 MHz, THF-d8): δ = 27.1, 30.7, 31.0, 53.1, 53.5, 57.1,
58.1, 61.2, 61.3, 117.5, 117.7, 118.0, 121.8, 122.0, 127.7, 128.5,
144.6, 144.9.
IR (neat): 2960, 2927, 2869, 1475, 1419, 1376, 1346, 1259, 1099
cm–1.
1H NMR (360 MHz, CDCl3): δ = 1.22 (d, J = 7.0 Hz, 6 H), 1.29 (dd,
J = 6.9, 2.7 Hz, 6 H), 1.45–1.66 (m, 1 H), 1.85–2.01 (m, 1 H), 2.04–
2.20 (m, 2 H), 2.75–2.99 (m, 2 H), 3.4 (dd, J = 11.8, 9.4 Hz, 1 H),
3.67 (dd, J = 10.4, 3.7 Hz, 1 H), 3.94 (dd, J = 10.3, 9.3 Hz, 1 H),
4.02–4.13 (m, 1 H), 4.14–4.26 (m, 1 H), 7.14–4.24 (m, 2 H), 7.31–
7.45 (m, 1 H).
13C NMR (90 MHz, CDCl3): δ = 24.4, 24.9, 28.6, 31.5, 48.7, 55.4,
60.5, 124.2, 124.7, 129.3, 143.3, 147.2, 147.4, 187.6.
HRMS (ESI): m/z [M]+ calcd for C18H26N2S: 302.1817; found:
302.1889.
(7aS,7′aS,E)-2,2′-Dibenzyl-1,1′,2,2′,5,5′,6,6′,7,7′,7a,7′a-dodeca-
hydro-3,3′-bipyrrolo[1,2-c]imidazolylidene (12b)
Yellow powder; yield: 332 mg (0.83 mmol, 77%).
1H NMR (360 MHz, THF-d8): δ = 1.40–1.59 (m, 1 H), 1.61–1.73
(m, 1 H), 1.75–1.93 (m, 2 H), 2.64–2.78 (m, 1 H), 2.85–2.96 (m, 1
H), 2.99–3.23 (m, 2 H), 3.47–3.57 (m, 1 H), 3.71 (d, J = 14.0 Hz, 1
H), 4.43 (d, J = 14.0 Hz, 1 H), 7.06–7.46 (m, 5 H).
13C NMR (90 MHz, THF-d8): δ = 26.1, 31.0, 55.2, 55.9, 56.9, 61.7,
127.1, 128.7, 129.3, 130.5, 141.8.
(S)-2-[(R)-1-Phenylethyl]tetrahydro-1H-pyrrolo[1,2-c]imidaz-
ole-3(2H)-thione (13e)
Yield: 15 mg (0.06 mmol, 48%); mp 93 °C.
[α]D20 +35.44 (c 1.03, CH2Cl2).
IR (neat): 2971, 2928, 2878, 1490, 1433, 1381, 1291, 1097 cm–1.
1H NMR (250 MHz, CDCl3): δ = 1.19–1.48 (m, 1 H), 1.58 (d, J =
7.1 Hz, 3 H), 1.70–2.18 (m, 3 H), 3.14–3.51 (m, 3 H), 3.64–3.94 (m,
1 H), 3.99–4.30 (m, 1 H), 5.98–6.27 (m, 1 H), 7.18–7.52 (m, 5 H).
(7aS,7′aS,E)-2,2′-Bis(2,6-diisopropylphenyl)-
1,1′,2,2′,5,5′,6,6′,7,7′,7a,7′a-dodecahydro-3,3′-bipyrrolo[1,2-
c]imidazolylidene (12c)
13C NMR (75 MHz, CDCl3): δ = 15.4, 24.7, 31.0, 46.7, 48.2, 53.7,
Yellow oil; yield: 556 mg (1.03 mmol, 95%).
1H NMR (360 MHz, THF-d8): δ = 1.05–1.40 (m, 16 H), 1.86–2.19
(m, 2 H), 2.99–3.20 (m, 1 H), 3.23–3.44 (m, 2 H), 3.48–3.72 (m, 1
H), 3.80–4.06 (m, 1 H), 6.86–7.49 (m, 3 H).
59.4, 127.2, 127.7, 128.6, 139.8, 185.4.
HRMS (ESI): m/z [M]+ calcd for C14H18N2S: 246.1191; found:
246.1083.
13C NMR (90 MHz, THF-d8): δ = 23.4, 24.0, 24.4, 25.0, 25.3, 25.5,
25.6, 25.8, 26.0, 26.1, 26.6, 26.8, 28.6, 28.7, 29.0, 29.7, 31.0, 31.2,
52.7, 57.9, 59.4, 60.5, 62.0, 62.4, 123.3, 123.8, 124.1, 124.7, 126.4,
127.0, 127.7, 138.7, 141.8, 148.4, 149.9, 150.7, 152.3.
Synthesis of [Rh-NHC] Complexes; General Procedure
In a glovebox, a Schlenk tube was charged with NHC dimer (0.24
mmol) and [Rh(cod)Cl]2 (0.24 mmol, 1 equiv) in dry THF (2 mL).
The resulting mixture was stirred at r.t. for 24 h. The tube was re-
moved from the glovebox, and the solvent was evaporated under re-
duced pressure. The residue was purified by flash chromatography
(silica gel, pentane–EtOAc, 8:2) to afford the pure [Rh-NHC] com-
plex as a solid.
(7aS,7′aS,E)-2,2′-Bis[(R)-1-phenylethyl]-
1,1′,2,2′,5,5′,6,6′,7,7′,7a,7′a-dodecahydro-3,3′-bipyrrolo[1,2-
c]imidazolylidene (12e)
Orange solid; yield: 428 mg (1.00 mmol, 93%).
1H NMR (360 MHz, C6D6): δ = 1.19–1.30 (m, 1 H), 1.45–1.72 (m,
7 H), 2.43–2.62 (m, 1 H), 2.98–3.23 (m, 2 H), 3.24–3.36 (m, 1 H),
4.98–5.27 (m, 1 H,), 6.99–7.33 (m, 3 H), 7.36–7.53 (m, 2 H).
13C NMR (90 MHz, C6D6): δ = 20.9, 25.7, 30.5, 51.6, 53.9, 55.5,
61.2, 126.6, 127.8, 128.3, 129.3, 144.8.
Complex [Rh-NHC] 14b
Yellow solid; yield: 58 mg (0.13 mmol, 55%); mp 180 °C. X-ray
diffraction (Figure 1).
[α]D20 –44.11 (c 1.07, CH2Cl2).
1H NMR (250 MHz, CDCl3): δ = 1.33–1.52 (m, 1 H), 1.70–2.06 (m,
6 H), 2.07–2.59 (m, 5 H), 3.15 (dd, J = 10.5, 4.7 Hz, 1 H), 3.29–3.53
(m, 3 H), 3.57–3.69 (m, 1 H), 3.70–3.89 (m, 1 H), 4.75–4.89 (m, 1
H), 4.91–5.11 (m, 2 H), 5.20–5.54 (m, 2 H), 7.27–7.55 (m, 5 H).
13C NMR (75 MHz, CDCl3): δ = 24.7, 28.6, 29.2, 31.4, 32.7, 33.5,
47.7, 53.5, 55.0, 63.4, 66.6, 70.7, 99.5, 99.9, 127.9, 128.4, 128.9,
136.5, 217.8.
Synthesis of Thiones 13; General Procedure
In a glovebox, a Schlenk tube was charged with NHC dimer 12
(0.12 mmol) and sulfur (0.35 mmol, 2.9 equiv). C6D6 (1.5 mL) was
added, and the resulting mixture was stirred for 2 h at r.t. The mix-
ture was removed from the glovebox, and the solvent was evaporat-
ed under reduced pressure. The residue was purified by flash
chromatography (silica gel, pentane–EtOAc, 6:1) to give the pure
compound as white crystals.
HRMS (ESI): m/z [M]+ calcd for C21H28N2Rh: 411.1302; found:
411.1321.
(S)-2-Benzyltetrahydro-1H-pyrrolo[1,2-c]imidazole-3(2H)-thi-
one (13b)
Complex [Rh-NHC] 14c
Yellow solid; yield: 21 mg (0.04 mmol, 18%); mp 245 °C.
The thione 13b was described in literature. Spectral data of this
compound were in accordance with reported values.15b
[α]D20 –117.4 (c 0.55, CH2Cl2).
Yield: 16 mg (0.07 mmol, 59%).
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Synthesis and Characterization of New Chiral Azolinium Salts
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1H NMR (300 MHz, CDCl3): δ = 1.11 (d, J = 7.0 Hz, 3 H), 1.16–
1.27 (m, 6 H), 1.36–1.45 (m, 2 H), 1.49 (d, J = 6.4 Hz, 2 H), 1.54–
1.61 (m, 2 H), 1.80–2.21 (m, 8 H), 2.25–2.49 (m, 1 H), 2.64–2.76
(m, 1 H), 2.78–2.94 (m, 1 H), 3.23–3.37 (m, 1 H), 3.41–3.73 (m, 2
H), 3.74–3.90 (m, 2 H), 3.95–4.17 (m, 1 H), 4.66–4.81 (m, 1 H),
4.82–5.23 (m, 2 H), 7.05–7.22 (m, 1 H), 7.28–7.50 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 23.2, 23.4, 24.7, 24.8, 25.6, 26.7,
27.0, 27.6, 28.3, 29.5, 31.1, 31.6, 34.5, 46.6, 48.9, 58.3, 59.4, 62.5,
62.7, 66.1, 66.4, 67.4, 68.7, 98.02, 98.6, 99.3, 99.6, 123.6, 124.9,
125.2, 128.9, 129.0, 135.6, 135.9, 145.1, 147.0, 149.0, 149.2, 214.3.
(6) Dalko, P.; Moisan, L. Angew. Chem. Int. Ed. 2004, 43, 5138.
(7) (a) Wasserscheid, P.; Keim, W. Angew. Chem. Int. Ed. 2000,
39, 3772. (b) Dupont, J.; De Souza, R. F.; Suarez, P. A.
Chem. Rev. 2002, 102, 3667. (c) Wasserscheid, P.; Welton,
T. Ionic Liquids in Synthesis, 2nd ed.; Wiley-VCH:
Weinheim, 2008. (d) Deetlefs, M.; Seddon, K. S. Green
Chem. 2003, 5, 181. (e) Lévêque, J. M.; Estager, J.; Draye,
M.; Cravotto, G.; Boffa, L.; Bonrath, W. Monatsh. Chem.
2007, 138, 1103. (f) Aupoix, A.; Pégot, B.; Vo-Thanh, G.
Tetrahedron 2010, 66, 1352. (g) Pârvulescu, V. I.; Hardacre,
C. Chem. Rev. 2007, 107, 2615. (h) Van Rantwijk, F.;
Sheldon, R. A. Chem. Rev. 2007, 107, 2757. (i) Greaves, T.
L.; Drummond, C. J. Chem. Rev. 2008, 108, 206. (j) Martins,
M. A. P.; Frizzo, C. P.; Moreira, D. N.; Zanatta, N.;
Bonacorso, H. G. Chem. Rev. 2008, 108, 2015. (k) Aupoix,
A.; Vo-Thanh, G. Synlett 2009, 1915.
HRMS (ESI): m/z [M]+ calcd for C26H38N2Rh: 481.2090; found:
481.2115.
Complex [Rh-NHC] 14e
Yellow solid; yield: 41 mg (0.09 mmol, 37%); mp 172 °C. X-ray
diffraction (Figure 2).
(8) Saba, S.; Brescia, A.; Kaloustian, M. A. Tetrahedron Lett.
1991, 32, 5031.
[α]D20 –57.3 (c 0.52, CH2Cl2).
1H NMR (300 MHz, CDCl3): δ = 1.35–1.53 (m, 1 H), 1.72 (d, J =
7.0 Hz, 3 H), 1.77–2.58 (m, 11 H), 3.22–3.35 (m, 2 H), 3.36–3.48
(m, 2 H), 3.58–3.69 (m, 1 H), 3.69–3.80 (m, 1 H), 4.79–4.89 (m, 1
H), 4.90–5.14 (m, 2 H), 6.47–6.69 (m, 1 H), 7.27–7.51 (m, 5 H).
13C NMR (100 MHz, CDCl3): δ = 17.8, 24.6, 28.3, 29.6, 31.6, 32.2,
33.9, 48.1, 49.3, 58.2, 62.6, 66.0, 71.4, 99.3, 99.9, 127.1, 127.6,
128.8, 141.4, 217.3.
(9) (a) Arduengo, A. J.; Krafczyk, R.; Schmutzler, R.; Craig, H.
A.; Goerlich, J. R.; Marshall, W. J.; Unverzagt, M.
Tetrahedron 1999, 55, 14523. (b) Ma, Y.; Song, C.; Jiang,
W.; Wu, Q.; Wang, Y.; Liu, X.; Andrus, M. B. Org. Lett.
2003, 5, 3317. (c) Funk, T. W.; Berlin, J. M.; Grubbs, R. H.
J. Am. Chem. Soc. 2006, 128, 1840. (d) Alder, R. W.; Blake,
M. E.; Bufali, S.; Butts, C. P.; Orpen, A. G.; Schütz, J.;
Williams, S. J. J. Chem. Soc., Perkin Trans. 1 2001, 1586.
(e) Van Veldhuizen, J. J.; Gillingham, D. G.; Garber, S. B.;
Kataoka, O.; Hoveyda, A. H. J. Am. Chem. Soc. 2003, 125,
12502.
HRMS (ESI): m/z [M]+ calcd for C22H30N2Rh: 425.1464; found:
425.1489.
(10) Aidouni, A.; Bendahou, S.; Demonceau, A.; Delaude, L.
J. Comb. Chem. 2008, 10, 886.
(11) Rix, D.; Labat, S.; Toupet, L.; Crévisy, C.; Mauduit, M. Eur.
J. Inorg. Chem. 2009, 1989.
Acknowledgment
We wish to thank the French Ministry of Education and Research
(MENESR) for a doctoral fellowship to Amélia Thomasset, the
CNRS and the University of Paris-Sud for financial supports.
(12) (a) Vo-Thanh, G.; Pégot, B.; Loupy, A. Eur. J. Org. Chem.
2004, 1112. (b) Varma, R. S.; Namboodiri, V. V. Chem.
Commun. 2001, 643. (c) Varma, R. S.; Namboodiri, V. V.
Pure Appl. Chem. 2001, 73, 1309. (d) Khadilkar, B. M.;
Rebeiro, G. L. Org. Process Res. Dev. 2002, 6, 826. (e) Law,
M. C.; Wong, K. Y.; Chan, T. H. Green Chem. 2002, 4, 328.
(f) Varma, R. S.; Namboodiri, V. V. Chem. Commun. 2002,
342. (g) Dubreuil, J. F.; Famelart, M. H.; Bazureau, J. P.
Org. Process Res. Dev. 2002, 6, 374. (h) Cravotto, G.;
Calcio-Gaudino, E.; Boffa, L.; Lévêque, J. M.; Estager, J.;
Bonrath, W. Molecules 2008, 13, 149.
(13) For reviews on microwave chemistry, see: (a) Perreux, L.;
Loupy, A. Tetrahedron 2001, 57, 9199. (b) Lidström, P.;
Tierney, J.; Wathey, P.; Westman, J. Tetrahedron 2001, 57,
9225. (c) Hayes, B. L. Microwave Synthesis: Chemistry at
the Speed of Light; CEM Publishing: Matthews NC, 2002.
(d) Loupy, A. Microwaves in Organic Synthesis; Wiley-
VCH: Weinheim, 2006. (e) Kappe, C. O.; Stadler, A.
Microwaves in Organic and Medicinal Chemistry; Wiley-
VCH: Weinheim, 2005. (f) Polshettiwar, V.; Varma, R. S.
Acc. Chem. Res. 2008, 41, 629. (g) Truong, T. K. T.; Nguyen
Van Buu, O.; Pégot, B.; Aupoix, A.; Vo-Thanh, G. Curr.
Org. Synth. 2012, 1, 53.
(14) (a) Zhang, J.; Qin, X.; Fu, J.; Wang, X.; Su, X.; Hu, F.; Jiao,
J.; Shi, M. Organometallics 2012, 31, 8275. (b) Makhloufi,
A.; Wahl, M.; Frank, W.; Ganter, C. Organometallics 2013,
32, 854.
(15) (a) Xu, J.; Fu, X.; Wu, C.; Hu, X. Tetrahedron: Asymmetry
2011, 22, 840. (b) Held, I.; Larionov, E.; Bozler, C.;
Wagner, F.; Zipse, H. Synthesis 2009, 2267. (c) Kikuchi, M.;
Inagaki, T.; Nishimaya, H. Synlett 2007, 1075. (d) Fuentes
de Arriba, A. L.; Simon, L.; Raposo, C.; Alcazar, V.; Moran,
J. R. Tetrahedron 2009, 65, 4841. (e) Kelleher, F.; Kelly, S.;
Watts, J.; McKee, V. Tetrahedron 2010, 66, 3525.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
nnfomartit
References
(1) (a) Arduengo, A. J.; Harlow, R. L.; Kline, M. J. Am. Chem.
Soc. 1991, 113, 361. (b) Fröhlich, N.; Pidun, U.; Stahl, M.;
Frenking, G. Organometallics 1997, 16, 442. (c) Herrmann,
W. A. Angew. Chem. Int. Ed. 2002, 41, 1290. (d) Hahn, F. E.
Angew. Chem. Int. Ed. 2006, 45, 1348. (e) Jacobsen, H.;
Correa, A.; Poater, A.; Costabile, C.; Cavallo, L. Coord.
Chem. Rev. 2009, 253, 687. (f) Diez-Gonzalez, S.; Marion,
N.; Nolan, S. P. Chem. Rev. 2009, 109, 3612.
(g) Samojłowicz, C.; Bieniek, M.; Grela, K. Chem. Rev.
2009, 109, 3708.
(2) Bourissou, D.; Guerret, O.; Gabbaï, F. P.; Bertrand, G.
Chem. Rev. 2000, 100, 39.
(3) (a) Lee, H. M.; Lee, C. C.; Cheng, P. J. Curr. Org. Chem.
2007, 11, 1491. (b) Dröge, T.; Glorius, F. Angew. Chem. Int.
Ed. 2010, 49, 6940. (c) Benhamou, L.; Chardon, E.;
Lavigne, G.; Bellemin-Laponnaz, S.; César, V. Chem. Rev.
2011, 111, 2705.
(4) (a) Zinner, S. C.; Herrmann, W. A.; Kuhn, F. E.
J. Organomet. Chem. 2008, 693, 1543. (b) Perry, M. C.;
Burgess, K. Tetrahedron: Asymmetry 2003, 14, 951.
(c) César, V.; Bellemin-Laponnaz, S.; Gade, L. H. Chem.
Soc. Rev. 2004, 33, 619. (d) Glorius, F. N-Heterocyclic
Carbenes in Transition Metal Catalysis; Springer: Berlin,
2007.
(5) Aupoix, A.; Bournaud, C.; Vo-Thanh, G. Eur. J. Org. Chem.
2011, 2772.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 242–250

250
A. Thomasset et al.
PAPER
(f) Carmona, A.; Corma, A.; Iglesias, M.; San José, A.;
Sanchez, F. J. Organomet. Chem. 1995, 492, 11.
Tetrahedron: Asymmetry 2002, 13, 2229. (j) Miao, S.; Bai,
J.; Yang, J.; Zhang, Y. Chirality 2010, 22, 855.
(g) Clapham, B.; Wilson, N. S.; Michmerhuizen, M. J.;
Blanchard, D. P.; Dingle, D. M.; Nemcek, T. A.; Pan, J. Y.;
Sauer, D. R. J. Comb. Chem. 2008, 10, 88. (h) Asami, M.;
Ohno, H.; Kobayashi, S.; Mukaiyama, T. Bull. Chem. Soc.
Jpn. 1978, 51, 1869. (i) Amedjkouh, M.; Ahlberg, P.
(16) (a) Tang, Z.; Jiang, F.; Cui, X.; Gong, L.-Z.; Mi, A.-Q.;
Jiang, Y.-Z.; Wu, Y.-D. Proc. Natl. Acad. Sci. U.S.A. 2004,
101, 5755. (b) Almaşi, D.; Alonso, D. A.; Gómez-Bengoa,
E.; Nagel, Y.; Nájera, C. Eur. J. Org. Chem. 2007, 2328.
(17) CEM Discover S class reactor, see www.cem.com.
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