Imidazolinium and amidinium salts as Lewis acid organocatalysts

Article abstract of DOI:10.3762/bjoc.8.205

The application of imidazolinium and amidinium salts as soft Lewis acid organocatalysts is described. These salts were suitable catalysts for the activation of unsaturated thioesters in a Diels-Alder reaction and in the ring opening of thiiranes and epoxi

Full text of DOI:10.3762/bjoc.8.205

Imidazolinium and amidinium salts as
Lewis acid organocatalysts
Oksana Sereda1, Nicole Clemens1, Tatjana Heckel2 and René Wilhelm*1,2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2012, 8, 1798–1803.
1Institute of Organic Chemistry, Clausthal University of Technology,
38678 Clausthal-Zellerfeld, Germany and 2Department of Chemistry,
University of Paderborn, 33098 Paderborn, Germany
doi:10.3762/bjoc.8.205
Received: 30 May 2012
Accepted: 17 September 2012
Published: 18 October 2012
Email:
René Wilhelm* - rene.wilhelm@uni-paderborn.de
This article is part of the Thematic Series "Organocatalysis".
Guest Editor: B. List
* Corresponding author
Keywords:
Diels–Alder; ionic liquids; organocatalysis; soft Lewis acids; thiiranes;
thioesters
© 2012 Sereda et al; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
The application of imidazolinium and amidinium salts as soft Lewis acid organocatalysts is described. These salts were suitable
catalysts for the activation of unsaturated thioesters in a Diels–Alder reaction and in the ring opening of thiiranes and epoxides. The
products were isolated in good yields. The mild catalysts did not cause desulfurization of the products containing a thiol or thiocar-
bonyl group.
Introduction
Salts with melting points below 100 °C are known as ionic Recently, we applied saturated imidazolium salts with an aryl
liquids and are often used as novel solvents for reactions and substituent at the C(2) position as catalysts for the aza-
electrochemical processes [1]. Several of these solvents can Diels–Alder reaction [11,12]. These catalysts do not activate the
contribute to the research field of “green chemistry” [2]. The substrate through hydrogen bonding, but instead, like other
most common used ionic liquids are based on imidazolium carbon-cation based catalysts, through their positive center
cations. Next to their application in catalytic reactions [3-6], [8-10,13-15], and belong also to the field of organocatalysis
they are also capable of catalyzing reactions themselves, either [10,16,17].
in substoichiometric amounts or as reaction medium due to
hydrogen-bond activation of the protons of the imidazolium Taking the soft Lewis acidic character of imidazolinium salts
cation [7-10] and other variables, such as π-orbital and into consideration, we were interested to apply these salts in a
charge–charge interactions [8-10].
Diels–Alder reaction with ethyl crotonthioate as dienophile.
1798

Beilstein J. Org. Chem. 2012, 8, 1798–1803.
Due to the low electronegativity of sulfur it would be difficult
to catalyze this reaction with hydrogen-bond activation cata-
lysts [18]. The utilization of the soft Lewis basic sulfur groups
in this reaction is rare. Often mercury Lewis acids are applied
[19-22] to activate the sulfur group and there is also the risk of
desulfurization [23].
The only known asymmetric Diels–Alder reaction with ethyl
crotonthioate (1) and cyclopentadiene (2) in the presence of
optically pure 2,2'-dimercurio-1,1'-binaphthyl compound 3 gave
the product 4 in 44% yield with 58% ee (Scheme 1) [20].
Scheme 1: Diels–Alder reaction with ethyl crotonthioate (1) and
cyclopentadiene (2).
Scheme 2: Diels–Alder reaction catalysed with imidazolinium salts.
Results and Discussion
First a few metal-based Lewis acids were applied in the reac-
Since product 4 has a low boiling point and proved difficult to tion. BF3•Et2O is known to activate also sulfur carbonyl groups
purify on a small scale, the model reaction shown in Scheme 2 [24] and gave the product in 90% yield, while TMSOTf gave
was evaluated. The α,β-unsaturated thioester 5 was prepared the product in 55% yield. In both cases the endo product was
from ethyl cinnamate and 2,4-bis(4-methoxyphenyl)-1,3,2,4- the major product. The reaction was followed by TLC and the
dithiadiphosphetane-2,4-disulfide (Lawesson’s reagent) [22]. temperature was gradually increased from –10 to 45 °C over 4
The cycloaddition of ethyl thionocinnamate (5) with 1.5 equiv days in ca. 10 °C steps.
of cyclopentadiene (2) was performed in different solvents, at
varied temperatures, by using a broad range of catalysts, which Next, imidazolinium salt 7 [25] was used in the reaction. The
are summarized in Table 1.
formation of the product was observed at 45 °C; however, the
Table 1: Diels–Alder reaction with 10 mol % catalyst according to Scheme 2. Reactions with CH2Cl2 were carried out in a pressure vessel.
entry
solvent
catalyst
temp [°C]
time [d]
yield %a (endo:exo)
1
2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
toluene
dioxane
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Hg(OAc)2
−10–45
−10–45
−10–45
25–45
25–110
25–110
25–45
0–45
4
4
4
4
4
4
4
4
4
3
0
BF3.Et2O
90 (99:1)
55 (99:1)
8 (13:1)
0
3
TMSOTf
4
7
7
5
6
7
6 (3:1)
7
8
5 (9:1)
8
9
12 (14:1)
69 (99:1)
66 (99:1)
9
10
11
−10–45
0–45
10
aIsolated yields.
1799

Beilstein J. Org. Chem. 2012, 8, 1798–1803.
product was isolated only in a low yield of 8%. In toluene no
reaction was observed even under reflux. In dioxane under
reflux a low yield of 6% was obtained with a low endo/exo ratio
of (3:1). Salt 8 [25] and 9 [25] gave similar poor results as
salt 7 [25]. Finally, the bis-imidazolinium salt 10 [12] gave the
product in 69% yield with an endo/exo ratio comparable to
BF3•Et2O. The reaction started slowly at 10 °C. In addition, the
similar salt 11 [12] gave the product in a comparable yield of
66%. Although in all cases the product was racemic, the results
show that bis-imidazolinium salts can be applied as Lewis acid
organocatalysts to activate a thiocarbonyl group.
Next, the behavior of these salts in the ring opening of a thiirane
was explored. No activity was observed with salt 9 in the ring
opening with aniline. Therefore, the more active bis-imida-
zolinium salt 10 was applied with thiirane 12 and aniline in
CH2Cl2. A yield of 18% was obtained. However, in the absence
of a solvent the yield increased to 98% after 16 h (Scheme 3). In
the absence of a catalyst a yield of 12% was obtained under neat
conditions. Product 13 was obtained in all reactions as race-
mate in the error range of the HPLC measurements.
Scheme 3: Ring opening of thiirane 12.
Scheme 4: Ring opening of epoxide 14.
Next, several salts were explored in the ring opening of cyclo-
hexene epoxide with aniline (Scheme 4, Table 2). A reaction in
CH2Cl2 in the absence of the catalyst gave a yield of 10% after
24 h (Table 2, entry 1).
Table 2: Ring opening of epoxide 15 with aniline and 10 mol % salt.
entry
solvent
catalyst
time
yield %a
The camphor based salt 16 gave a yield of 24%, while bis-
imidazolinium salt 17 resulted in a yield of 60% (Table 2,
entries 2 and 3). The bis-imidazolinium salts 10 and 11 gave
lower yields compared to 17. However, when the reaction was
carried out in the absence of a solvent, the yield increased with
salts 10 and 11 to 98 and 96%, respectively (Table 2, entries 6
and 7).
1
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
neat
–
24 h
24 h
48 h
48 h
48 h
24 h
24 h
24 h
48 h
24 h
24 h
6 h
10
24
60
34
48
98
96
0
2
16
17
10
11
10
11
–
3
4
5
6
7
neat
8
neat
9
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
toluene
toluene
18
19
20
21
–
12
78
38
99
0
Compared to sulfur, oxygen is a good hydrogen-bond acceptor.
Hence, also imidazolinium salts with a C(2)H unit were applied
in the reaction. Here, an activation of the epoxide can be also
possible through hydrogen bonding next to the direct inter-
action with the positively charged NCN center. While salt 18
displayed very low catalytic activity, salt 19 gave the product in
78% yield (Table 2, entry 10). This phenomenon may be
10
11
12
13
14
2 h
21
2 h
89
aIsolated yields.
1800

Beilstein J. Org. Chem. 2012, 8, 1798–1803.
Scheme 5: Synthesis of bis-imidazolium salt 17.
explained by the better delocalization of the positive charge in Salt 17 was prepared according to Scheme 5. The synthetic
the planar sp2-centered imidazoline scaffold in salt 18. Mean- route involved a tetraamine formation via amidation under neat
while the special geometry of 7-membered 1,3-diazepinium conditions and reduction with LAH, furnishing the product in
cations such as 19 does not allow the planar conformation to be 98% yield over two steps. Next, the aminal formation under
kept, thus the positive charge is less delocalized over the NCN neat conditions was performed. The aminal was further
atoms (Scheme 4) [26-29]. Salt 16, incorporating a six- oxidized to a bromide salt by N-bromoacetamide in
membered ring as the smallest ring, displayed a catalytic dimethoxyethane. The bromide counter anion was further
activity between salt 18 and 19. Salt 20, with a larger steric efficiently replaced by a tetrakis(3,5-bis(trifluoro-
environment around the amidinium unit next to the nitrogen methyl)phenyl)borate anion providing the salt 17 by anion
atoms, gave a yield of only 38% (Table 2, entry 11). On the metathesis.
other hand salt 21 gave the product in 99% yield after 6 h (Ta-
ble 2, entry 12). By changing the solvent from dichloromethane The 7-membered 1,3-diazepinium salts were prepared
to toluene the reaction time was even further reduced with salt according to Scheme 6. Salts 19 and 20 were prepared in a stan-
21, and the product was isolated in 89% yield (Table 2, entry dard way by treatment with triethyl orthoformate in the pres-
14). In all cases product 15 was racemic in the error range of the ence of ammonium tetrafluoroborate followed by anion
HPLC measurements.
metathesis in 33 and 29% yield, respectively.
Scheme 6: Synthesis of amidinium salt 21.
1801

Beilstein J. Org. Chem. 2012, 8, 1798–1803.
10.Sereda, O.; Tabasum, S.; Wilhelm, R. Top. Curr. Chem. 2010, 291,
349. doi:10.1007/128_2008_17
Due to the low yield, salt 21 was prepared through a different
route. First amine 27 [30] was transformed with formaldehyde
to the aminal 28. The latter could be oxidized to the corres-
ponding bromide salt, which was transformed directly by anion
metathesis to the salt 21.
See for a review.
11.Jurčík, V.; Wilhelm, R. Org. Biomol. Chem. 2005, 3, 239.
doi:10.1039/b415023f
12.Jurčík, V.; Wilhelm, R. Tetrahedron: Asymmetry 2006, 17, 801.
doi:10.1016/j.tetasy.2006.02.021
13.Mukaiyama, T.; Yanagisawa, M.; Iida, D.; Hachiya, I. Chem. Lett. 2000,
606. doi:10.1246/cl.2000.606
Conclusion
It was possible to prepare new metal-free Lewis acids
containing bis-imidazolinium cations and investigate the salts as
organocatalysts. Although with enantiopure chiral salts no enan-
tiomeric excess was observed, it was shown for the first time
that these salts can interact with thiocarbonyl groups and
thiiranes in order to activate these substrates. In addition, it was
found that 7-membered 1,3-diazepinium cations are good cata-
lysts for the ring opening of epoxides and that these salts are
more reactive than imidazolinium salts.
14.Chen, C.-T.; Chao, S.-D.; Yen, K.-C.; Chen, C. H.; Chou, I.-C.;
Hon, S.-W. J. Am. Chem. Soc. 1997, 119, 11341.
doi:10.1021/ja970900o
15.Chen, C.-T.; Chao, S.-D.; Yen, K.-C. Synlett 1998, 924.
doi:10.1055/s-1998-1815
16.Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 2001, 40, 3726.
doi:10.1002/1521-3773(20011015)40:20<3726::AID-ANIE3726>3.0.CO
;2-D
See for a review.
17.Berkessel, A.; Gröger, H. Asymmetric Organocatalysis; Wiley-VCH:
Weinheim, Germany, 2005.
See for a review.
Supporting Information
18.Wittkopp, A.; Schreiner, P. Chem.–Eur. J. 2003, 9, 407.
doi:10.1002/chem.200390042
Supporting Information File 1
Experimental part.
19.Lopez, P.; Oh, T. Tetrahedron Lett. 2000, 41, 2313.
doi:10.1016/S0040-4039(00)00157-X
20.Oh, T.; Lopez, P.; Reilly, M. Eur. J. Org. Chem. 2000, 2901.
doi:10.1002/1099-0690(200008)2000:16<2901::AID-EJOC2901>3.0.C
O;2-0
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-8-205-S1.pdf]
21.Lee, H.; Diaz, M.; Hawthorne, M. F. Tetrahedron Lett. 1999, 40, 7651.
doi:10.1016/S0040-4039(99)01582-8
Acknowledgements
Financial support by the DFG is gratefully acknowledged. In
addition, Dr. Dräger from the University of Hannover is
acknowledged for HRMS measurements.
22.Alper, H.; Brandes, D. A. Organometallics 1991, 10, 2457.
doi:10.1021/om00053a058
23.Wuest, J. D.; Zacharie, B. J. Am. Chem. Soc. 1985, 107, 6121.
doi:10.1021/ja00307a058
24.Braddock, D. C.; Brown, J. M.; Guiry, P. J.
J. Chem. Soc., Chem. Commun. 1993, 1244.
25.Clemens, N.; Sereda, O.; Wilhelm, R. Org. Biomol. Chem. 2006, 4,
2285. doi:10.1039/b601104g
References
1. Wasserscheid, P.; Welton, T., Eds. Ionic Liquids in Synthesis, 2nd ed.;
Wiley-VCH: Weinheim, Germany, 2008; Vol. 1–2.
2. Rogers, R. D.; Seddon, K. R., Eds. Ionic Liquids as Green Solvents:
Progress and Prospects; American Chemical Society: Washington, DC,
2003.
26.Alder, R. W.; Blake, M. E.; Oliva, J. M. J. Phys. Chem. A 1999, 103,
11200. doi:10.1021/jp9934228
27.Magill, A. M.; Cavell, K. J.; Yates, B. F. J. Am. Chem. Soc. 2004, 126,
8717. doi:10.1021/ja038973x
3. Zhao, D.; Wu, M.; Kou, Y.; Min, E. Catal. Today 2002, 74, 157.
doi:10.1016/S0920-5861(01)00541-7
28.Scarborough, C. C.; Popp, B. V.; Guzei, I. A.; Stahl, S. S.
J. Organomet. Chem. 2005, 690, 6143.
4. Baudequin, C.; Baudoux, J.; Levillain, J.; Cahard, D.; Gaumont, A.-C.;
Plaquevent, J.-C. Tetrahedron: Asymmetry 2003, 14, 3081.
doi:10.1016/S0957-4166(03)00596-2
doi:10.1016/j.jorganchem.2005.08.022
29.Iglesias, M.; Beetstra, D. J.; Knight, J. C.; Ooi, L.-L.; Stasch, A.;
Coles, S.; Male, L.; Hursthouse, M. B.; Cavell, K. J.; Dervisi, A.;
Fallis, I. A. Organometallics 2008, 27, 3279. doi:10.1021/om800179t
30.Angelovski, G.; Keränen, M. D.; Eilbracht, P. Tetrahedron: Asymmetry
2005, 16, 1919. doi:10.1016/j.tetasy.2005.03.035
5. Jain, N.; Kumar, A.; Chauhan, S.; Chauhan, S. M. S. Tetrahedron
2005, 61, 1015. doi:10.1016/j.tet.2004.10.070
6. Pârvulescu, V. I.; Hardacre, C. Chem. Rev. 2007, 107, 2615.
doi:10.1021/cr050948h
7. Aggarwal, A.; Lancaster, N. L.; Sethi, A. R.; Welton, T. Green Chem.
2002, 4, 517. doi:10.1039/b206472c
8. Vidiš, A.; Ohlin, C. A.; Laurenczy, G.; Küsters, E.; Sedelmeier, G.;
Dyson, P. J. Adv. Synth. Catal. 2005, 347, 266.
doi:10.1002/adsc.200404301
9. Tsuzuki, S.; Tokuda, H.; Mikami, M. Phys. Chem. Chem. Phys. 2007,
9, 4780. doi:10.1039/b707419k
1802

Beilstein J. Org. Chem. 2012, 8, 1798–1803.
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(http://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.8.205
1803