Fluorous tagging of DABCO through halogen bonding: Recyclable catalyst for the Morita-Baylis-Hillman reaction

Article abstract of DOI:10.1039/c1cc10869g

The halogen-bonded adduct between DABCO and two molecules of perfluorooctyl iodide (DABCO·(C₈F₁₇I)₂) acts as a recyclable organocatalyst for the Morita-Baylis-Hillman reaction. This "supramolecular fluorous catalyst" is re

Full text of DOI:10.1039/c1cc10869g

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COMMUNICATION
Fluorous tagging of DABCO through halogen bonding: recyclable
catalyst for the Morita–Baylis–Hillman reactionwz
Sophie Dordonne, Benoit Crousse, Daniele Bonnet-Delpon and Julien Legros*
Received 14th February 2011, Accepted 28th March 2011
DOI: 10.1039/c1cc10869g
The halogen-bonded adduct between DABCO and two molecules
of perfluorooctyl iodide (DABCOꢀ(C8F17I)2) acts as a recyclable
organocatalyst for the Morita–Baylis–Hillman reaction. This
‘‘supramolecular fluorous catalyst’’ is readily accessible and can
be recovered by simple precipitation/filtration.
Halogen bonding (X-bonding) is a class of non-covalent
interaction in which a halogen atom (I or Br) behaves as an
electron acceptor able to interact with an electron donor
species (a Lewis base or an anion).14,15 The electrophilic
character of these halogen atoms is very significant when they
are bonded to a strong electron-withdrawing group, such as a
fluorocarbon chain. During the last decade, X-bonding
has been successfully exploited in molecular self-organisation
processes: crystal engineering,16 liquid crystal materials,17
resolution of isomers,18 etc. Besides these applications, in
1998 Resnati suggested that the X-bonding donation ability
of perfluoroalkyl halides could be used as an alternative
to covalent perfluorinated ponytails to drag hydrocarbon
reactants from an organic phase.19,20 To our knowledge this
original idea did not find application whereas some X-bond
acceptor organocatalysts, such as quinuclidine and DABCO,
do exist.21 Indeed, 14N and 19F NMR experiments have shown
that these amines were able to form X-bonds with di- or
monoiodoperfluoroalkanes.15b,22
The current environmental requirements impose the minimum
of chemical waste during a synthesis process.1 In the field of
catalysis, this implies to recover the catalyst at the end of
the reaction and to reuse it for several cycles.2 While the
recyclability of organocatalysts generally rests on their immo-
bilization on solid supports,3 fluorous techniques constitute an
attractive alternative.4 Indeed, the introduction of perfluoro-
alkyl moieties into organic molecules deeply modifies their
physical properties and, as a consequence, they become
insoluble in water and most organic solvents. Thus, a molecule
tagged with fluorous ‘‘ponytails’’5 can be selectively separated
from other organic compounds through three methods:
(1) liquid–liquid extraction by partition between a fluorous
and an organic solvent,6 (2) solid phase extraction by means of
a fluorous reverse phase silica (FSPE)7 and (3) in some
advantageous cases by simple precipitation in conventional
solvents.8,9 While fluorous tag techniques have been widely
described in organometallic catalysis by using F-ligands
(e.g. phosphines bearing perfluoroalkyl chains),4,6a they have
been poorly applied to organocatalysts, and only a dozen of
examples have been addressed in the literature.10–12 All these
reports describe the multistep synthesis of the fluorous
catalysts in which the ponytails are covalently bonded to the
active molecule, and they can be recycled up to five times.10
In a recent communication, we disclosed an original
approach where a fluorous DMAP salt, C7F15CO2ꢁDMAPH+,
behaved as an effective recyclable catalyst for the acylation of
alcohols by anhydrides.13 We now report on a DABCO-based
fluorous organocatalyst 1 in which the fluorous tags are
‘‘grafted’’ in a supramolecular fashion through halogen-
bonding (Fig. 1).
From the above considerations, we reasoned that DABCO
could be associated with a perfluoroalkyl halide RfnX to form
a solid adduct 1, which would provide the following benefits:
(1) the X-bonded adduct 1 can be formed in a single step by
simply mixing two portions of RfnX with the diamine, (2) since
X-bonding is a supramolecular association, it is reversible,
thus allowing DABCO to be released as an active organo-
catalyst and (3) at the end of the catalytic reaction, the adduct
1 could be regenerated and, due to its fluorous character, it
could be precipitated and recovered. For this purpose, our
investigations started by mixing DABCO with various
perfluoroalkyl halides (2 equiv). Unfortunately with C4F9I,
C6F13I or C8F17Br no solid adduct was formed, whatever the
conditions used (solvent, concentration, temperature).
However, by adding a solution of C8F17I (mp 25 1C) in
dichloromethane to a solution of DABCO (mp 156 1C) in
the same solvent, the adduct DABCOꢀ(C8F17I)2 (1-Rf34
)
immediately precipitated as a solid (mp 93 1C), which was
Laboratoire BioCIS-CNRS, Faculte´ de Pharmacie, Univ Paris Sud,
´
ˆ
5 rue J.B. Clement, F-92296, Chatenay-Malabry, France.
E-mail: julien.legros@u-psud.fr; Fax: +33 1 46 83 57 40;
Tel: +33 1 46 83 57 44
w This publication is part of the web themed issue on fluorine chemistry.
z Electronic supplementary information (ESI) available: Experimental
details and analytical data. See DOI: 10.1039/c1cc10869g
Fig. 1 Fluorous organocatalyst 1.
c
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Chem. Commun., 2011, 47, 5855–5857 5855

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Table 1 Morita–Baylis–Hillman reaction between aldehydes and
Michael acceptors catalysed by 1-Rf34
The reaction scope was also extended to other Michael
acceptors. Methyl vinyl ketone was shown to be a good
partner (53–78%, entries 7–9), as well as acrylonitrile (66–92%,
entries 10–14), these two compounds reacting in the same
fashion as methyl acrylate. In contrast, 2-cyclohexen-1-one
was a poorer reactant and its reaction with 3-nitrobenzaldehyde
occurred in 60 h to afford the product 5a in 45% yield
(entry 15). It is worth noting that, if reaction times are
longer than those reported for the two other immobilized
quinuclidines described in the literature (ionic liquid-bond, grafting
on magnetic nanoparticles),25 this can be attributed to the lower
catalyst loading used in this work (10 mol% vs. 20–30 mol%).26
Then we assessed the recyclability of 1-Rf34 in a typical
reaction between 2,4-dichlorobenzaldehyde and methyl
acrylate on a 2.8 g scale (Table 2).y
a
Entry R1
R2
Time (h) Product 2–5 Yield (%)
1
2
3
4
5
6
7
8
2,4-Cl2C6H3 CO2Me
4-NO2C6H4 CO2Me
3-NO2C6H4 CO2Me
18
14
18
40
60
60
40
18
40
18
14
14
60
60
2a
2b
2c
2d
2e
2f
3a
3b
3c
4a
4b
4c
4d
4e
5a
90
91
92
80
80
0
60
78
53
88
66
92
91
71
45
4-ClC6H4
2-furyl
i-Pr
CO2Me
CO2Me
CO2Me
2,4-Cl2C6H3 COMe
4-NO2C6H4 COMe
9
4-ClC6H4
COMe
The larger scale used for this study did not affect the
reaction time, and full conversion into 2a occurred within
18 h (entry 1). At the end of the transformation, addition of
fluorophobic solvents, dichloromethane and acetonitrile to the
10
11
12
13
14
15
2,4-Cl2C6H3 CN
4-NO2C6H4 CN
3-NO2C6H4 CN
4-ClC6H4
Ph
CN
CN
b
reaction mixture induced the precipitation of pure 1-Rf34
,
3-NO2C6H4 C(O)(CH2)3 60
which was isolated by filtration (91% recovery). The filtrate
contained the Baylis–Hillman adduct 2a (90% yield) with no
traces of the catalyst, as confirmed by 1H and 19F NMR
analyses. The recovered organocatalyst was then reused for
2 further runs with no loss of activity (entries 2 and 3). The
catalyst still kept a significant activity up to five iterative
cycles, albeit with a little decrease (entries 4 and 5).
a
Reaction conditions: aldehyde (1 mmol), Michael acceptor (1.5 mmol),
b
MeOH (2 mmol), 1-Rf34 (0.1 mmol). 2-cyclohexen-1-one.
isolated in an excellent 94% yield after filtration. 19F NMR
comparison between the adduct 1-Rf34 and the pure iodoper-
fluorooctane showed a significant D|d(CF2I)| of 5.15 ppm, thus
confirming the halogen bonding nature of the association.23
To assess the promoting potency of 1-Rf34 in the Morita–
Baylis–Hillman reaction,24 we reacted this fluorous catalyst
(10 mol%) with aldehydes and Michael acceptors under the
attractive conditions previously described by Cheng: in the
presence of 2 equivalents of methanol.25b Results are reported
in Table 1.
In summary, we prepared a perfluorinated-tagged analogue
of DABCO through halogen bonding with perfluorooctyl
iodide, readily accessible in a single step. This supramolecular
fluorous organocatalyst efficiently promotes the Baylis–
Hillman reaction at a reasonable catalyst loading under simple
conditions, and it is easily recoverable by filtration. In
the future, this novel approach could be extended to other
catalysts, such as cinchona alkaloids, for enantioselective
transformations.
Under these conditions, 1-Rf34 efficiently promoted the
reaction between aromatic aldehydes and various partners in
14–60 h. Thus, methyl acrylate reacted with benzaldehyde
derivatives bearing electron-withdrawing groups (chloro- or
nitro-) in o-, m- as well as p-position within 14–40 h (80–92%,
entries 1–4). The reaction with furfural was more sluggish
(80% after 60 h, entry 5) while no reaction took place
with aliphatic aldehydes such as i-butyraldehyde (entry 6).
Notes and references
y Typical procedure for the Morita–Baylis–Hillman catalyzed by 1-Rf34
.
Synthesis of 2a: A 50 mL round-bottomed flask was charged with 2,4-
dichlorobenzaldehyde (16.3 mmol, 2.8 g), methanol (32.6 mmol, 1.04 g),
methyl acrylate (24.5 mmol, 2.11 g) and the adduct 1-Rf34 was added
(1.6 mmol, 2.0 g). The flask was then capped and the reaction mixture
was vigorously stirred at 20 1C. After 18 h, stirring was stopped and
dichloromethane (0.4 mL) was added, followed by dropwise addition
of acetonitrile until no more crystals appeared (ca. 8 mL). Then the
mixture was cooled to 0 1C and kept at this temperature for 2 h. The
supernatant containing the Baylis–Hillman product 2a was taken up
with a syringe, and transferred into a flask. The remaining solid was
washed with acetonitrile (5 mL), the supernatant was then taken up
and added to the previous liquid phase. Solid catalyst 1-Rf34 was
cleared from solvent traces under vacuum (1.82 g, 91%).27 The
combined liquid phases were evaporated under vacuum to afford 2a
as a yellow oil (3.1 g, 90%).28
Table 2 Assessment of 1-Rf34 as a recyclable catalyst in the reaction
between 1,3-dichlorobenzaldehyde and methyl acrylatea
Run Reaction time (h) Recovery of 1-Rf34 (%) Yield of 2a (%)
1 (a) Green Chemistry: Theory and Practice, ed. P. Anastas and
J. C. Warner, Oxford University Press, Oxford, 1998; (b) Green
Chemistry: Frontiers in Chemical Synthesis and Processes, ed. P. T.
Anastas and T. C. Williamson, Oxford University Press, Oxford, 1998.
2 I. Arends, R. Sheldon and U. Hanefeld, Green Chemistry and
Catalysis, Wiley-VCH, Weinheim, 2007.
3 For reviews on supported organocatalysts, see: (a) F. Cozzi, Adv.
Synth. Catal., 2006, 348, 1367; (b) M. Benaglia, A. Puglisi and
F. Cozzi, Chem. Rev., 2003, 103, 3401.
1
2
3
4
5
18
18
18
24
36
91
85
77
90
84
90
85
81
75
64
a
Reaction conditions: aldehyde (16.3 mmol), Michael acceptor
(24.5 mmol), MeOH (32.6 mmol), 1-Rf34 (1.6 mmol).
5856 Chem. Commun., 2011, 47, 5855–5857
c
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4 For reviews on fluorous chemistry, see: (a) W. Zhang, Green
Chem., 2009, 11, 911; (b) W. Zhang, Chem. Rev., 2009, 109, 749;
(c) W. Zhang, Chem. Rev., 2004, 104, 2531; (d) Handbook of
Fluorous Chemistry, ed. J. A. Gladysz, D. P. Curran and
2010, 46, 9025; (c) R. Cabot and C. A. Hunter, Chem. Commun.,
2009, 2005; (d) F. Zordan, L. Brammer and P. Sherwood, J. Am.
Chem. Soc., 2005, 127, 5979; for reviews, see: (e) G. Cavallo,
P. Metrangolo, T. Pilati, G. Resnati, M. Sansotera and
G. Terraneo, Chem. Soc. Rev., 2010, 39, 3772; (f) P. Metrangolo
and G. Resnati, Science, 2008, 321, 918; (g) P. Metrangolo,
F. Meyer, T. Pilati, G. Resnati and G. Terraneo, Angew. Chem.,
Int. Ed., 2008, 47, 6114; (h) Halogen Bonding: Fundamentals and
Applications, ed. P. Metrangolo and G. Resnati, Springer, Berlin,
2008.
I. T. Horva
5 J. A. Gladysz, Science, 1994, 266, 55.
6 For pioneer works, see: (a) I. T. Horva
´
th, Wiley-VCH, New York, 2004.
´
th and J. Rabai, Science,
´
1994, 266, 72; (b) A. Studer, S. Hadida, R. Ferritto, S.-Y. Kim,
P. Jeger, P. Wipf and D. P. Curran, Science, 1997, 275, 823.
7 For a review, see: W. Zhang and D. P. Curran, Tetrahedron, 2006,
62, 11837.
16 (a) D. Cincic, T. Friscic and W. Jones, Chem.–Eur. J., 2008, 14,
´ ´
8 (a) M. Wende, R. Meier and J. A. Gladysz, J. Am. Chem. Soc.,
2001, 123, 11490; (b) M. Wende and J. A. Gladysz, J. Am. Chem.
Soc., 2003, 125, 5861.
9 Teflon tape has also been used for fluorous catalysts delivery/
recovery: L. V. Dinh and J. A. Gladysz, Angew. Chem., Int. Ed.,
2005, 44, 4095.
747; (b) P. Metrangolo, F. Meyer, T. Pilati, D. M. Proserpio and
G. Resnati, Cryst. Growth Des., 2008, 8, 654; (c) T. Caronna,
R. Liantonio, T. A. Logothetis, P. Metrangolo, T. Pilati and
G. Resnati, J. Am. Chem. Soc., 2004, 126, 4500;
(d) P. Metrangolo and G. Resnati, Chem.–Eur. J., 2001, 7, 2511.
¨
17 (a) D. W. Bruce, P. Metrangolo, F. Meyer, T. Pilati, C. Prasang,
10 IBX: (a) T. Miura, K. Nakashima, N. Tada and A. Itoh,
Chem. Commun., 2011, 47, 1875TEMPO: (b) A. Gheorghe,
T. Chinnusamy, E. Cuevas-Yanez, P. Hilgers and O. Reiser, Org.
Lett., 2008, 10, 4171; (c) G. Pozzi, M. Cavazzini, O. Holczknecht,
S. Quici and I. Shepperson, Tetrahedron Lett., 2004, 49, 4245;
chiral sulfonamides: (d) T. Miura, K. Imai, M. Ina, N. Tada,
N. Imai and A. Itoh, Org. Lett., 2010, 12, 1620; (e) L. Zu, H. Xie,
H. Li, J. Wang and W. Wang, Org. Lett., 2008, 10, 1211; (f) L. Zu,
J. Wang, H. Li and W. Wang, Org. Lett., 2006, 8, 3077; chiral
thiourea: (g) L. Wang, C. Cai, D. P. Curran and W. Zhang,
Synlett, 2010, 433; 4-dialkylaminopyridine: (h) J. Legros,
B. Crousse and D. Bonnet-Delpon, J. Fluorine Chem., 2008, 129,
974; chiral imidazolidinone: (i) Q. Chu, W. Zhang and
D. P. Curran, Tetrahedron Lett., 2006, 47, 9287; cinchona
alkaloids: (j) F. Fache and O. Piva, Tetrahedron Lett., 2001, 42,
5655; (k) valine formamide: A. V. Malkov, M. Figlus, S. Stoncius
and P. Kocovsky, J. Org. Chem., 2007, 72, 1315; (l) prolinol:
H. Cui, Y. Li, C. Zheng, G. Zhao and S. Zhu, J. Fluorine Chem.,
2008, 129, 45.
G. Resnati, G. Terraneo, S. G. Wainwright and A. C. Whitwood,
Chem.–Eur. J., 2010, 16, 9511; (b) P. Metrangolo, C. Prasang,
G. Resnati, R. Liantonio, A. C. Whitwood and D. W. Bruce,
Chem. Commun., 2006, 3290; (c) J. W. Xu, X. M. Liu, J. K. P. Ng,
T. T. Lin and C. B. He, J. Mater. Chem., 2006, 16, 3540.
18 (a) P. Metrangolo, Y. Carcenac, M. Lahtinen, T. Pilati,
K. Rissanen, A. Vij and G. Resnati, Science, 2009, 323, 1461;
(b) A. Farina, S. V. Meille, M. T. Messina, P. Metrangolo,
G. Resnati and G. Vecchio, Angew. Chem., Int. Ed., 1999, 38, 2433.
19 V. Amico, S. V. Meille, E. Corradi, M. T. Messina and G. Resnati,
J. Am. Chem. Soc., 1998, 120, 8261.
20 It is worth noting that there is an example of organocatalysis
assisted by a perfluoroalkyl iodide: A. Bruckmann, M. A. Pena and
C. Bolm, Synlett, 2008, 900.
21 U. V. Mallavadhani and N. Fleury-Bregeot, in Encyclopedia of
Reagents for Organic Synthesis, ed. D. Crich, A. Charette,
P. L. Fuchs and G. Molander, Wiley, New York, 2010.
22 M. T. Messina, P. Metrangolo, W. Panzeri, E. Ragg and
G. Resnati, Tetrahedron Lett., 1998, 39, 9069.
11 Fluorous prolinols have also been used as precatalysts for CBS
reductions: (a) Q. Chu, Ma. S. Yu and D. P. Curran, Org. Lett.,
2008, 10, 749; (b) S. Goushi, K. Funabiki, M. Ohta, K. Hatano and
M. Matsui, Tetrahedron, 2007, 63, 4061; (c) Z. Dalicsek,
23 Performed at 20 1C in CDCl3 at a 0.5 mol Lꢁ1 concentration. See
supporting information for detailsz.
24 (a) V. Declerck, J. Martinez and F. Lamaty, Chem. Rev., 2009, 109,
1; (b) D. Basavaiah, A. J. Rao and T. Satyanarayana, Chem. Rev.,
2003, 103, 811; (c) D. Basavaiah, K. V. Rao and R. J. Reddy,
Chem. Soc. Rev., 2007, 36, 1581.
F. Pollreisz, A. Gomory and T. Soos, Org. Lett., 2005, 7, 3243.
´
¨
¨
12 For a remarkable effect of the fluorine atom in proline catalysis:
C. Sparr, W. B. Schweizer, H. M. Senn and R. Gilmour, Angew.
Chem., Int. Ed., 2009, 48, 3065.
13 D. Vuluga, J. Legros, B. Crousse and D. Bonnet-Delpon,
Chem.–Eur. J., 2010, 16, 1776.
14 (a) O. Hassel, Science, 1970, 170, 497; (b) H. A. Benesi and
J. H. Hildebrand, J. Am. Chem. Soc., 1949, 71, 2703.
15 (a) M. G. Sarwar, B. Dragisic, L. J. Salsberg, C. Gouliaras and
M. S. Taylor, J. Am. Chem. Soc., 2010, 132, 1646;
25 (a) S. Luo, X. Zheng, H. Xu, X. Mi, L. Zhang and J.-P. Cheng,
Adv. Synth. Catal., 2007, 349, 2431; (b) X. Mi, S. Luo and
J.-P. Cheng, J. Org. Chem., 2005, 70, 2338.
26 In a test experiment, catalyst 1-Rf34 was used at a 30 mol% loading
for the synthesis of 2a. After 7 h, 80% conversion was observed by
1H NMR.
27 It is important to evaporate solvents under moderate vacuum and
temperature since compound 1-Rf34 sublimates easily.
28 J. Cai, Z. Zhou, G. Zhao and C. Tang, Org. Lett., 2002, 4, 4723.
´
(b) E. Dimitrijevic, O. Kvak and M. S. Taylor, Chem. Commun.,
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 5855–5857 5857