Synthesis of pentafluorobenzene-based NHC adducts and their catalytic activity in the microwave-assisted reactions of aldehydes

Article abstract of DOI:10.1016/j.tetlet.2019.151419

N-Heterocyclic carbenes (NHCs) have been widely used in organometallic chemistry as ligands, as well as standalone organocatalysts in various reactions, mostly using aromatic aldehydes as substrates. We have previously demonstrated the efficiency of azolium-2-carboxylate zwitterions in the hydroxymethylation of aldehydes, especially aliphatic aldehydes, under microwave irradiation. In the present work, we report a series of pentafluorobenzene-based NHC adducts and their efficiency in the hydroxymethylation and self-condensation of aliphatic and aromatic aldehydes using microwave irradiation. The free carbenes are released under the reaction conditions and 1,3-dimesityl-2-(perfluorophenyl)imidazolidine and 1,3-bis(2,6-dimethylphenyl)-2-(perfluorophenyl)imidazolidine proved to be the most potent precatalysts.

Full text of DOI:10.1016/j.tetlet.2019.151419

Journal Pre-proofs
Synthesis of pentafluorobenzene-based NHC adducts and their catalytic activity
in the microwave-assisted reactions of aldehydes
Evanthia Papadaki, Victoria Magrioti
PII:
S0040-4039(19)31210-9
DOI:
https://doi.org/10.1016/j.tetlet.2019.151419
TETL 151419
Reference:
Tetrahedron Letters
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Accepted Date:
17 October 2019
13 November 2019
18 November 2019
Please cite this article as: Papadaki, E., Magrioti, V., Synthesis of pentafluorobenzene-based NHC adducts and their
catalytic activity in the microwave-assisted reactions of aldehydes, Tetrahedron Letters (2019), doi: https://doi.org/
10.1016/j.tetlet.2019.151419
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Synthesis of pentafluorobenzene-based NHC
adducts and their catalytic activity in the
microwave-assisted reactions of aldehydes
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Evanthia Papadaki, Victoria Magrioti*
Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15771, Greece
O
·
NHC C6HF5 (10 mol%)
·
O
(CH2O)n (3 equiv.), NHC C6HF5 (10 mol%)
O
R
R
OH
THF, MW, 100 °C, 1 h
R = alkyl or aryl
14 examples
R
H
R
THF, MW, 100 °C, 1 h
R = alkyl or aryl
4 examples
OH
10–79% yield
10–88% yield

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Synthesis of pentafluorobenzene-based NHC adducts and their catalytic activity in the
microwave-assisted reactions of aldehydes
Evanthia Papadaki, Victoria Magrioti
Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15771, Greece
———
ARTICLE INFO
ABSTRACT
 Corresponding author. Tel.: +30-210-727-4497; fax: +30-210-727-4761; e-mail: vmagriot@chem.uoa.gr
Article history:
Received
Received in revised form
Accepted
N-Heterocyclic carbenes (NHCs) have been widely used in organometallic chemistry as ligands,
as well as standalone organocatalysts in various reactions, mostly using aromatic aldehydes as
substrates. We have previously demonstrated the efficiency of azolium-2-carboxylate
zwitterions in the hydroxymethylation of aldehydes, especially aliphatic aldehydes, under
microwave irradiation. In the present work, we report a series of pentafluorobenzene-based NHC
adducts and their efficiency in the hydroxymethylation and self-condensation of aliphatic and
aromatic aldehydes using microwave irradiation. The free carbenes are released under the
reaction conditions and 1,3-dimesityl-2-(perfluorophenyl)imidazolidine and 1,3-bis(2,6-
dimethylphenyl)-2-(perfluorophenyl)imidazolidine proved to be the most potent precatalysts.
Available online
Keywords:
Green chemistry
N-Heterocyclic carbenes
Microwave irradiation
Organocatalysis
2009 Elsevier Ltd. All rights reserved.
conditions.20,21 These results prompted us to further investigate
the influence of other types of NHC precursors on this catalytic
1. Introduction
In organocatalysis small organic molecules predominantly
composed of C, H, O, N and other non-metal elements are used
to catalyze chemical reactions. Organocatalysts usually lack
sensitivity to moisture and oxygen, are often readily available at
low cost and present low toxicity when compared to
organometallic catalysts.1,2 Hence, organocatalyzed reactions are
an important alternative to metal-catalyzed processes.
system. Herein, we disclose the results of these endeavors.
2. Results and Discussion
In a recent report,21 we investigated the catalytic activity of
common imidazolylidene and imidazolinylidene NHCs. This
screening
allowed
us
to
identify
1,3-bis(2,6-
diisopropylphenyl)imidazol-2-ylidene (IDip·CO2) and 1,3-
dimesityl-imidazolin-2-ylidene (SIMes·CO2, 1) as promising
nucleophilic precursors for the synthesis of hydroxymethyl
ketones, via C–C bond formation, in high yields. The active
catalyst was formed in situ in the reaction mixture using
microwave irradiation, in the absence of a base (Scheme 1). This
method was successfully applied to aromatic, but most
importantly, to aliphatic aldehydes.
Research on N-heterocyclic carbenes (NHCs) has increased in
recent years and are recognized as highly useful and versatile
tools that can be applied in a wide range of organocatalytic
reactions due to their ability to react with aldehydes and generate
the corresponding reactive intermediates.3-7 The most common
NHC-catalyzed processes involve the reaction of an aldehyde
with the NHC catalyst to yield a Breslow intermediate.3 This
reactivity includes a polarity reversal of the substrate (umpolung
chemistry) to form a new C-C bond.6 This Breslow intermediate
is used in reactions such as benzoin condensations,3 Stetter
reactions8-10 and hydroacylations.11 NHC-catalyzed reactions can
also be used to form other reactive intermediates such as enolates
for aldol reactions and Michael additions,12,13 and homoenolates
for condensation reactions.14,15 NHCs can also be used to catalyze
a wide range of reactions where several types of NHCs may be
applied.16-18 However, the choice of a given type of NHC for a
particular reaction is often not clear.
(CH2O)n (3 equiv.)
O
NHC CO
O
2 (10 mol%)
OH
R
dry THF, MW, 100 oC, 1h
R
H
O
O
O
N
O
N
N
N
SIMes CO2 (1)
IDip CO2
Scheme 1. Microwave-assisted hydroxymethylation of heptanal (R =
n-hexyl) and benzaldehyde (R = phenyl) using NHC•CO2 as catalyst.
Some of these reactions, for instance the hydroxymethylation
of aldehydes, usually require heating for extended periods of time
(at least 24 h).19 We have recently showed that microwave
irradiation promoted the rapid and efficient conversion of
aldehydes and paraformaldehyde into α-hydroxymethyl ketones
using NHC organocatalysts under environmentally friendly
With these encouraging results in hand, we then decided to
focus our research on the synthesis of similar, yet more
accessible protected N-heterocyclic carbenes, capable of acting as
stand-alone catalysts for the hydroxymethylation of aldehydes. In

2
Tetrahedron Letters
this view, we wanted to study the effect of replacing the CO2
appropriate substituted aniline (Scheme 2). This reaction gave
high yields (70-99%) depending on the substrate. Diimines 4a-d
were synthesized according to literature procedures.24,25 For the
synthesis of diimine 4e, the aforementioned conditions26 were not
as effective; therefore, we modified the reaction conditions by
heating 1 equivalent of 2,3-butanedione and 2 equivalents of
aniline in methanol (instead of ethanol), in the presence of 98%
formic acid at 50 °C for 16 h. By using methanol, we succeeded
in the quantitative precipitation of 4e, since its solubility in
methanol is lower than ethanol.
protecting group by the C6HF5 group, thus overcoming the
difficulties of the previously reported cyclization procedures.22
According to the literature, the C6HF5 group can be satisfactorily
removed with heating to give the free carbene.23 The most widely
used approach for the synthesis of imidazolylidene and
imidazolinylidene NHC precursors is the introduction of the
precarbenic carbon in the cyclization step.
For the synthesis of the CO2-adducts,22 initial formation of the
corresponding salt is required. Then, the free carbene is released
using a base and finally the carbenic carbon is protected with the
CO2-group using carbon dioxide gas. On the contrary, in our
approach, the 2,3,4,5,6-pentafluorobenzaldehyde condenses with
the corresponding diamine to afford the desired protected
carbene, thus saving two extra steps and the selection of an
appropriate base. The C6HF5-based NHC adducts are air- and
moisture-stable solids, which represent convenient alternative
precursors of free carbenes.
The next step involved reduction of the diimines to the
corresponding diamines with excess NaBH4 at r.t. for 3 h. For
diamines 5a-d the reaction proceeded normally, however this
was not the case with diamine 5e. The use of excess NaBH4 or
LiBH4 at r.t. or at reflux did not produce diamine 5e in a
satisfactory yield. However, we were able to isolate the mixture
of the two isomers of diamine 5e in quantitative yield by using 2
equivalents of LiAlH4 in dry THF at 50 °C. The two pure
diastereoisomers were collected after separation by column
chromatography, in a cis:trans ratio of 1:2.
R
R
R
H
i
O
ii
Ar
N
Ar
N
Ar NH2
O
N
Ar
N
Ar
H
R
R
R
The final cyclization step for the synthesis of the NHC
precursors consisted of the condensation of 2,3,4,5,6-
pentafluorobenzaldehyde with the corresponding diamines in
glacial acetic acid. After a few hours, the catalysts precipitated as
white or light-yellow solids; they were then filtered off, rinsed
with cold methanol and dried under high vacuum. Precatalyst 6a
was fully characterized and the spectroscopic data were in full
agreement with the literature values,23 while precatalysts 6c and
6d are novel protected NHCs and their NMR spectra were
comparable to those of precatalyst 6a. The trans-catalyst 6e is
also a novel NHC precursor. During the final condensation step,
we also tried to obtain cis-6e under the same conditions, but it
did not precipitate. Different attempts at the synthesis of cis-6e
were made, but according to TLC monitoring of the reaction,
there was unsatisfactory conversion, presumably due to its higher
steric hindrance (for details, see the ESI). Despite our efforts,
only the trans isomer of 6e was isolated in a good yield.
2a-d
3a-b
4a-e
5a-e
iii
2
a
3
a
4 6
R
Ar
-
a
H
F
F
F
F
F
F
H
H
b
c
a
a
b
c
F
F
F
F
H
H
N
Ar
Ar
Ar
Ar
N
N
N
H3C
CH3
6a-d
6e
H
d
a
a
b
d
e
CH3
The synthetic protocol used for NHC adducts 6a and 6c-e, as
well as the reported literature procedure27 for precatalyst 6b, were
unsuccessful. Obviously, the large steric hindrance of the
isopropyl groups at the 2,6-positions of the phenyl ring blocks
the 2,3,4,5,6-pentafluorobenzaldehyde from effectively leading to
ring closure. For details on the various attempts for the synthesis
of 6b that failed, see the ESI. When a catalytic amount of 10-
camphorsulfonic acid was used as an acidic additive, precatalyst
6b successfully precipitated and was purified by recrystallization
from methanol/diethyl ether. These reaction conditions were also
applied in a final attempt to prepare cis-6e, however no solid
precipitated.
Scheme 2. General synthesis of NHC-adducts 6a-e. Reagents and conditions:
i) HCOOH (a few drops), o.n., (67-99%) for 4a-c: MeOH (0.6 M), r.t., for
4d: iPrOH/H2O 2:1 (0.6 M), r.t., for 4e: MeOH (0.6 M), 50 °C; ii) for 5a-d:
NaBH4 (8 equiv.), dry THF/abs. MeOH 6:4 (0.2 M), 0 °C to r.t., 3 h (87-
99%), for 5e: LiAlH4 (1 M in THF, 2 equiv.), dry THF (0.2 M), 0 °C to r.t., 3
h (99%); cis/trans : 1:2; iii) for 6a,c-e: 2,3,4,5,6-pentafluorobenzaldehyde (1
equiv.), glacial CH3COOH (0.1 M), r.t., o.n. (50-70%), for 6b: 2,3,4,5,6-
pentafluorobenzaldehyde (1 equiv.), 10-camphorsulfonic acid (0.1 equiv.),
dry CH2Cl2 (0.2 M), (80%).
Precatalyst SiMes·CO2 (1) was used as a reference for the
design of the NHCs. We initially decided to study the effect of
the C6HF5 group when compared to the CO2 group; therefore, we
synthesized precatalysts 6a and 6b for comparative purposes.
Furthermore, we synthesized the novel precatalysts 6c and 6d to
study the effect of the absence of p-CH3 and one o-CH3 group on
the catalytic activity. Finally, we increased the steric hindrance
on the distal carbons of the five-membered ring, while
maintaining the 2,4,6-trimethylphenyl group in NHC precursor
6e. During the experimental procedures, several difficulties arose
that will be discussed in detail.
Precatalysts 6a-e were then tested in the catalytic
hydroxymethylation of aldehydes. Heptanal and benzaldehyde
were chosen as representative aliphatic and aromatic aldehydes
and the experimental results are listed in Table 1. The reactions
were carried out using the microwave-assisted procedure
previously optimized in our laboratory.21 Thus, one equivalent of
an aldehyde was reacted with 3 equivalents of paraformaldehyde
in the presence of an NHC precursor (10 mol%) in dry
tetrahydrofuran for 1 h at 100 °C in a microwave reactor (50W
maximum power).
According to the synthetic procedure, the first step was the
condensation of glyoxal 3a or 2,3-butanedione 3b with the
Table 1. Microwave-assisted hydroxymethylation of heptanal and benzaldehyde using catalyst precursors 1 and 6a-e. Reagents and conditions: (CH2O)n (3
equiv.), NHC precursor (10 mol%), dry THF (3.3 M), MW at 50 W, 100 ºC, 1 h.

3
Yield (%)
Reactant
Product
1
6a
6b
6c
6d
trans-6e
77a
75 a
47 a
88 a
75 a
O
O
0%c
47 a, b
70 a, b
57 a, b
63 a, b
OH
H
O
O
44 a
15 a
18 a
11 a
<5%c
14 a
OH
Ph
Ph
H
aIsolated yield after flash column chromatography; bIsolated yield after flash column chromatography, performed using the NHC precursor (5 mol%); cConversion calculated by 1H NMR.
Table 2. Isolated (%) yield for the microwave-assisted hydroxymethylation
Precatalyst 6a gave high yields for the catalytic reaction and
appeared to be more effective for aliphatic aldehydes than the
corresponding CO2-adduct 1, while precatalyst 6b proved to be
of various aliphatic and aromatic aldehydes catalyzed by precursors 6a and
6ca.
less efficient. Precatalyst 6c gave 1-hydroxy-2-octanone 7c in a
(CH2O)n (3 equiv.)
O
O
NHC C6HF
5 (10 mol%)
similar yield compared to catalysts 1 and 6a, indicating that the
methyl group at the para-position of the aryl group on the
nitrogen atoms is not important. However, both methyl groups at
positions 2 and 6 are essential since precatalyst 6d bearing only
OH
R
dry THF, MW, 100 oC, 1h
R
H
7a-n
O
i
O
O
one methyl group at position
2
did not give the
OH
ii
OH
OH
hydroxymethylketone under these conditions. Finally, precatalyst
trans-6e gave similar yields as precatalyst 6a. Apparently, the
increase of the steric hindrance in the backbone of the five-
membered ring does not affect the efficiency of the catalyst.
i
ii
i
ii
7a
7d
7g
7b
7c
: 30% (35%)
: 40% (48%)
: 76% (88%)
O
O
O
Ph
OH
OH
OH
Ph
Following these results, precatalysts 6a and 6c seemed to be
the most promising. To extend our studies, we also tested them
using other aldehyde substrates. The yields of these conversions
are listed in Table 2. In the series from heptanal to butanal and
pentanal, precatalyst 6a produced the linear hydroxymethyl
ketones 7a and 7b in 30% and 40% yield, respectively, while
similar results were obtained using precatalyst 6c. The
progressive decrease in the yield when the alkyl chain was
shortened is probably due to the higher volatility of the reactants
and products, thereby leading to significant material loss during
the experimental setup and work-up. With bulkier aliphatic
substrates (7e, 7f, 7g), precatalyst 6a maintained its catalytic
activity, while 6c showed lower yields.
i
ii
i
i
7e
7f:
30%
: 74% (70%)
: 52%
O
(Boc)2N
O
(Boc)2N
O
O
O
OH
OH
OH
OH
ii
O
O
i
i
i
7h
7i
: 14% (<10)
: 21%
O
: 57 %
O
O
OH
ii
OH
O
O
O
i
ii
i
i
7j
7k
7l
: 15% (11%)
: <10% (<10%)
: 26 %
O
O
OH
OH
Finally, we investigated the reactivity of various para-
substituted benzaldehydes with paraformaldehyde in the presence
of 6a and 6c. We observed that both catalysts were less effective
using aromatic substrates and that the substituent of the para-
group of the benzaldehyde, either electron-donating or
withdrawing, did not affect the yield.
F
Cl
i
ii
i
7m
7n
: 23 %
: <10 % (<10 %)
a Isolated yield after flash column chromatography, using precursor 6a (i) and 6c (ii).
In the next series of experiments using precursor 6a with
heptanal and benzaldehyde, when the reaction time was increased
from 1 h to 2 and 3 h, the yield remained almost identical;
however, we observed the appearance of by-products.
In general, when comparing precatalysts 6a and 6c and 1, we
observed that 6a displays a significant difference in its efficiency
between aliphatic and aromatic substrates.
Looking closely at the mechanism of the catalytic conversion
(Scheme 3), one of the possible by-products is that of the
condensation reaction between two identical aldehydes (benzoin
condensation).28,29 Thus, we decided to explore the ability of
precatalysts 6a and 6c to catalyze the self-condensation reaction
of aldehydes (Table 3). We initially used benzaldehyde and
heptanal as representative aromatic and aliphatic substrates, and
then extended the study using p-anisaldehyde and methyl-4-
formyl benzoate. Precatalyst 6a converts benzaldehyde to 2-
hydroxy-1,2-diphenylethan-1-one 8a in 79% yield, while
heptanal gave 8-hydroxytetradecan-7-one 8b only in 42% yield.
For para-substituted benzaldehydes, the yield was substantially
reduced. A different reactivity was observed for precatalyst 6c,
which did not efficiently react with heptanal, but gave higher
yields for substituted aromatic aldehydes. The scope of this
reaction is currently under examination and will be reported in
due course.
Control experiments carried out at reflux in an oil bath at 70
ºC revealed that the NHC·C6HF5 precatalysts were almost
inactive at this temperature, as was precatalyst 1.21 Therefore, we
confirmed the vital importance of the microwave irradiation.
In order to study the release of the free carbenes from
precatalysts 6a and 6b, we prepared solutions of the precatalysts
in THF that were irradiated at 50 W maximum power and 100
°C, following our synthetic protocol. At 15 min, 30 min and 1
hour, a sample of the solution was taken, the solvent evaporated
and the release of the free carbene monitored by 19F NMR, as
indicated by the disappearance of the 19F peaks of the C6ΗF5
group. In both cases, the free carbenes were released after 15 to
30 minutes.

4
Tetrahedron Letters
O
Fellowship grant (GA. no.2286 / 14477). We would like to thank
O
Mes
N
H
R
Dr. E. Sakki and Dr. A. Paschalidou for the MS spectra.
R
H
N
N
Mes
Mes
Mes
N
References and notes
Mes
1.
Dalko, P. I.; Moisan, L. Angew. Chem. Int. Ed. 2004, 43, 5138-
5175.
O
OH
Mes
N
N
N
2.
3.
4.
MacMillan, D. W. C. Nature 2008, 455, 304-308.
Breslow, R. J. Am. Chem. Soc. 1958, 80, 3719-3726.
Marion, N.; Díez-González, S.; Nolan, S. P. Angew. Chem. Int.
Ed. 2007, 46, 2988-3000.
Mes
O
C
H
H
R
HO
R
N
Mes
O
R
H
5.
Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007, 107,
5606-5655.
O
O
OH
6.
7.
Bugaut, X.; Glorius, F. Chem. Soc. Rev. 2012, 41, 3511-3522.
Berkessel, A.; Yatham, V. R.; Elfert, S.; Neudörfl, J.-M.
Angew. Chem. Int. Ed. 2013, 11158-62.
Stetter, H. Angew. Chem. 1976, 88, 695-704.
Cookson, R. C.; Lane, R. M. J. Chem. Soc., Chem. Commun.
1976, 804-805.
R
R
R
OH
Scheme 3. Formation of α-hydroxymethylketone and self-condensation of an
8.
9.
aldehyde according to Breslow’s mechanism.
Table 3. Isolated (%) yield of microwave-assisted self-condensation of
aliphatic and aromatic aldehydes catalyzed by precatalysts 6a and 6ca.
10. Hachisu, Y.; Bode, J. W.; Suzuki, K. J. Am. Chem. Soc. 2003,
125, 8432-8433.
O
NHC C6HF
O
5 (10 mol%)
R
11. Chan, A.; Scheidt, K. A. J. Am. Chem. Soc. 2006, 128, 4558-
4559.
12. Nair, V.; Vellalath, S.; Poonoth, M.; Suresh, E. J. Am. Chem.
Soc. 2006, 128, 8736-8737.
R
dry THF, MW, 100 oC, 1h
R
H
OH
8 a-d
O
O
13. Chiang, P.-C.; Kaeobamrung, J.; Bode, J. W. J. Am. Chem.
Soc. 2007, 129, 3520-3521.
OH
OH
14. Burstein, C.; Tschan, S.; Xie, X.; Glorius, F. Synthesis 2006,
2006, 2418-2439.
i
ii
i
ii
8a
8b
: 79% (40%)
: 42% (<10%)
O
O
15. He, M.; Bode, J. W. Org. Lett. 2005, 7, 3131-3134.
16. Flanigan, D. M.; Romanov-Michailidis, F.; White, N. A.;
Rovis, T. Chem. Rev. 2015, 115, 9307-9387.
17. Mahatthananchai, J.; Bode, J. W. Acc. Chem. Res. 2014, 47,
696-707.
O
O
O
O
OH
OH
O
O
i
ii
i
ii
8c
8d
: 38% (60%)
: 30% (40%)
18. Menon, R. S.; Biju, A. T.; Nair, V. Beilstein J. Org. Chem.
2016, 12, 444-461.
19. Kuhl, N.; Glorius, F. Chem. Commun. 2011, 47, 573-575.
20. Nikolaou, A.; Kokotos, G.; Magrioti, V. Tetrahedron 2016, 72,
7628–7632.
21. Papadaki, E.; Delaude, L.; Magrioti, V. Tetrahedron 2017, 73,
7295-7300.
22. Van Ausdall, B. R.; Glass, J. L.; Wiggins, K. M.; Aarif, A. M.;
Louie, J. J. Org. Chem. 2009, 74, 7935-7942.
23. Nyce, G. W.; Csihony, S.; Waymouth, R. M.; Hedrick, J. L.
Chem. Eur. J. 2004, 10, 4073-4079.
24. Huang, J.; Nolan, S. P. J. Am. Chem. Soc. 1999, 121, 9889-
9890.
25. Delaude, L.; Szypa, M.; Demonceau, A.; Noels, A. F. Adv.
Synth. Catal. 2002, 344, 749-756.
26. Yuan, J.; Wang, X.; Mei, T.; Liu, Y.; Miao, C.; Xie, X.
Transition Met. Chem. 2011, 36, 433.
27. Bedford, R. B.; Betham, M.; Blake, M. E.; Frost, R. M.;
Horton, P. N.; Hursthouse, M. B.; Lopez-Nicolas, R. M. J.
Chem. Soc., Dalton Trans. 2005, 2774-9.
a Isolated yield after flash column chromatography, using precatalyst 6a (i) and 6c (ii).
3. Conclusion
In this work, catalyst precursors 6a-e were synthesized and
fully characterized. The introduction of the C6HF5-group was
effective for protection of the carbenic center and allowed the
release of the active carbene under conventional heating or
microwave irradiation. All NHC precursors were tested in the
hydroxymethylation of aldehydes using our previously reported
protocol, as well as in the benzoin condensation. It appears that
the presence of methyl groups at the 2 and 6-positions is essential
for their activity as organocatalysts. However, the introduction of
methyl groups on the carbon atoms of the five-membered ring
does not affect the yield of the reaction. This screening has
allowed us to identify precatalysts 6a and 6c as promising
nucleophilic catalysts for the synthesis of α-hydroxymethyl
ketones when aliphatic aldehydes are used via C–C bond
formation. In the benzoin condensation, precatalyst 6c showed
more promising results using aromatic aldehydes.
Acknowledgments
28. Stetter, H. Synthesis 1976, 1976, 733-735.
29. Hachisu, Y.; Bode, J. W.; Suzuki, K. Adv. Synth. Catal. 2004,
346, 1097-1100.
This research work was supported by the Special Account for
Research Grants of the National and Kapodistrian University of
Athens (SARG/NKUA) and E. P. by the Hellenic Foundation for
Research and Innovation (HFRI) and the General Secretariat for
Research and Technology (GSRT), under the HFRI PhD

5



Synthesis of pentafluorobenzene-based NHC
precursors
NHC-catalyzed synthesis of hydroxymethyl
ketones using MW irradiation
Efficient synthesis of aliphatic hydroxymethyl
ketones