Switching the electron-donor properties of N-heterocyclic carbenes by a facile deprotonation strategy

Article abstract of DOI:10.1002/asia.200900410

Flip the switch! The facile and distinct variation of the electronic properties of an N-heterocyclic carbene (NHC) ligand is reported. In this process, a simple deprotonation/protonation strategy can render the NHC to be an electron-poor or an electron-ri

Full text of DOI:10.1002/asia.200900410

COMMUNICATION
DOI: 10.1002/asia.200900410
Switching the Electron-Donor Properties of N-Heterocyclic Carbenes by a
Facile Deprotonation Strategy
Akkattu T. Biju, Keiichi Hirano, Roland Frçhlich, and Frank Glorius*[a]
In the last few years, N-heterocyclic carbenes[1] (NHCs)
have found widespread and spectacular applications as orga-
nocatalysts[2] and as ligands in transition-metal catalysis.[3]
Arguably, the variation of the steric and electronic proper-
ties of NHCs will be of utmost importance for continued
success. However, whereas the steric demand of imidazoli-
um salt derived NHC ligands can be readily varied,[4,5] the
electronic variation of NHC ligands was found to be much
more challenging. Investigations by Organ,[6] Plenio,[7] and
Glorius[8] showed the influence of the substituents on the
imidazolium salt on the electronic properties to be rather
moderate (Figure 1). Recently, Roesler et al.[9] and Cꢀsar,
NHC ligand in different electronic states within one catalyt-
ic cycle. To the best of our knowledge, such a distinct and
reversible variation in electronic properties has not previ-
ously been described for any five-membered NHC ligand.
Inspired by a new synthetic method for the formation of
imidazolium salts from amidines and a-haloketones,[8a] our
study commenced with treating N,Nꢀ-diaryl formamidines 1
with commercially available 2-bromo methylesters 2 and di-
isopropylethylamine (NEtACTHNUTRGNE(UGN iPr)2) in propionitrile and stirring
the solution at 1208C (Scheme 1). The reaction of N,Nꢀ-di-
mesityl formamidine 1a and methyl 2-bromopropionate 2a
resulted in the formation of zwitterionic imidazolium salt 3a
as a pale yellow solid in 83% yield (Table 1). In addition,
several other differently substituted substrates were success-
fully coupled in this reaction. In our hands, this reaction was
found to be specific for the methyl a-bromo esters, since at-
tempted reactions with the ethyl ester derivative stopped
after the substitution step (intermediate I). Thus, the reac-
tion is expected to be initiated by the nucleophilic displace-
Figure 1. Three different sets of NHC ligands that have been electronical-
ly modified by variation of the X or R groups.
Lavigne et al.[10] reported on the first six-membered anionic
NHCs, with the negative charge being localized on the ring
framework.[11] Inspired by this work, herein we report the
facile switching of the electronic properties of an imidazoly-
lidene ligand by a simple deprotonation strategy. Not only
does this result in two electronically very distinct ligands,
but, in addition, this behavior is also reversible. Among
others, this creates the exciting possibility to employ an
Scheme 1. Formation of zwitterionic imidazolium salts.
Table 1. Formation of the zwitterionic imidazolium salts.[a]
Entry
R group
Ar group
3
t [h]
Yield[b] of 3 [%]
1
2
3
4
5
6
7
8
Me
Me
Et
Mes
A
3a
3b
3c
3d
3e
3 f
3g
3h
36
60
60
90
90
120
96
83
72
79
52
73
56
69
30
[a] Dr. A. T. Biju, K. Hirano, Dr. R. Frçhlich, Prof. Dr. F. Glorius
Westfꢁlische Wilhelms-Universitꢁt Mꢂnster
Organisch-Chemisches Institut
Et
N
nBu
nBu
Ph
R
Corrensstraße 40, 48149 Mꢂnster (Germany)
Fax : (+49)251-8333202
E-mail: glorius@uni-muenster.de
Ph
A
120
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.200900410.
[a] Reaction conditions: 1 (3 mmol), 2 (3 mmol), NEt
EtCN (6 mL), 1208C; [b] isolated yield.
ACHTUNGRTEN(NUNG iPr)2 (3 mmol),
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Chem. Asian J. 2009, 4, 1786 – 1789

1
ment of the bromide in 2 by the formamidine 1 leading to
intermediate I. I could then cyclize by quaternization of the
second nitrogen to form the oxoimidazolium salt II. Spectro-
scopic characterization of the zwitterionic salts 3 evidenced
the electron-richness of the ring: for example, in the
1H NMR spectrum of 3d (CDCl3), a characteristic high-field
shift of the C2-H proton of the imidazolium ring was ob-
served, namely d 6.90 ppm as compared to 9–10 ppm typi-
cally obtained for most imidazolium salts. Finally, the struc-
ture of zwitterions 3 was unequivocally established by
single-crystal X-ray analysis of 3d (Figure 2).[12]
sponding to the N2CH proton at d 7.64 in the H NMR spec-
trum of 3g in [D8]THF) as well as the appearance of a
highly deshielded 13C NMR signal at d 201.9 ppm showed
the formation of free NHC in solution.[13] The formation of
the anionic carbene 4g was confirmed by the subsequent
trapping of the generated NHC with elemental sulfur fol-
lowed by quenching the reaction mixture with saturated
aqueous NH4Cl to furnish the 2-thioxo-imidazolidin-4-one
derivative 6g in 79% yield (Scheme 2).[14] Again, the struc-
ture of 6g was unequivocally confirmed by single crystal X-
ray analysis (Figure 3).[12]
Figure 3. Crystal structure of the thiourea 6g in ball and stick representa-
tion.
Figure 2. Crystal structure of the zwitterionic imidazolium salt 3d in ball
À
and stick representation. Selected bond lengths [ꢄ] and angles [8]: N1
À
À
À
À
C2 1.338(3), C2 N3 1.345(3), N3 C4 1.424(3), C4 C5 1.387(3), C5 N1
A reliable and widely accepted method for the determina-
tion of electronic properties is the IR spectroscopic analysis
of the CO stretching frequencies of (L)Ni(CO)3,
(L)Rh(CO)2Cl, (L)Ir(CO)2Cl, or related complexes.[15] In
the context of the enormous reference data available for the
(L)Ir(CO)2Cl[16] and based on our experience with the Ir
complexes,[5,8,17] we decided to synthesize the corresponding
Ir complexes of the zwitterionic imidazolium salts. The reac-
À
À
À
À
1.398(3), N1 C11 1.451(3), N3 C31 1.434 (3), C4 O1 1.253(3), C5 C6
1.468(3); C5-N1-C2 110.5(2), C11-N1-C2 123.4(2), C5-N1-C11 125.0(2),
N1-C2-N3 107.0(2), C2-N3-C4 110.9(2), C2-N3-C31 124.6(2), C4-N3-C31
124.4(2), N3-C4-C5 104.4(2), N3-C4-O1 122.3(2), O1-C4-C5 133.3(2), C4-
C5-N1 107.3(2), C4-C5-C6 128.4(2), N1-C5-C6 124.3(2); C12-C11-N1-C2
89.0(3), C32-C31-N3-C2 83.3(3).
With these novel zwitterionic imidazolium salts[10b] in
hand, the formation of the corresponding carbenes and their
properties were investigated. The five-membered anionic
carbene 4g was generated quantitatively by treatment of 3g
tion of 3 with [Ir
lowed by immediate treatment of the resultant (NHC)Ir-
AHCTUNGTREN(GNUN COD)Cl with CO, afforded the (NHC)Ir(CO)2Cl com-
ACHTUNGTNER(NUNG COD)Cl]2 in the presence of LiHMDS, fol-
with
lithium
bis(trimethylsilyl)amide
(LiHMDS)
plexes 7 in good yield. In the Ir complex, the reactive eno-
late group in the backbone of compounds 3 changed to the
stable keto form of neutral NHC ligand 5 (Scheme 3).
The Ir carbonyl complex was
(Scheme 2). The disappearance of the most deshielded sin-
glet in the H NMR spectrum (in [D8]THF) of 4g (corre-
1
characterized by spectroscopic
techniques. For example, in the
IR spectrum of 7g measured in
CH2Cl2, the CO stretching was
observed
at
2075.8
and
1989.5 cmÀ1 corresponding to
the absorption at d 179.6 and d
168.2 ppm in the 13C NMR
1
spectrum. In the H NMR spec-
trum of 7g, the benzylic C-H
proton was discernible at
5.47 ppm.
d
Scheme 2. Investigation of the NHC formation.
Chem. Asian J. 2009, 4, 1786 – 1789
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F. Glorius et al.
COMMUNICATION
Scheme 3. Formation of NHCIr(CO)2Cl complex.
For getting insight into the electronic properties of the
generated NHCs and to compare this new class of ligands
with known NHCs, the CO stretching can be converted to
the corresponding Tolman’s Electronic Parameter (TEP)
using the improved linear regression-based method by
Nolan et al.[16] The TEP value for 5g in complex 7g is
2057.7 cmÀ1, which revealed that the NHC ligand in 7g is
significantly less electron-rich than IMes or SIMes. Thus, the
equilibrium between keto (5g) and enol form (5g’) of the
NHC ligand in 7g is strongly shifted to the side of the keto
form 5g. Next, the anionic Ir complex 8g was smoothly gen-
erated by treating 7g with LiHMDS (Scheme 4).
Figure 4. A section from the IR spectra for reactions using 7g and differ-
ent amounts of base.
In conclusion, we have un-
covered a facile and straightfor-
ward method for the one step
synthesis of zwitterionic imida-
zolium salts and the five-mem-
bered anionic carbenes derived
thereof.[10b]
study reveals the electronic
nature of the corresponding
Moreover,
this
Scheme 4. Switching the electronic nature of the NHC ligand by deprotonation.
NHC ligands, for the first time
In the IR spectrum of 8g measured in CH2Cl2, the CO
stretching has been observed at 2058.4 and 1973.9 cmÀ1 cor-
responding to a TEP value of 2043.7 cmÀ1. This shows that
the anionic carbene 4g in 8g is much more electron-rich
than IMes or even IAd (TEP=2049.5 cmÀ1). The conversion
of complex 7g to 8g by deprotonation of the NHC ligand
upon addition of LiHMDS has been visualized by an IR ti-
tration experiment (Figure 4). Treatment of 7g with differ-
ent equivalents of LiHMDS resulted in a clean shift of the
stretching frequency of the CO ligands (nCO) from 2076 cmÀ1
to 2058 cmÀ1 and from 1989 cmÀ1 to 1974 cmÀ1.[13] This analy-
sis of the (nCO) of the Ir(CO)2NHC complex allows a quanti-
tative assessment of the carbenes electronic properties. The
obtained shift is in agreement with the conversion of the
electron-withdrawing keto form of 7g (much less electron-
rich than IMes) to the electron-donating enolate form of the
NHC ligand in 8g (much more electron-rich than IMes)
(Table 2). Additionally, this is confirmed by a greatly re-
duced intensity of the lactam carbonyl peak at 1767 cmÀ1.
To the best of our knowledge, this dramatic shift in electron-
ic properties by deprotonation of an NHC ligand has not
been previously analyzed or reported. Moreover, this pro-
cess can be reversed by the addition of acid (e.g., HOTf) to
a solution of deprotonated complex 8g resulting in the for-
mation of complex 7g.[13] This reversibility adds significantly
to the potential of this new class of NHC ligands.
demonstrating the ready switching of electron-donor proper-
ties by a simple and reversible deprotonation/protonation
strategy. The investigation of applications of these carbenes
in challenging organocatalyzed and transition-metal cata-
lyzed reactions is ongoing in our laboratories.
Table 2. Comparison of nCO of IrNHC(CO)2Cl complexes.[a,b]
Entry
Ligand
nCO [cmÀ1
]
nCOav [cmÀ1
]
Calculated
TEP[b] [cmÀ1
]
1
2
3
4
5
6
5g in 7g
5e in 7e
SIMes
IMes
IAd
4g in 8g
2075.8, 1989.5
2075.1, 1989.0
2068.0, 1981.2[16]
2066.4, 1979.8[16]
2063.4, 1979.8[16]
2058.4, 1973.9
2032.7
2032.1
2024.6
2023.1
2021.6
2016.2
2057.7
2057.2
2050.8
2049.6
2048.3
2043.7
[a] NHCs given in order of descending TEP value (increasing electron-
av
richness); [b] values calculated by: TEP (cmÀ1)=0.847x+336 [x=nCO
(cmÀ1)].[16]
Acknowledgements
Generous financial support by the Fonds der Chemischen Industrie, the
Alexander von Humboldt Foundation (fellowship for A.T.B.), and the
Deutscher Akademischer Austauschdienst (fellowship for K.H.) are
gratefully acknowledged. Skillful assistance by Dr. Klaus Bergander
(NMR), Dr. Heinrich Luftmann (MS), and Dr. Kiril Axenov is gratefully
acknowledged. The research of F.G. is supported by the Alfried Krupp
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ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2009, 4, 1786 – 1789

Switching the Electron-Donor Properties of N-Heterocyclic Carbenes
Prize for Young University Teachers of the Alfried Krupp von Bohlen
and Halbach Foundation.
V. Cꢀsar, H. Gornitzka, N. Lugan, G. Lavigne, Chem. Commun.
2009, 4720.
[11] For the tethering of NHC ligands with negatively charged entities,
anionic tethered NHCs, see the following review: S. T. Liddle, I. S.
Edworthy, P. L. Arnold, Chem. Soc. Rev. 2007, 36, 1732.
[12] X-ray crystal structure analysis of 3d: formula C29H40N2O, M=
432.63, colorless crystal 0.35ꢇ0.15ꢇ0.15 mm, a=12.4371(4), b=
Keywords: carbenes · electronic properties · enolates ·
heterocycles · ligand design
22.8654(6), c=20.1798(6) ꢄ, b=103.716(1)8, V=5575.1(3) ꢄ3, 1calc
1.031 gcmÀ3 m=0.471 mmÀ1
empirical absorption correction
=
,
,
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428.57, colorless crystal 0.30ꢇ0.25ꢇ0.10 mm, a=8.5414(1), b=
10.8381(2), c=14.3477(2 ꢄ, a=88.883(1), b=75.835(1), g=
81.749(1)8, V=1274.32(3) ꢄ3, 1calc =1.117 gcmÀ3
, ,
m=1.266 mmÀ1
empirical absorption correction (0.703ꢀTꢀ0.884), Z=2, triclinic,
¯
space group P1 (No. 2), l=1.54178 ꢄ, T=223(2) K, w and f scans,
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Received: July 27, 2009
Published online: September 29, 2009
Chem. Asian J. 2009, 4, 1786 – 1789
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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