Imidazol-2-ylidene-4-olate: An anionic N-heterocyclic carbene pre-programmed for further derivatization

Article abstract of DOI:10.1039/b907908d

The 4-hydroxyimidazolium salt, readily prepared in two steps by acylation of a formamidine and quaternization of the second nitrogen, affords, after deprotonation, the anionic imidazol-2-ylidene-4-olate, which can be complexed to a transition metal and st

Full text of DOI:10.1039/b907908d

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Imidazol-2-ylidene-4-olate: an anionic N-heterocyclic carbene
pre-programmed for further derivatizationw
´ ¨
Laure Benhamou, Vincent Cesar,* Heinz Gornitzka, Noel Lugan and Guy Lavigne*
Received (in Cambridge, UK) 21st April 2009, Accepted 11th June 2009
First published as an Advance Article on the web 25th June 2009
DOI: 10.1039/b907908d
The 4-hydroxyimidazolium salt, readily prepared in two steps by
acylation of a formamidine and quaternization of the second
nitrogen, affords, after deprotonation, the anionic imidazol-2-
ylidene-4-olate, which can be complexed to a transition metal
and still be subsequently functionalized at O or C backbone
atom in the outer coordination sphere of the metal.
Stable N-heterocyclic carbenes display a rich coordination
chemistry, with multiple applications in organometallic catalysis.1,2
Amongst their intrinsic interests is the possibility to modify their
steric and electronic ligand properties by playing with the nature of
the exocyclic nitrogen substituents. A more sophisticated way to
modulate those properties is to modify the heterocyclic backbone
connecting the two nitrogen atoms. To date, and for the most
currently investigated 5-membered NHCs based on imidazole and
imidazoline rings, this has been done by (i) incorporation of an
inorganic backbone (compound A),3 (ii) [4,5]-annelation to
delocalized systems (type B),4 or (iii) substitution at positions 4
and 5 of the imidazolylidene (type C).5 Such changes in the
architecture of the carbene have to be pre-programmed in the
early stages of the synthesis of the antecedent imidazolium
pre-ligand, but allow no further modulation after ring closure,
once the final structure is obtained. With these observations
in mind, we reasoned that incorporation of a reactive
functionality within the heterocycle might allow further
derivatization with better synthetic flexibility. The enolate
group, whose chemistry is extremely well known, appeared
as an ideal candidate in view of the synthesis of such a scaffold.
We were thus led to devise a simple synthetic route to
compound D, an anionic imidazol-2-ylidene-4-olate.6
Scheme 1 Synthesis of the 4-hydroxyimidazolium chloride 3.
Based on the keto-/enol-equilibrium of hydroxyaromatics,
the 4-hydroxyimidazolium salt 3, representing the appropriate
pre-ligand, was synthesized in high yield by acylation of the
formamidine 1 with chloroacetyl chloride, giving the intermediate
2, which was readily cyclized by quaternization of the second
nitrogen. The anticipated intermediate 4-oxoimidazolinium
salt 30 was not detected, due to its fast conversion into the
more stable 4-hydroxyimidazolium chloride 3. Clearly, here,
the aromaticity of the imidazolium ring appears as the driving
force favoring an equilibrium shift toward the enol form
(Scheme 1).
The formation of the imidazolium ring can be monitored by
IR spectroscopy, following the disappearance of the CQO
stretching band around 1700 cmꢀ1. The pre-ligand 3a was
crystallizedz and identified by X-ray diffraction analysis
(Fig. 1).
In the solution 1H NMR spectrum of 3, the protons in
positions 2 and 5 of the heterocycle appear as a characteristic
set of two doublets between 7 and 8 ppm, with a coupling
constant of 2.1 Hz. The chemical shift of the C1–H proton is
particularly shielded (d = 7.54 ppm for 3a, d = 7.56 (ꢁ0.03)
ppm for 3b) relative to a classical imidazolium chloride
(d 4 10 ppm),7 which may arise from a weaker hydrogen
bonding between this proton and the chloride anion which
is already involved in hydrogen bonding with the free
–OH group. This interaction also exists in the solid-state
structure of 3a (Fig. 1) where each chloride anion interacts
with two neighboring imidazolium units via a network of
hydrogen bonds O–Hꢂ ꢂ ꢂClꢂ ꢂ ꢂH–C.
CNRS, LCC (laboratoire de chimie de coordination),
205 route de Narbonne, F-31077 Toulouse Cedex 4, France and
´
Universite de Toulouse, UPS, INPT, 31077 Toulouse, France.
E-mail: vincent.cesar@lcc-toulouse.fr, guy.lavigne@lcc-toulouse.fr
w Electronic supplementary information (ESI) available: Experimental
details for the preparation of the reported compounds and crystallo-
graphic data (CIF files) for 3a, 4a and 7a. CCDC 728893–728895. See
DOI: 10.1039/b907908d
Two acidic protons are present in the cationic 4-hydroxy-
imidazolium salt 3 but they can be differentiated by their pKa
value and their reactivity. As expected, the most acidic
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Fig. 2 Molecular structure of 7a from single crystal X-ray structure
determination. Anisotropic displacement parameter ellipsoids are
shown at 50% and hydrogen atoms were omitted for clarity. Selected
bond lengths (A): Rh1–C1 2.020(3), C2–C3 1.500(4), C2–O1 1.217(3).
Fig. 1 Spatial arrangement of salt 3a in the solid-state structure obtained
by X-ray analysis. Anisotropic displacement parameter ellipsoids are
shown at 50%. Hydrogen atoms on mesityl units were omitted for clarity.
Selected bond lengths (A): C2–C3: 1.360(2), C2–O1A: 1.269(3).
and the tautomeric equilibrium shifted to the keto form. All
the characterizations were in agreement with this assumption,
both in solution, with a 1H NMR AB system for the two
diastereotopic C5 protons at d = 4.24 ppm,10 and in the solid
state with C4–C5 (1.500(4) A) and C4–O bonds (1.217(3) A)
lying, respectively, in the range of a typical single C–C bond
and double CQO bond (Fig. 2).11
At that stage of our investigation, we were interested in
determining whether further functionalization of the ligand
could be achieved after its complexation to a transition metal.
Starting from complex 7a, O-functionalization of the
coordinated NHC was carried out by deprotonation at low
temperature with one equivalent of LiN(SiMe3)2 followed by
the addition of a suitable electrophile (Scheme 3, upper
equation). With a silyl chloride (TBDMSCl) or a phosphorus(V)
chloride (Ph2P(QO)Cl), as incoming electrophiles, O-substitution
was observed, leading to the protected imidazol-2-ylidene-4-ol
complexes 8a and 9a. The main probe of the success of the
reaction was the disappearance of the AB system of the CH2
protons in 7a and the appearance of a singlet at d = 6.22 ppm
in 8a and at 6.18 ppm in 9a corresponding to the endocyclic
C5 proton.
function in 3 is the phenol-type –OH group. Indeed, it could be
readily deprotonated by reacting 3a with triethylamine to form
the mesoionic imidazolium-4-olate 4a.8 The anionic imidazol-
2-ylidene-4-olate 5a was generated quantitatively by treatment
of 3a with two equivalents of lithium bis(trimethylsilyl)amide
at 0 1C. In order to confirm its formulation as an NHC, 5a was
trapped with S8, and after neutralization of the enolate inter-
mediate using one equivalent of hydrogen chloride, compound
6a was isolated as a white, stable solid in 68% yield. Here,
since the heterocycle is no longer aromatic, the keto form is
solely obtained as judged by the appearance of a strong band
at n = 1747 cmꢀ1 in the IR spectra for the CQO bond and by
1
a singlet at d = 4.44 ppm in the H NMR integrating for 2H
corresponding to the two C5 protons (Scheme 2).
Reaction of the in situ generated carbene 5aꢂLi+ with half
an equivalent of [RhCl(1,5-COD)]2 produced after neutraliza-
tion the rhodium(I) complex 7a in good yield. As the imidazol-
2-ylidene was shown to possess less aromatic character than its
imidazolium precursor,9 the enol form should be less stabilized
Scheme 2 Mono- and bis-deprotonation of compound 3a with sub-
Scheme 3 Functionalization of complex 7a on the backbone of the
sequent trapping of the anionic NHC by sulfur or a rhodium precursor.
N-heterocyclic carbene.
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In a parallel experiment (Scheme 3, lower equation),
C-functionalization was successfully carried out using
paraformaldehyde as the electrophile according to an
aldolization–crotonization sequence. The olefinic QCH2
protons display a pair of doublets at d = 5.68 ppm and
4.87 ppm with a characteristic geminal coupling of 1.8 Hz.
In summary, we have developed a simple synthetic strategy
towards an anionic five-membered ring N-heterocyclic carbene
incorporating a reactive enolate group in its backbone. The
advantage of such a ligand is that it can be complexed with
transition metals, whereas its backbone can still be modified in
different ways after complexation. The concept disclosed here
will allow a divergent optimization and construction of
NHC-based catalysts in view to obtain better activities.12 By
extension, and upon suitable selection of the electrophile, it
should also be applicable to the generation of supported or
tagged catalysts directly from their soluble form. Studies
toward this goal are currently under investigation in our
laboratory.
3 K. E. Krahulic, G. D. Enright, M. Parvez and R. Roesler, J. Am.
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6 For other anionic NHCs, see: (a) V. Cesar, N. Lugan and
´
Support from the CNRS and from the ANR (programme
blanc ANR-08-BLAN-0137-01) is gratefully acknowledged.
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Notes and references
7 See
for
example:
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z Crystal data for 3a: C21H25ClN2O, M = 356.88, monoclinic,
a = 8.5416(3), b = 29.645(1), c = 8.7375(3) A, b = 118.109(2)1,
U = 1951.52(12) A3, T = 180(2) K, space group P21/c (no. 14), Z = 4,
32 567 reflections measured, 5587 unique (Rint = 0.0198) which were
used in all calculations. The final wR(F2) was 0.0680 (all data). Crystal
data for 7a: C29H36ClN2ORh, M = 566.96, triclinic, a = 12.5523(5),
b = 13.1214(4), c = 17.4887(7) A, a = 73.019(2)1, b = 89.920(1)1,
8 The molecular structure of compound 4a is depicted in the ESIw.
¨
9 For theoretical studies, see: (a) M. Tafipolsky, W. Sherer, K. Ofele,
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S. Gupta and M. K. Denk, Organometallics, 1999, 18, 1862;
3
ꢀ
g = 77.013(2)1, U = 2678.02(17) A , T = 176(2) K, space group P1
(c) C. Heinemann, T. Muller, Y. Apeloig and H. Schwarz,
¨
(no. 2), Z = 4, 17 559 reflections measured, 8754 unique (Rint = 0.0248)
which were used in all calculations. The final wR(F2) was 0.0432
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10 The mesityl groups are sterically hindered and block the rotation
around the Rh–CNHC bond (on the NMR time scale). Then
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diastereotopic.
11 F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G. Orpen
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¨
ꢃc
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