Acyl protection strategy for synthesis of a protic NHC complex via N-acyl methanolysis

Article abstract of DOI:10.1021/om100452g

In a new strategy for the synthesis of protic NHC complexes, iridium and rhodium complexes of N-benzoyl-substituted NHCs are first generated by direct deprotonation of an acyl-protected imidazolium salt. Deprotection of the acyl group with methanol then g

Full text of DOI:10.1021/om100452g

5728 Organometallics 2010, 29, 5728–5731
DOI: 10.1021/om100452g
Acyl Protection Strategy for Synthesis of a Protic NHC Complex via
N-Acyl Methanolysis†
Graham E. Dobereiner, Catherine A. Chamberlin, Nathan D. Schley, and
Robert H. Crabtree*
Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520
Received May 10, 2010
Summary: In a new strategy for the synthesis of protic NHC
requires basic conditions, which is incompatible with the
acidic N-proton of a protonated salt. As a result, the methods
that are known for the synthesis of protic NHC complexes are
indirect and specific to particular ligand scaffolds or metal
precursors. We thought that the removal of a protecting
group at nitrogen would, after metalation, afford a more
general route to protic NHC metal complexes. C-N bond
cleavage to form protic NHC ligands has been reported with
heterogeneous conditions (silica gel)2c and via a carbene-
mediated process;2b however the mechanisms of these reac-
tions are not yet well understood, and their generality is not
yet determined. There is also precedent for a Si-N bond
cleavage to form a protic NHC complex.2f
Our efforts focused on the use of a benzoyl-substituted
imidazolium salt as an NHC precursor. Acyl imidazolium
salts are potent electrophiles and can be utilized as stoichio-
metric acylating agents.4 Though they formally contain amide
bonds, these species do not show the deactivating resonance of
normal amides due to the contribution of the imidazole ring.
Thus, these salts react rapidly and irreversibly with a wide
range of mild nucleophiles, including water and methanol,
generating N-protonated imidazolium salts.
complexes, iridium and rhodium complexes of N-benzoyl-
substituted NHCs are first generated by direct deprotonation
of an acyl-protected imidazolium salt. Deprotection of the acyl
group with methanol then gives methyl benzoate and the protic
NHC. This sequence represents a new strategy for the synth-
esis of protic NHC complexes. We expect this strategy to have
useful generality.
Introduction
N-Heterocyclic carbene (NHC) ligands show a wide range
of electronic and steric variability that makes them well-
suited for applications such as homogeneous catalysis.1
Despite the wide variety of N-substitutions in the imidazole-
derived ligand scaffold that has been investigated, a limited
number of examples of the parent N-H substitution have
been reported.2 This is chiefly because the free protic NHC
rapidly tautomerizes to the stable azole, and thus indirect
methods are needed for the synthesis of protic NHC com-
plexes. Protic NHC ligands tend to be “noninnocent” in
certain cases, undergoing C-N tautomerization,2b,c or a 1,3
ligand-to-metal hydrogen shift,3 or a deprotonation to form
an anionic aryl ligand.2d In other cases they can be stable,
in which case the N-H group may confer advantages in
homogeneous catalysts. Ruiz et al.2g have recently reported
two new methods for the generation of protic NHC ligands
assisted by coordination of the precursor species to manga-
nese(I). One of them implicates the coupling of isocyanides
with propargylamines, and the other is based on tautomeri-
zation of N-coordinated imidazoles.
We outline a synthetic strategy that allows for the synthesis
of monodentate protic NHC complexes (Scheme 1). The
approach utilizes N-acyl imidazolium salts as NHC ligand
precursors, allowing for straightforward metalation of the
ligand and C-N bond cleavage upon exposure to nucleo-
philic solvent to form the protic species.
Results
Ligand Synthesis and Metalation. Acyl imidazolium salts
can be generated by reaction of an acyl imidazole with a
strong alkylating agent5 or alternatively by addition of an
acid chloride to an N-substituted imidazole.6 We found that
the salt 2can be isolated in good yield from reaction of imidazole
1 and trimethyloxonium tetrafluoroborate (Meerwein’s salt)
(Scheme 2). Salt 2 was chosen for this study principally because
it could be easily isolated and crystallized as a white solid. The
dicarboxylic ester functionality was originally selected in
connection with other work, not reported here, in which
attachment of the catalyst to a metal oxide surface was
intended. Though 2 is moisture sensitive, it can be stored in
anhydrous conditions for short periods. Single crystals of
2 were grown and subjected to X-ray crystallographic analysis
(Figure 1). The benzoyl substitution is oriented away from
A systematic study of these intriguing ligands has been
hampered by the paucity of methods available for their syn-
thesis. Traditional metalation of imidazolium salts typically
† Part of the Dietmar Seyferth Festschrift. Dedicated to Dietmar Seyferth
for his outstanding contributions to the field.
*To whom correspondence should be addressed. E-mail: robert.
crabtree@yale.edu.
(1) Crabtree, R. H. J. Organomet. Chem. 2005, 690, 5451. Díez-
ꢀ
Gonzalez, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109, 3612.
(2) Representative examples: (a) Lewis, J. C.; Wiedemann, S. H.;
Bergman, R. G.; Ellman, J. A. Org. Lett. 2003, 6, 35. (b) Burling, S.;
Mahon, M. F.; Powell, R. E.; Whittlesey, M. K.; Williams, J. M. J. J. Am.
Chem. Soc. 2006, 128, 13702. (c) Wang, X.; Chen, H.; Li, X. Organome-
tallics 2007, 26, 4684. (d) Miranda-Soto, V.; Grotjahn, D. B.; DiPasquale,
A. G.; Rheingold, A. L. J. Am. Chem. Soc. 2008, 130, 13200. (e) Araki, K.;
Kuwata, S.; Ikariya, T. Organometallics 2008, 27, 2176. (f) Brendler, E.;
Hill, A. F.; Wagler, J. Chem.;Eur. J. 2008, 14, 11300. (g) Ruiz, J.; Berros,
A.; Perandones, B. F.; Vivanco, M. Dalton Trans. 2009, 6999.
(4) Watkins, B. E.; Rapoport, H. J. Org. Chem. 1982, 47, 4471.
(5) Smith, J. J. Am. Chem. Soc. 1976, 98, 3598.
(3) Song, G.; Su, Y.; Periana, R. A.; Crabtree, R. H.; Han, K.; Zhang,
H.; Li, X. Angew. Chem., Int. Ed. 2010, 49, 912.
(6) Wolfenden, R.; Jencks, W. P. J. Am. Chem. Soc. 1961, 83, 4390.
r
pubs.acs.org/Organometallics
Published on Web 06/29/2010
2010 American Chemical Society

Note
Organometallics, Vol. 29, No. 21, 2010 5729
the benzimidazole ring, with the carbonyl oxygen in close
˚
proximity (2.561 A) to an aromatic benzimidazole hydrogen.
synthesized the NHC-Ir(CO)2Cl species 5 by treating com-
plex 3 with 1 atm of carbon monoxide for several minutes in
dichloromethane (Scheme 4). The carbonyl stretching fre-
quencies (ν(CO)) found in the infrared spectra of complexes
of this type are a measure of electron donor power that
closely correlates with the Tolman LNi(CO)3 scale.9 The
average stretching frequency of the symmetric and asym-
metric carbonyl peaks for 5 is 2025.7 cm-1. For comparison,
the 1,3-dimesitylimidazolidin-2-ylidene (SIMes) carbene lig-
and has a ν(CO)av of 2024.6 cm-1 on the NHC-Ir(CO)2Cl
scale.9c
Since this seems contrary to the steric preference of the
system, a dipole-dipole interaction between the CdO and
CdN bonds may be responsible for the conformations.
Because benzoyl imidazolium salts react rapidly with nucleo-
philes, only the non-nucleophilic base lithium bis(trimethyl-
silyl)amide (LiHMDS) was suitable for metalation. 2 reacts
with commercially available [Ir(cod)Cl]2 in the presence of
LiHMDS to provide the neutral iridium species 3. The analo-
gous rhodium compound 4 can be generated using [Rh(cod)-
Cl]2 and LiHMDS under similar reaction conditions (Scheme 3).
These seem to be the only reported iridium or rhodium com-
plexes that contain an NHC with N-acyl substitution. There is
precedent for generation of a gold(I) N-benzoyl NHC com-
plex by treatment of a trimeric Au-imidazole species with
benzoyl chloride.7 Additionally palladium(II) N-carbamoyl
NHCs have been reported.8
The reactions of Scheme 3 are performed in dichloro-
methane, in which the benzimidazolium salt is only sparingly
soluble. Upon addition of a hexane solution of LiHMDS to
the reaction suspension, a vivid color change occurs at once:
the iridium reaction darkened from yellow to dark brown,
while the rhodium reaction changed from yellow to green
upon base addition. In both cases the suspension becomes a
yellow-orange homogeneous solution as the salt is metalated.
This color change occurs in the absence of the imidazolium
salt and thus may arise from adduct formation between the
base and the metal precursor. The adduct then slowly reacts
with the azolium salt to form the NHC complex. However,
we could not isolate or characterize this adduct, so its nature
remains unknown.
Figure 1. ORTEP diagram of 2 with 30% probability ellipsoids.
Properties of Benzoyl NHC Complexes. The resulting
complexes 3 and 4 are air stable both in the solid state and
in solutions of non-nucleophilic solvents. X-ray crystallo-
graphic analysis of 3 shows that the benzoyl wingtip has a
very similar orientation to that seen in the free benzimidazol-
ium salt (Figure 2). Comparing the free salt with the co-
ordinated NHC (Table 1) shows that the bond distances of
the salt are only slightly modified by metalation; the lengths
of the C-N and C-O bonds of the benzoyl substitution do
˚
not change more than 0.01 A. On the basis of bond lengths,
the coordinated N-benzoyl NHC appears to maintain the
weak amide resonance seen in the free salt, contributing to
the strong electrophilicity of the acyl in this species.
To estimate the relative electron donor character of the
benzoyl-substituted NHC versus other NHC ligands, we
Figure 2. ORTEP diagram of 3 with 30% probability ellipsoids.
˚
Selected bond lengths (A): Ir(1)-C(1) 1.999, Ir(1)-Cl(1) 2.368,
N(1)-C(3) 1.439, N(1)-C(1) 1.373, N(2)-C(1) 1.347, N(2)-C
(2) 1.435, C(3)-O(1) 1.212.
Scheme 3. Metalation of an N-Benzoyl Benzimidazolium Salt
Scheme 1. Strategy for the Synthesis of Protic NHC Complexes
Scheme 2. Synthesis of the Benzimidazolium NHC Ligand Precursor

5730 Organometallics, Vol. 29, No. 21, 2010
Dobereiner et al.
Table 1. Comparison of Bond Lengths in the Free Salt versus the
Coordinated NHC Species
(CDCl3), a value consistent with reports of other imidazolyl-
based protic NHCs.2c,d When the bond cleavage is performed in
deuterated methanol, the resulting material is identical by
1H NMR except for a reduction in intensity of the N-H signal.
A broad band in the infrared spectra for this species at 3380 cm-1
is consistent with literature values for an N-H stretch.3
The crystal structure of 7 confirms the loss of the benzoyl
substitution on the carbene ligand (Figure 3). The N-H
proton was located in the difference density map and
refined isotropically without geometric restraint. Its pre-
sence may additionally be inferred from the charge balance
of the overall structure together with the NMR and IR data.
˚
length in salt (A)
˚
length in complex (A)
bond
The PF6 anion is moderately disordered. The closest
˚
a
b
c
d
e
1.470(4)
1.313(5)
1.345(4)
1.448(5)
1.205(5)
1.434(9)
1.346(9)
1.372(9)
1.438(9)
1.211(8)
N-H F-P distances of 2.285 and 2.365 A are consistent
3 3 3
with a weak interaction. The metal-carbon bond length
(2.004 A) is consistent with ligand carbene character and
largely unchanged from the bond length of the parent neutral
˚
˚
complex 3 (1.999 A).
Scheme 4. Formation of a Benzoyl NHC Bis-carbonyl Complex
Discussion
Li and co-workers find phenanthroline-based protic NHC
complexes of iridium(I) can give a 1,3 hydrogen shift from
N to Ir to give an aryl metal hydride.3 Such a shift is not
apparent for this cationic species; no iridium hydride signals
were detected in the proton NMR spectra in CDCl3 or CD2Cl2.
The mechanism of the C-N bond cleavage may be analo-
gous to the hydrolysis of acyl imidazolium salts. Studies on
acid-catalyzed N-acyl imidazole hydrolysis suggest that
metal ions are capable of enhancing the reaction rate;10 no
data on metal-mediated acyl imidazolium bond cleavage
could be found in the literature. We have no evidence that
metalation affects the electrophilicity of the acyl imidazo-
lium cation. Transient carbonyl coordination to the metal
center is conceivable; the d8 square-planar geometry predo-
minates, but five-coordinate 18-electron iridium(I) species
are also known.3 However, attempts to form an NHC-O
chelate by addition of silver salts of noncoordinating anions
to complex 3 resulted in decomposition. The bond lengths of
the amide C-N and C-O bonds are largely unchanged once
metalation has occurred, suggesting that the benzoyl group
remains a good electrophile despite deprotonation and co-
ordination. We therefore believe this type of bond cleavage
may be a useful general route.
Generation of a Protic NHC Species. An insoluble air-
sensitive purple solid precipitated from a methanolic suspension
of complex 3 over several days under inert atmosphere. The
1H and 13C NMR of this material indicate a bound 1,5-
cyclooctadiene, and a downfield 13C chemical shift (192.09 ppm,
CDCl3) is assigned to an iridium(I) NHC species (see Sup-
porting Information). The benzimidazole ring resonances
are present, but not those of the benzoyl protecting group.
The resulting solution contains methyl benzoate, consistent
with the expected C-N bond cleavage. We propose this
material is the neutral protic NHC complex, despite the abs-
ence of an N-H proton signal in the NMR spectra, which
could be diminished in intensity due to broadening and H-D
exchange. This material has thus far resisted rigorous puri-
fication or X-ray crystallographic analysis, so we looked for
possible derivation that would be tractable.
Iridium(I) complex 3 can be treated with a phosphine and a
noncoordinating anion to form a cationic species. Addition of
tricyclohexylphosphine to complex 3 was unsuccessful, how-
ever, presumably due to the steric constraints. Triphenylpho-
sphine can be employed in the presence of KPF6 to generate 6,
which is stable in air and in solution for extended periods.
Dissolution of N-acyl species 6 in methanol immediately
affords an equivalent of methyl benzoate and protic N-
heterocyclic carbene complex 7 (Scheme 5). Unlike the
cationic benzoyl NHC complex, the protic NHC complex
is air sensitive in solution. In the 1H NMR spectrum for this
complex the N-H proton exhibits a singlet at δ 10.89 ppm
Suprisingly, an N-carbamoyl NHC reported in 2002 was
described as being hydrolytically stable (Figure 4).8 In this
case, the carbonyl carbon is flanked by two nitrogen atoms,
one in the imidazole ring and the other in a saturated
pyrrolidine ring. The key difference from our case is that
the lone pair from the saturated nitrogen promotes usual
amide resonance and stabilizes the carbonyl against nucleo-
philic attack. Bond lengths for this species are consistent with
˚
this proposal: a C-N bond length of 1.335 A is reported
from the carbonyl carbon to the nonaromatic nitrogen,
which is characteristic of a normal amide species.
Our protic NHC complexes are air sensitive in solution,
whereas the benzoyl NHC cationic complex is stable in solu-
tion for several days. Buriak and co-workers also reported
that several cationic complexes of type [(cod)Ir(NHC)(PR3)]-
PF6 lacking N-H substitutions are insensitive to air in solution.11
(7) (a) Bonati, F.; Burini, A.; Pietroni, B. R.; Bovio, B. J. Organomet.
Chem. 1991, 408, 271. (b) Bovio, B.; Burini, A.; Pietroni, B. R. J. Organomet.
Chem. 1993, 452, 287.
(8) Batey, R. A.; Shen, M.; Lough, A. J. Org. Lett. 2002, 4, 1411.
(9) (a) Perrin, L.; Clot, E.; Eisenstein, O.; Loch, J.; Crabtree, R. H.
Inorg. Chem. 2001, 40, 5806. (b) Chianese, A. R.; Li, X.; Janzen, M. C.;
Faller, J. W.; Crabtree, R. H. Organometallics 2003, 22, 1663. (c) Kelly,
R. A., III; Clavier, H.; Giudice, S.; Scott, N. M.; Stevens, E. D.; Bordner, J.;
Samardjiev, I.; Hoff, C. D.; Cavallo, L.; Nolan, S. P. Organometallics 2007,
27, 202.
(10) Fife, T. H. Acc. Chem. Res. 1993, 26, 325.
(11) Vazquez-Serrano, L. D.; Owens, B. T.; Buriak, J. M. Chem.
Commun. 2002, 2518.

Note
Organometallics, Vol. 29, No. 21, 2010 5731
Scheme 5. Formation of Cationic Benzoyl and Protic NHC Complexes
Figure 4. An N-carbamoyl NHC species reported by Batey et al.
of the N-benzoyl imidazolium salt in a manner analogous
to the traditional N-alkyl and -aryl-substituted salts. The
resulting species are stable but cleave upon exposure to
nucleophilic MeOH solvent to provide the protic NHC
complex.
Figure 3. ORTEP diagram of 7 with 30% probability ellipsoids.
The hexafluorophosphate anion is removed for clarity. Selected
bond lengths (A): Ir(1)-C(1) 2.004, Ir(1)-P(1) 2.322, N(2)-C-
(2) 1.459, N(2)-C(1) 1.342, N(1)-C(1) 1.357, Ir(1)-C(35)
2.209, Ir(1)-C(32) 2.209, Ir(1)-C(31) 2.190, Ir(1)-C(36)
2.198, C(32)-C(31) 1.38(1), C(35)-C(36) 1.397.
Acknowledgment. We acknowledge support from the
U.S. DOE catalysis program under grant DE-FG02-
84ER13297. We thank Professor Scott Miller (Yale) for
helpful discussions and Professor Nilay Hazari (Yale)
for experimental assistance. Additionally we thank Dr.
Chris Incarvito (Yale) for assistance in crystallographic
analysis.
˚
The protic NHC ligand thus promotes air sensitivity by an
unknown mechanism.
Conclusion
Supporting Information Available: Experimental procedure
and NMR spectral data for all compounds, including the
methanolysis of complex 3. X-ray crystal data for 2, 3, and 7.
This material is available free of charge via the Internet at http://
pubs.acs.org.
We present a synthetic strategy for the synthesis of protic
NHC species via benzoyl N-heterocyclic carbene intermediates.
Our N-benzoyl NHCs can be prepared by deprotonation