Electronically tunable N-heterocyclic carbene ligands: 1,3-diaryl vs. 4,5-diaryl substitution

Article abstract of DOI:10.1039/b914732b

The catalytic activity of iridium-mediated transfer hydrogenation is readily tuned by electronic variation of the ligated tetraaryl-N-heterocyclic carbene and the installation of electron donating groups on the N-aryl substituents is more important than o

Full text of DOI:10.1039/b914732b

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Electronically tunable N-heterocyclic carbene ligands: 1,3-diaryl
vs. 4,5-diaryl substitutionw
James W. Ogle and Stephen A. Miller*
Received (in College Park, MD, USA) 6th August 2009, Accepted 18th August 2009
First published as an Advance Article on the web 2nd September 2009
DOI: 10.1039/b914732b
The catalytic activity of iridium-mediated transfer hydrogena-
tion is readily tuned by electronic variation of the ligated
tetraaryl-N-heterocyclic carbene and the installation of electron
donating groups on the N-aryl substituents is more important
than on the C-aryl substituents for effecting catalytic enhancement.
bidentate-NHC iridium(III) catalysts tested by Crabtree and
co-workers (TOF up to 50 000 hꢀ1).29,31 Note that catalyst 3b
is 65% more active than 3c, suggesting that electronic control
at the 1,3 (nitrogen) positions is more effective than at the 4,5
(carbon) positions of the NHC.
Fig. 1 plots the log10 of the turnover frequency (in hꢀ1) of
3a–e against the average carbonyl stretching frequency of
the corresponding Ir carbonyl complexes 4a–e. The linear
relationship observed highlights the catalytic control that
can be exerted via precise electronic tuning of the NHC ligand.
Generally, electron donating groups (ꢀOMe) enhance the
catalytic activity compared to electron withdrawing groups
(ꢀF). While much less electron-rich and less active, the well-
known IMesIr(COD)Cl catalyst has an activity in accord with
the apparent linear trend.2,32
Numerous research groups—notably those of Crabtree,
Herrmann, and Nolan—have employed various methods for
characterizing the electronic properties of N-heterocyclic
carbenes (NHCs),1–7 which are proven to be a privileged class
of ancillary ligand in metal-mediated catalysis.8–13 Prominent
among these methods is the analysis of infrared carbonyl
stretching frequencies in NHC–metal carbonyl species.
Comparison of the IR carbonyl stretches in iridium carbonyl
NHCs to Tolman electronic parameters, based on nickel
carbonyl NHCs, has been achieved with a high degree of
correlation. Most of these studies have been conducted on
1,3-disubstituted NHCs (nitrogen substitution), although a
few 4,5-disubstituted NHCs (carbon substitution) have been
investigated.2,3,5,14–21 Nonetheless, we have a limited under-
standing of the influence that 4,5-disubstitution bears on the
electronic and catalytic properties of NHCs compared to
1,3-disubstitution.22 The prospect of holistic electronic
tuning23 of NHCs is alluring.
Analysis of the NMR spectra for the complexes 3a–e can also
be used as an electronic assessment. As the iridium metal gains
electron density, the metal–alkene bond distances (of Ir–COD)
decrease, the sp2 C–H bond distances increase and therefore lose
shielding, causing a downfield shift of the 1H NMR peaks in the
vinylic region. A linear relationship was found between the TOF
(in hꢀ1) and the chemical shift (in ppm) of the 1,5-cyclooctadiene
protons in the alkene bound trans to the carbene:
TOF = ꢀ14 300 (d) + 62 600 (with R2 = 0.852).w
The complexes 3a–e were also analyzed via Hammett
Recently, we published a strategy based on aldimine
coupling for the facile access of 1,2,3,4-tetraaryldiimines,
precursors to 1,3,4,5-tetrarylimidazolium salts.24 Scheme 1
depicts our straightforward synthetic route from electronically
prescribed benzaldehydes and anilines to 1,5-cyclooctadiene
iridium NHC complexes (3a–e) or the corresponding carbonyl
complexes (4a–e). Surprisingly, comparison of the average IR
carbonyl stretch (nCOav) with those of over thirty literature
Ir–NHC species indicated that the NCH ligands of 4a–e are
among the most electron-rich25 developed so far; they also
exhibited the widest range of electronic character for NHCs
prepared via a single synthetic approach.1–4,7,17
correlations,
a reasonable approach because the para
substituents impact the electronics, but likely have a minimal
steric effect.4 We compared transfer hydrogenation rates for
the 1,3-diaryl series 3a, 3b, and 3d and the 4,5-diaryl series 3a,
3c, and 3e. Fig. 2 illustrates that the correlations with smeta
(R2 = 0.810, 0.993) and sI (R2 = 0.619, 0.983) were superior
to that with spara (R2 = 0.506, 0.064), indicating that inductive
A robust system for testing the viability of new Ir–NHC
catalysts is the transfer hydrogenation of acetophenone.21,26–30
For this reaction, complexes 3a–e represent the most active
mono-NHC iridium(I) catalysts known. Complexes 3a and 3b
exhibited the highest turnover frequencies (1080 and 1240 hꢀ1
,
respectively) but are still less active than a few specialized
The George and Josephine Butler Laboratory for Polymer Research,
Department of Chemistry, University of Florida, Gainesville,
FL 32611-7200, USA. E-mail: miller@chem.ufl.edu;
Fax: +1-352-392-9741; Tel: +1-352-392-7773
w Electronic supplementary information (ESI) available: Synthetic
details, NMR spectra, infrared data, transfer hydrogenation data,
and Hammett correlation data. See DOI: 10.1039/b914732b
Scheme 1 Synthesis of iridium carbonyl carbene complexes 4a–e.
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for the transfer hydrogenation of ketones: the rate-limiting
step involves transfer of an iridium hydride to the carbonyl
carbon of a pendant ketone and net loss of electron density at
iridium as the transition state is approached.
Anomalously, catalyst 3b proved to be the most active
catalyst studied, despite its inductively withdrawing
ꢀC6H4OMe aryl groups in the 1,3 positions. Perhaps the
modest fits to smeta and sI (R2 = 0.810, 0.619) indicate that
resonance effects—and not inductive effects alone—have
significance for substituents at the 1,3 positions. A para-
methoxy group is a good p-donor via resonance and probably
contributes some electron density this way to iridium, lowering
the transition state energy.
Computational studies support the conclusion that
electronic variation of the 1,3-N-aryl groups is more
consequential than electronic variation of the 4,5-C-aryl
groups. The free carbenes from structures 4a–e were subjected
to a density functional theory study at the B3LYP 6-31G*
level. The carbene ground state structures were derived from
the X-ray crystal structures of the corresponding NHC–AgCl
complexes 5a–e,24 following removal of the AgCl portion.
Fig. 3 shows the resulting electrostatic potential maps along
with the calculated electrostatic charge at the carbene carbon.
These results clearly indicate that electronic perturbation of
the 4,5-C-aryl groups is minimally effective, whereas perturbation
of the 1,3-N-aryl groups significantly changes the calculated
charge on the 2-carbon of the heterocycle. Specifically,
addition of para F substituents to the 1,3-N-aryl groups results
in a decrease of 0.049 eꢀ while addition of para-methoxy
substituents to the 1,3-N-aryl groups results in an increase
of 0.023 eꢀ at the carbene carbon. Similar additions to the
4,5-C-aryl groups result in a minute change of 0.001 eꢀ.
In conclusion, we developed a series of five iridium COD
1,3,4,5-tetraaryl N-heterocyclic carbene complexes 3a–e, all of
which excel known 1,3-diaryl-NHC analogues for catalytic
transfer hydrogenation of ketones. Electronic tuning was
possible by variation of the para-C6H4X aryl groups in the
1,3 and 4,5 positions of the NHC. The catalytic turnover
frequencies correlated strongly to the average nCO stretches
found in the corresponding iridium carbonyl complexes 4a–e.
Hammett plots suggested that inductive effects are generally
more important than resonance effects—probably a result of
poor p overlap between the aryl groups and the heterocycle.
Electronic variation of the 1,3-aryl groups seemed to have a
noticeably greater effect on turnover frequency than variation
of the 4,5-aryl groups. In general, electron s-withdrawing
methoxy and fluorine substituents hamper catalysis. The
exception is complex 3b, which appears to be the most active
mono-NHC iridium-based transfer hydrogenation catalyst.
Ostensibly, its para-C6H4OMe aryl groups in the 1,3 positions
contribute electron density via resonance and assuage the loss
of electron density at iridium during the rate-limiting transfer
of hydride to a ligated ketone.
Fig. 1 Catalytic turnover by 3a–e in the transfer hydrogenation of
acetophenone with acetone. The log10 of the TOF (in hꢀ1) is linearly
proportional to the average IR carbonyl stretch of the corresponding
Ir carbonyl complexes 4a–e. TOFs are determined by 1H NMR at
t = 1 hour for two reactions each; IMesIr(COD)Cl values are from
ref. 2 and 32; error bars represent one standard deviation for 3 to 4
measurements of nCO
.
effects are more important than resonance effects for this
system. An explanation for this is that the aryl rings are not
coplanar with the central heterocycle and resonance effects are
correspondingly diminished, as suggested by X-ray crystallo-
graphy of the cognate NHC–AgCl complexes 5a–e.24 The
average dihedral angles for the 1,3-aryl rings are 681, 731,
601, 751, and 671, while the average dihedral angles for the
4,5-aryl rings are 671, 691, 471, 701, and 681 for 5a–e, respectively.
For the smeta and sI analyses, the slopes for the 1,3-diaryl
series (r = ꢀ1.65, ꢀ0.99, respectively) are somewhat greater
in magnitude than those for the 4,5-diaryl series (r = ꢀ1.06,
ꢀ0.73, respectively). This suggests that substitution at the
1,3 positions of NHCs is more effective than substitution at
the 4,5 positions for electronic tuning. However, this conclusion
is not unequivocal since data sets were synthetically restricted
and regression analyses for 1,3 substitution were modest
(R2 = 0.810, 0.619). Nonetheless, the negative r values
validate a recent mechanistic proposal by Bi and co-workers35
Indeed, the substituents of N-heterocyclic carbenes can be
electronically tuned to optimize catalysis. With just a handful
of catalysts, we have demonstrated the importance of
substitution at all four positions of imidazolylidene NHCs
and we believe that further optimization is certainly possible
with this and other catalytic systems.
Fig. 2 Hammett plots for the transfer hydrogenation of aceto-
phenone by 3a–e. Rates are determined by 1H NMR conversion at
t = 1.0 hour (average of two reactions) and are plotted as log10(k/kH)
vs. spara (circles), smeta (squares), or sI (diamonds).33,34 All linear fits
include the point at 0,0, R2 values are given, blue = 1,3-diaryl X0, and
green = 4,5-diaryl X.
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6 G. D. Frey, C. F. Rentzsch, D. von Preysing, T. Scherg,
M. Muhlhofer, E. Herdtweck and W. A. Herrmann,
J. Organomet. Chem., 2006, 691, 5725–5738.
7 A. Furstner, M. Alcarazo, H. Krause and C. W. Lehmann, J. Am.
Chem. Soc., 2007, 129, 12676–12677.
8 W. A. Herrmann, Angew. Chem., Int. Ed., 2002, 41, 1290–1309.
9 F. Boeda and S. P. Nolan, Annu. Rep. Prog. Chem., Sect. B, 2008,
104, 184–210.
10 F. E. Hahn and M. C. Jahnke, Angew. Chem., Int. Ed., 2008, 47,
3122–3172.
11 R. J. Lowry, M. K. Veige, O. Clement, K. A. Abboud, I. Ghiviriga
and A. S. Veige, Organometallics, 2008, 27, 5184–5195.
12 S. Dıez-Gonzalez, N. Marion and S. P. Nolan, Chem. Rev., 2009,
109, 3612–3676.
13 M. Poyatos, J. A. Mata and E. Peris, Chem. Rev., 2009, 109,
3677–3707.
14 A. J. Arduengo III, J. R. Goerlich, R. Krafczyk and
W. J. Marshall, Angew. Chem., Int. Ed., 1998, 37, 1963–1965.
15 G. Altenhoff, R. Goddard, C. W. Lehmann and F. Glorius, J. Am.
Chem. Soc., 2004, 126, 15195–15201.
16 A. J. Arduengo III, F. Davidson, H. V. R. Dias, J. R. Goerlich,
D. Khasnis, W. J. Marshall and T. K. Prakasha, J. Am. Chem.
Soc., 1997, 119, 12742–12749.
17 A. R. Chianese, A. Kovacevic, B. M. Zeglis, J. W. Faller and
R. H. Crabtree, Organometallics, 2004, 23, 2461–2468.
18 E. Cetinkaya, P. B. Hitchcock, H. Kucukbay, M. F. Lappert and
S. Al-Juaid, J. Organomet. Chem., 1994, 481, 89–95.
19 G. Song, Y. Zhang and X. Li, Organometallics, 2008, 27,
1936–1943.
20 H. M. J. Wang and I. J. B. Lin, Organometallics, 1998, 17, 972–975.
21 H. Turkmen, T. Pape, F. E. Hahn and B. Cetinkaya, Organo-
metallics, 2008, 27, 571–575.
22 S. Leuthaußer, V. Schmidts, C. M. Thiele and H. Plenio,
Chem.–Eur. J., 2008, 14, 5465–5481.
23 C. Prasang, B. Donnadieu and G. Bertrand, J. Am. Chem. Soc.,
2005, 127, 10182–10183.
24 J. W. Ogle, J. Zhang, J. H. Reibenspies, K. A. Abboud and
S. A. Miller, Org. Lett., 2008, 10, 3677–3680.
25 V. Lavallo, Y. Canac, C. Prasang, B. Donnadieu and G. Bertrand,
Angew. Chem., Int. Ed., 2005, 44, 5705–5709.
Fig. 3 Calculated (DFT B3LYP 6-31G*) electrostatic charge on the
2-carbon of the free carbenes excised from NHC–AgCl complexes
5a–e.
26 X. Wu, D. Vinci, T. Ikariya and J. Xiao, Chem. Commun., 2005,
4447–4449.
27 M. Miecznikowski and R. H. Crabtree, Organometallics, 2004, 23,
629–631.
28 D. Gnanamgari, E. L. O. Sauer, N. D. Schley, C. Butler,
C. D. Incarvito and R. H. Crabtree, Organometallics, 2009, 28,
321–325.
This research was supported by the National Science
Foundation (CAREER CHE-0824305) and the University of
Florida.
29 M. Albrecht, J. R. Miecznikowski, A. Samuel, J. W. Faller and
R. H. Crabtree, Organometallics, 2002, 21, 3596–3604.
30 R. Hodgson and R. E. Douthwaite, J. Organomet. Chem., 2005,
690, 5822–5831.
31 J. R. Miecznikowski and R. H. Crabtree, Polyhedron, 2004, 23,
2857–2872.
32 I. Kownacki, M. Kubicki, K. Szubert and B. Marciniec,
J. Organomet. Chem., 2008, 693, 321–328.
33 C. Hansch, A. Leo and R. W. Taft, Chem. Rev., 1991, 91, 165–195.
34 J. Bromilow, R. T. C. Brownlee, V. O. Lopez and R. W. Taft,
J. Org. Chem., 1979, 44, 4766–4770.
Notes and references
1 A. R. Chianese, X. Li, M. C. Janzen, J. W. Faller and
R. H. Crabtree, Organometallics, 2003, 22, 1663–1667.
2 R. A. Kelly III, H. Clavier, S. Giudice, N. M. Scott, E. D. Stevens,
J. Bordner, I. Samardjiev, C. D. Hoff, L. Cavallo and S. P. Nolan,
Organometallics, 2008, 27, 202–210.
3 S. Fantasia, J. L. Petersen, H. Jacobsen, L. Cavallo and
S. P. Nolan, Organometallics, 2007, 26, 5880–5889.
4 S. Leuthaußer, D. Schwarz and H. Plenio, Chem.–Eur. J., 2007, 13,
7195–7203.
5 W. A. Herrmann, J. Schutz, G. D. Frey and E. Herdtweck,
Organometallics, 2006, 25, 2437–2448.
35 S. Bi, Q. Xie, X. Zhao, Y. Zhao and X. Kong, J. Organomet.
Chem., 2008, 693, 633–638.
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5730 | Chem. Commun., 2009, 5728–5730