Tuning the reactivity of dirhodium(II) complexes with axial N-heterocyclic carbene ligands: The arylation of aldehydes

Article abstract of DOI:10.1002/anie.200700924

(Chemical Equation Presented) Efficient dinuclear catalysts: A complex of {Rh₂(OAc)₄} with two N-heterocyclic carbenes (NHCs) at the axial positions catalyzes the arylation of aldehydes (see picture; R = alkyl, aryl). DFT calculations reveal subtle stereoelectronic effects resulting from the NHC coordination to the dirhodium(II) complex and suggest that complexes with one axial NHC ligand are the catalytically active species.

Full text of DOI:10.1002/anie.200700924

Communications
DOI: 10.1002/anie.200700924
Catalytic Arylation
Tuning the Reactivity of Dirhodium(II) Complexes with Axial
N-Heterocyclic Carbene Ligands: The Arylation of Aldehydes**
Pedro M. P. Gois,* Alexandre F. Trindade, Luís F. Veiros, Vania AndrØ, M. Teresa Duarte,
Carlos A. M. Afonso, Stephen Caddick, and F. Geoffrey N. Cloke
Dirhodium(II) complexes are highly popular in organic
synthesis due to their remarkable efficiency in the generation
Table 1: Ligand evaluation study.
[
1,2]
of carbenoids from diazo compounds.
These complexes
contain a RhÀRh bond, two axial ligands, and four bridging
ligands which control the electrophilicity of the catalyst and,
in some cases, provide a mechanism for inducing asymmetry.
The two axial ligands (normally solvent molecules) form a
weaker bond with the metal atoms than do the bridging
ligands and are thought to play a less important role in
[
1,2]
catalysis, as they are easily displaced.
Despite their unique
structural and electronic characteristics and their widespread
utilization in the generation of carbenoids from diazo
[
1,2]
compounds,
the use of dirhodium(II) complexes as cata-
[
3]
lysts in other reactions is somewhat infrequent. We, there-
fore, embarked on a study to establish whether these
complexes could provide a source of Rh for other trans-
[a]
[b]
Entry ComplexLigand
Solvent
T
t
Yield
[%]
I
[
c]
[8C] [h]
formations by simple coordination with the appropriate axial
ligand. Among all the possibilities, N-heterocyclic carbene
1
2
3
4
5
6
7
8
9
0
–
NHC-4
–
DME/H O
90
90
90
90
90
90
90
90
60
60
20
20
0.5 94
1
1
20
20
20
24
24
0.5 94
0.5 90
0.5 n.r.
trace
n.r.
2
[Rh (OAc) ]
[Rh (OAc) ] NHC-4
[Rh (OAc) ] NHC-5
[Rh
[Rh (OAc) ] NHC-7
[Rh (OAc) ] NHC-8
[Rh
[Rh (OAc) ] NHC-4
[Rh (pfb) ]
[Rh (pfb) ]
[Rh (pfb) ]
DME/H O
2
4
2
(
NHC) ligands seemed to offer good potential, as they are
DME/H O
2
4
2
neutral, two-electron-donating (s-donating) ligands with
DME/H O
99
97
2
4
2
[
4]
negligible p backbonding.
2
(OAc)
4
]
NHC-6
DME/H
2
O
DME/H O
n.r.
trace
37
n.r.
83
To test our hypothesis, we focused on the synthesis of
diaryl methanols, which are key structural elements in an
2
4
2
DME/H O
2
4
2
[
5,6]
2
(OAc)
4
]
PPh
3
DME/H O
2
array of pharmacologically active compounds.
ing our study with the arylation of aldehyde 1, we found that
combining [Rh (OAc) ]with NHCs prepared in situ by
On initiat-
DME/H O
2
4
2
1
NHC-4
NHC-4
NHC-4
NHC-4
DME/H O
2
4
2
2
4
11
12
tert-amyl alcohol 60
tert-amyl alcohol 40
tert-amyl alcohol 40
2
4
deprotonation of the corresponding imidazolium or imidazo-
2
4
13
RhCl3
[
*] Dr. P. M. P. Gois, A. F. Trindade, Prof. Dr. L. F. Veiros, V. AndrØ,
Prof. Dr. M. T. Duarte, Prof. Dr. C. A. M. Afonso
CQFM and CQE
[a] Compounds 4 (IPrHCl), 5 (SIPrHCl), 6 (IMesHCl), 7 (ItBuHCl), and 8
(IAdHCl) are precursors to the ligands NHC-4, NHC-5, NHC-6, NHC-7,
and NHC-8, respectively. [b] DME/H O (0.5:0.12 mL). [c] Yields of
2
Departamento de Engenharia Química e Biológica
Complexo I, Instituto Superior TØcnico
Av. Rovisco Pais 1, 1049-001 Lisboa (Portugal)
Fax: ( +351)218-417-122
product obtained after purification by preparative thin-layer chromatog-
raphy; n.r.=no reaction.
E-mail: pedrogois@ist.utl.pt
linium salts (Table 1, entries 3–5) gave the secondary alcohol
Dr. P. M. P. Gois, Prof. Dr. S. Caddick
Department of Chemistry
3
almost quantitatively in less than an hour. Interestingly, all
University College London
the imidazolium and imidazolinium salts with N-aryl sub-
20 Gordon Street, London WC1HOAJ (UK)
stituents afforded the desired product despite having different
[
7]
Dr. P. M. P. Gois, Prof. Dr. F. G. N. Cloke
Department of Chemistry
School of Life Sciences, University of Sussex
Falmer, Brighton BN19QJ (UK)
steric and electronic profiles, whereas salts with bulky N-
alkyl substituents did not react at all, even after prolonged
heating (Table 1, entries 6 and 7). Triphenylphosphine per-
formed better than NHCs with bulky N-alkyl substituents,
although a yield of only 37% of the alcohol was obtained
[
**] The Fundaç¼o para a CiÞncia e Tecnologia and FEDER (POCTI/QUI/
60175/2004, POCI/QUI/58791/2004, SFRH/BPD/18624/2004, and
(Table 1, entry 8).
SFRH/BD/30619/2006) are thanked for financial support.
II
A study of Rh complexes led to the identification of
Rh (pfb) ](pfb = perfluorobutyrate) as the most efficient
Supporting Information for this article (experimental and compu-
tational details, atomic coordinates, and additional information for
the optimized species) is available on the WWW under http://
www.angewandte.org or from the author.
[
2
4
catalyst: in combination with the protic solvent tert-amyl
alcohol this complex allowed the formation of alcohol 3 in
5
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Angewandte
Chemie
higher yields at temperatures as low as 408C without the use
[
8]
of water (Table 1, entries 9–12).
We tested the optimized catalytic system in the arylation
of aryl and alkyl aldehydes (Table 2, entries 1–11). In most
cases the reaction proceeded with remarkable efficiency (up
Table 2: Arylation of alkyl and aryl aldehydes.
[
a]
Entry
R
R’
Product Method
T
t
Yield
[
b]
[8C] [h] [%]
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
C6H5
4-MeC
4-ClC H4
4-MeOC H4
4-PhC H4
2-Naphthyl
4-CNC H4
C6H5
C6H5
Cy
H
H
H
H
H
H
H
MeO
F
H
H
H
H
10
11
12
3
13
14
15
3
16
17
18
3
19
15
3
A
A
A
A
A
A
A
A
A
A
A
B
B
B
B
B
B
B
60
60
1
4
99
91
6
H
4
60 0.7 95
40 0.5 90
6
6
60
80
80
60
60
60
60
90
90
90
90
90
90
90
1
5
5
2
2
3
3
1
3
6
1
6
6
6
99
94
80
95
67
88
77
87
96
78
95
96
95
99
6
6
1
1
1
1
1
1
1
1
1
n-C H
7
15
4-MeOC H4
(3,4-OCH O)C H
3
4-CNC H4
C6H5
C6H5
C6H5
6
2
6
H
6
MeO
Me
F
11
16
18
n-C H
H
7
15
[
18]
Figure 1. ORTEP diagrams of the dirhodium complexes 20 (top) and
1 (bottom). Ellipsoids are set at 30% probability. Solvent molecules
[
a] Method A: [Rh (pfb) ] (3.0 mol%), 4 (3.0 mol%), KOtBu (1.0 equiv),
2 4
2
tert-amyl alcohol. Method B: 20 (1.0 mol%), KOtBu (10 mol%), tert-
amyl alcohol. [b] Yields of product obtained after purification by
preparative thin-layer chromatography.
and hydrogen atoms are omitted. Selected bond lengths [Š] for 20:
Rh1ÀRh2 2.4731(3), Rh1ÀC9 2.228(3), Rh2ÀC36 2.244(3); for 21: Rh1À
Rh1a 2.4627(12), Rh1ÀC9 2.244(7). All coordination angles around the
Rh centers are near 908.
to 99% yield of isolated product) under mild conditions. The
methodology proved to have a noteworthy tolerance to
functional groups, although it is highly sensitive to electronic
effects. In contrast to other catalytic systems, electron-
donating groups at the para position of the aryl aldehyde
clearly activate the aldehyde, whilst strongly electron-
withdrawing groups deactivate the aldehyde (Table 2,
entries 4 and 7, respectively).
quantity of catalyst (1.0 mol% for method B instead of
3.0 mol% for the in situ method A) and base. Particularly
noteworthy is the finding that in the synthesis of 11 using
complex 20 we were able to isolate the complex with only one
NHC ligand NHC-4 attached to the {Rh (OAc) } moiety
(75% of the initial quantity of complex 20 used). This isolated
mono-NHC complex efficiently catalyzed the arylation of p-
tolualdehyde, affording the alcohol 11 in 95% yield.
[
9]
2
4
In view of these results, we attempted the synthesis of the
dirhodium(II) complex bearing NHCs at the axial posi-
[
10]
tions. Thus, we generated NHC-4 in situ in the presence of
Rh (OAc) ]and isolated complex 20, which has NHC ligands
Mass-spectrometry analysis of the crude mixture of a
similar arylation reaction catalyzed by complex 20 identified
the mono-NHC species [(NHC-4)Rh (OAc) ]and [Rh 2-
[
2
4
at both axial positions (72% yield of isolated product).
2
4
[
11]
Figure 1 shows the molecular structure of 20. The RhÀRh
bonding distance and the RhÀC(carbene) distances are within
the ranges of values found in related compounds with a
(OAc) ](complexed with a solvent molecule). The presence
4
of [Rh (OAc) ]in the crude reaction mixture suggests that the
2
4
loss of catalyst (25%) could be due to decomplexation of 4
[
12]
II
II
carboxylate cage structure.
Each Rh atom displays an
from [Rh (OAc) ]rather than disproportionation of the Rh
2
2
almost perfect octahedral coordination geometry, with RhÀO
dimer. To test this hypothesis we prepared the complex
distances of 2.04–2.06 Š and coordination angles of around
[(NHC-5) Rh (OAc) ] (21; 60% yield of isolated product),
2
2
4
9
08.
The isolated complex proved to be a catalyst for the
with saturated NHC ligands, and determined its molecular
structure (Figure 1). The analogous complexes 20 and 21
exhibit different N-C-C-N torsion angles (0.20(2) and
8.35(2)8) and different NÀC (1.388(4)/1.391(4) and
arylation of aldehydes (Table 2, entries 12–18), yielding the
alcohols in high yields with a considerable reduction of the
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Communications
I
1
1
.486(10)/1.469(10) Š) and CÀC distances (1.343(4) and
between the calculated charges does not support a clear Rh /
[
11]
III
.495(12) Š).
Under the same reactions conditions as for complex 20,
Rh separation. The same trend is observed for complexes
with NHC-6 and NHC-7.
complex 21 afforded the alcohol 11 in 95% yield. We were
able to recover the mono-NHC complex [(NHC-5)Rh2-
Coordination of NHC-4 results in a perfect structural
match (Figures 1 and 2). The isopropyl groups fit in between
the OAc bridges, and the carbene ring remains in an eclipsed
(
OAc) ]in excellent yield ( > 97%). These results, along
4
with the observation that no alcohol was formed with the
III
efficient Rh /NHC catalytic system developed by Fürstner
[
6]
II
et al. (Table 1, entry 13), clearly indicate that our Rh –NHC
complex maintains its integrity under these reaction con-
I
III
ditions and does not disproportionate into Rh and Rh
species.
We investigated complexes with only one axial NHC
ligand, [Rh (OAc) (NHC)], as catalysts in the reaction by
2
4
[
13]
performing density functional calculations
on four opti-
complexes with NHC-4, NHC-6, and
NHC-7, and the bare metallic fragment [Rh (OAc) ]for
[
14]
mized structures:
2
4
[
15]
comparison. The stability of the carbene complexes can be
evaluated by the energy variation (DE) of the complexation
[
16]
reaction, and the values obtained indicate that all com-
plexes are stable relative to the isolated reactants. However,
the values of DE obtained for NHC-4 and NHC-6 (À19 and
Figure 2. Optimized structure (B3PW91) for [(NHC-4)Rh
NHC is depicted in darker gray), and its LUMO (right).
(OAc) ] (left;
4
2
À1
À26 kcalmol , respectively, are quite low by comparison
À1
with that obtained for NHC-7 (À8 kcalmol ), which may
help explain the poor reactivity of NHC-7 (Table 1, entry 6).
The calculated RhÀC distances for NHC-4 and NHC-6 are
conformation, which is different from the bisecting arrange-
ment observed for the species with N-methyl substituents.
[
9]
0
.2 Š shorter than for NHC-7. This difference reflects the
The stereochemical protection of one Rh center provided by
the NHC ligand may help to stabilize the complex. Further-
more, the significant contribution from the terminal Rh
center to the LUMO of the complex (Figure 2) affords a
coordination position for reactant molecules.
RhÀNHC bond strength, as also shown by the corresponding
[
17]
Wiberg indices (WI) of 0.40 (NHC-4), 0.41 (NHC-6), and
0
.32 (NHC-7).
Coordination of the NHC ligand is essentially established
by s donation from the carbene lone pair to the lowest
In summary, we have presented an efficient catalytic
system for the arylation of aldehydes based on readily
available and highly versatile dirhodium(II) complexes and
NHC ligands. The near-perfect structural match between
[Rh (OAc) ]and NHC-4 found in the X-ray structure of 20
unoccupied molecular orbital (LUMO) of {Rh (OAc) }. This
2
4
is a Rh–Rh antibonding orbital (s*) derived from the out-of-
phase combination of two dz orbitals (see the Supporting
2
Information). Thus, the formation of a RhÀNHC bond
2
4
corresponds to electron transfer from the carbene to the
metallic fragment, and to the population of a Rh–Rh
antibonding orbital. Accordingly, the RhÀRh bond length
and in the calculated structure of [(NHC-4)Rh (OAc) ] , as
2 4
well as the electronic structure of this species, may explain the
catalytic performance of this system. This study highlights a
new reaction mode for dirhodium(II) dimers involving the
possible transmetalation of the aryl group from boronic acids
to dirhodium(II) complexes. Further experimental and com-
putational studies will be conducted in order to extend the
scope of these method and to fully elucidate the reaction
mechanism.
increases from 2.36 Š in isolated [Rh (OAc) ]complex to
2
4
2
.44 Š in all the NHC complexes, and reaches 2.47 Š in
complex 20 (Figure 1), where both axial positions are
occupied by NHC ligands. A more subtle tuning is revealed
by the Rh–Rh Wiberg indices of 0.52 (NHC-4 and NHC-6)
and 0.58 (NHC-7), which indicate that this bond is weaker
than in isolated [Rh (OAc) ](WI = 0.78), with the effect
2
4
being more clear-cut for stronger RhÀNHC bonds (NHC-4
Received: March 1, 2007
Revised: April 19, 2007
Published online: June 25, 2007
and NHC-6).
Electron donation from the NHC ligand affects the
[
19]
charge of the {Rh (OAc) } moiety (À0.28 (NHC-4), À0.29
2
4
Keywords: aldehydes · arylation · carbene ligands ·
(
NHC-6), and À0.23 (NHC-7)), and the weaker bond for
.
homogeneous catalysis · rhodium
NHC-7 corresponds to an electron-poorer metallic fragment.
The same effect is observed for the atomic charge of the Rh
centers. These values are 0.74 (terminal Rh) and 0.89 (RhNHC
)
[
1]a) M. P. Doyle, M. A. McKervey, T. Ye in Modern Catalytic
Methods for OrganicSynthesis with Diazo Compounds , Wiley-
Interscience, New York, 1998; b) Y. Lou, T. P. Remarchuk, E. J.
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Cotton, E. Hillard, C. A. Murillo, J. Am. Chem. Soc. 2002, 124,
5658 – 5660.
for NHC-4, while in isolated [Rh (OAc) ]the Rh charge is
2
4
0
.92. More importantly, the asymmetry in the Rh charges
calculated for NHC-4 indicates an electron-richer terminal
Rh center and shows a trend towards a mixed-oxidation-state
[
20]
complex, as proposed previously, although the difference
5
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Angewandte
Chemie
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2]a) H. M. L. Davies, R. E. J. Beckwith, Chem. Rev. 2003, 103,
861 – 2903; b) M. P. Doyle, J. Org. Chem. 2006, 71, 9253 – 9260;
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a = 11.256(2), b = 12.538(3), c = 15.367(5) Š, a = 69.63(2), b =
3
2
84.172(2), g = 77.614(3)8, V= 1984.7(9) Š , Z = 2, T= 150 K,
À3
À1
1calcd = 1.244 Mgm , m = 0.471 mm , F(000) = 774. Data were
collected with a Bruker AXS KAPPA APEX II diffractometer
using graphite-monochromated MoKa radiation (l = 0.71069 Š).
Structures were solved by direct methods (SIR97). Non-hydro-
gen atoms were refined anisotropically and hydrogen atoms
were inserted in calculated positions as riding on the parent
carbon atom (WINGX). Of 56487 reflections for complex 20,
14673 were independent (Rint = 0.0492); 887 variables were
refined to final R1(I>2s(I)) = 0.0434, wR2(I>2s(I)) = 0.0965,
R1(all data) = 0.0815, wR2(all data) = 0.1065, GOF = 1.037. For
3
[
4641 – 4644; c) T. Washio, S. Nakamura, M. Anada, S. Hashi-
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4]a) F. E. Hahn, Angew. Chem. 2006, 118, 1374 – 1378; Angew.
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Angew. Chem. 2002, 114, 1342 – 1363; Angew. Chem. Int. Ed.
complex 21, of 30833 reflections, 4408 were independent (Rint =
0.0711); 411 variables were refined to final R1(I>2s(I)) =
0.0675, wR2(I>2s(I)) = 0.1714, R1(all data) = 0.0945, wR2(all
data) = 0.2028, GOF = 1.170. CCDC-639254 (20) and CCDC-
644438 (21) contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/data_request/cif.
2
002, 41, 1290 – 1309; c) “N-Heterocyclic Carbenes in Transition
Metal Catalysis”: Topics in Organometallic Chemistry, Vol. 21
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(
Heterocyclic Carbenes in Synthesis (Ed.: S. P. Nolan), Wiley-
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Molecules, Oxford University Press, New York, 1989.
[14]The optimizations were performed at the B3PW91/VDZP level
with the Gaussian98 package. Details and references are
provided as Supporting Information.
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[15]The calculated structures are depicted in the Supporting
Information.
[
[
[16]Calculated as the difference between the energy of the two
isolated fragments {Rh (OAc) } and NHC and the energy of the
2
4
final species [Rh (OAc) (NHC)].
2 4
[17]a) K. B. Wiberg, Tetrahedron 1968, 24, 1083; b) Wiberg indices
are electronic parameters that are related to the electron density
between atoms. They can be obtained from a natural population
analysis and provide an indication of the bond strength.
[18]ORTEP3 for Windows: L. Farrugia, J. Appl. Crystallogr. 1997,
30, 565.
[19]All charges reported result from a natural population analysis.
See the Supporting Information for details.
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1171; b) E. Nakamura, N. Yoshikai, M. Yamanaka, J. Am. Chem.
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[
11]Crystallographic data for 20: C H N O Rh , M = 1495.55,
8
3
108
4
8
2
r
3
¯
orange crystals, 0.18 ” 0.16 ” 0.12 mm , triclinic, space group P1,
a = 12.6540(2),
b = 18.2140(3),
b = 101.3890(10),
c = 19.1580(3) Š,
g = 101.8950(10)8,
a =
V=
m =
1
4
0
03.5840(10),
3
À3
057.10(11) Š , Z = 2, T= 150 K, 1calcd = 1.224 Mgm
,
À1
.460 mm , F(000) = 1576. For 21: C H N O Rh, M = 743.7,
4
2
44
2
4
r
3
¯
orange crystals, 0.15 ” 0.11 ” 0.10 mm , triclinic, space group P1,
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