Imidazo[1,5-a]pyridine: A versatile architecture for stable N-heterocyclic carbenes

Article abstract of DOI:10.1021/ja0423769

The imidazo[1,5-a]pyridine skeleton provides a versatile platform for the generation of new types of stable N-heterocyclic carbenes. Rh(I) mono- (6) and biscarbenes (7) from imidazo[1,5-a]pyridin-3-ylidenes (ImPy) and derivatives such as 13 from a mesoionic carbene were synthesized and characterized. Copyright

Full text of DOI:10.1021/ja0423769

Published on Web 02/17/2005
Imidazo[1,5-a]pyridine: A Versatile Architecture for Stable N-Heterocyclic
Carbenes
Manuel Alcarazo,† Stephen J. Roseblade,† Andrew R. Cowley,‡ Rosario Ferna´ndez,§
John M. Brown,‡ and Jose´ M. Lassaletta*,†
Instituto de InVestigaciones Qu´ımicas (CSIC-US), Ame´rico Vespucio 49, E-41092 SeVille, Spain,
Departamento de Qu´ımica Orga´nica, UniVersidad de SeVilla, E-41012, SeVille, Spain,
and Chemical Research Laboratory, UniVersity of Oxford, Oxford OX1 3TA, U.K.
Received December 19, 2004; E-mail: jmlassa@iiq.csic.es
Scheme 1
N-Heterocyclic carbenes (NHCs) have emerged during the past
decade as a new type of stable compounds1,2 and as a powerful
class of C-ligands. The stabilizing properties by NHCs, expressed
by strong metal carbene bonds and slow dissociation rates, have
been key for the development of a number of applications in
catalysis.3 To exploit further the potential of NHCs as C-ligands,
it is necessary to provide additional tools for the tuning of their
electronic properties, an aspect where the more developed trivalent
phosphorus-based ligands (phosphanes, phosphites, phosphoramid-
ites, etc.) offer much higher variability.
The construction of benzannulated derivatives is a very simple
strategy to modify the properties of Arduengo’s “original” imidazol-
Table 1. Synthesis of Imidazo[1,5-a]pyridinium Salts 2a-f
2-ylidenes A,1 as was demonstrated in the benzimidazol series B.4
An interesting variation is the bipyridine-derived carbene C,5 but
this rather unstable carbene was never used as a C-ligand for
transition metals. We now wish to report on the use of the imidazo-
[1,5-a]pyridine skeleton for the synthesis of unprecedented carbenes
D and the mesoionic structures E, containing a single bridgehead
nitrogen, and the first transition-metal complexes derived therefrom.
A straighforward synthesis of alkyl derivatives 2a,b was ac-
complished by alkylation of known 1, carrying a methyl group at
C(5) for an eventual kinetic protection of the target carbene 4
(Scheme 1, Table 1, entries 1 and 2). A second approach was
designed from formamides 3c-f, which were transformed into
N-alkyl/aryl imidazo[1,5-a]pyridinium salts 2c-f by POCl3-medi-
ated cyclization. Products were isolated either as chlorides [2c, 2d-
(Cl); entries 3 and 4] or as hexafluorophosphates [2d(PF6), 2e, 2f;
entries 5-7] after anion exchange with KPF6. This second route is
more versatile, offering fewer restrictions in the nature of the N(2)R
group and involving more accessible starting materials.
respect to Arduengo’s type A carbenes, confirmed their free carbene
structure.
The properties of compounds 4 as C-ligands were investigated:
RhImPy(COD)Cl (ImPy ) Imidazo[1,5-a]pyridine-3-ylidene) com-
plexes 6 were prepared by: (a) direct metalation of carbenes 6 with
[Rh(COD)Cl]2 (Scheme 1, Table 2, entries 2, 4, and 7) or (b)
transmetalation of silver carbene complexes 5, available from
halides 2a-c and 2d(Cl) (entries 1, 3, 5, and 6). The single-crystal
X-ray analyses of 6b and 6d (Figure 1) revealed distorted square-
planar geometries (CRhCl 92.8° and 95.4°, respectively), and
marked differences in NCRh angles (6b: 132.8° versus 123.5°; 6d:
131.2° versus 124°), both attributed to steric repulsions. As in
related structures,6 1H NMR studies indicated high configurational
stability due to restricted rotation around the C(3)-Rh bond, even
for C(5)-unsubstituted derivatives such as 6c. Different behavior
was observed when 2d(PF6), 2e, or 2f (X ) PF6) were reacted
with KOtBu and [Rh(COD)Cl]2: cationic 2:1 [Rh(ImPy)2(COD)]+
The stability of the free carbenes 4 proved to be strongly
dependent on their steric environment. Thus, deprotonation of
5-unsubstituted 2c,f by NaH/KOtBu (cat.) in dry THF resulted in
the formation of a complex mixture, presumed to arise from
formation and decomposition of the desired carbene. In sharp
contrast, deprotonation of 5-substituted azolium salts 2a,b,d,e
proceeded cleanly to afford free carbenes 4a,b,d,e (Scheme 1).
These products were found to be stable for long periods at
room temperature and could be isolated as viscous oils or
amorphous solids and characterized by 1H and 13C NMR. The 13
C
resonance for C(3) of 4 (δ ) 206-209 ppm), slightly upfield with
† Instituto de Investigaciones Qu´ımicas (CSIC-US).
‡ University of Oxford.
§ Departamento de Qu´ımica Orga´nica, Universidad de Sevilla.
9
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J. AM. CHEM. SOC. 2005, 127, 3290-3291
10.1021/ja0423769 CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Synthesis of Silver and Rhodium Complexes 5, 6, and 7
Scheme 2
starting
material
yield
(%)
yield
(%)
yield
(%)a
entry
X
5
6
7
1
2
2a
I
5a
-
63
92
6a
6a
6b
6b
6c
6d
91
93
96
94
96
92
4a
-
3
2b
Br
5b
-
4
4b
-
5
2c
Cl
5c
5d
98
96
6
2dCl
2dPF6
2e
Cl
8
PF6
PF6
PF6
7d
7e
7f
71 (82)
72 (86)
84 (93)
9
10
2f
a Yield of recrystalized product. In parentheses: yield before crystal-
ization.
ring support a strong contribution of the mesoionic form I, as drawn
in 11, 12, 13, and 15.
Finally, dicarbonyl Rh complexes 16 and 17 were prepared from
6a and 13, and their ν(CO) stretching frequencies were used to
evaluate the σ-donor ability of 4 and 14. The results indicate that
these carbenes are among the strongest σ-donors in the unsaturated
series, but still weaker than the best known C-ligands.9
In conclusion, the imidazo[1,5-a]pyridine skeleton is a versatile
platform for the synthesis of new types of free NHCs and their
transition-metal complexes. The effect of electron-withdrawing or
-donating groups in ImPy ligands, and the development of applica-
tions in catalysis, is currently the object of study in our laboratories.
Acknowledgment. We thank the MEC (Grant CTQ2004-00290/
BQU) and the EC (HPRN-CT-2001-00172 and HP-CT-2001-00317)
for financial support. We thank Dr. Ju¨rgen Klankenmayer for
assistance in the crystalization of samples for X-ray structure
analysis.
Supporting Information Available: Crystallographic data for 6b,
6d, 7d, 7e, 7f, and 13, and experimental procedures (CIF, PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
Figure 1. ORTEP drawings for Rh-ImPy complexes 6d, 7e, and 13.
complexes 7d-f were obtained, even though the Rh/carbene
precursor ratio was 1:1 (Scheme 2). Good yields of compounds 7
were observed for reactions performed with the right 2:1 stoichi-
ometry, even for bulky ligands such as 4d,e. The structures of 7d-f
were also analyzed by X-ray diffraction (see 7e in Figure 1). It is
noteworthy that all these molecules exhibit C2-symmetric geometry
as a result of the “antiparallel” arrangement of the carbene ligands,
necessary to avoid severe steric interactions. The 1H and 13C NMR
spectra recorded for the crude products confirmed the absence of
the meso diastereomers that would result from a “parallel”
arrangement of the ImPy ligands in 7.
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The structure of the imidazo[1,5-a]pyridinium salts suggests
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deprotonation at C(1).7 To this aim, salt 10a was reacted with Ag2O
to afford Ag complex 11 in 89% yield (Scheme 2). Transmetalation
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