A short way to switchable carbenes

Article abstract of DOI:10.1002/adsc.201100183

A new, one-step route to N-heterocyclic oxo-carbene complexes (NHOCs), representatives of chemo-switchable NHC complexes, is reported. This simple procedure provides an easy access to gold, palladium and platinum complexes of these ligands. Copyright

Full text of DOI:10.1002/adsc.201100183

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DOI: 10.1002/adsc.201100183
A Short Way to Switchable Carbenes
A. Stephen K. Hashmi,a,* Christian Lothschꢀtz,a Katharina Graf,a Tobias Hꢁffner,a
Andreas Schuster,a and Frank Romingera
a
Organisch-Chemisches Institut, Ruprecht-Karls-Universitꢁt Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg,
Germany
Fax : (+49)-6221-54-4205; e-mail: hashmi@hashmi.de
Received: March 14, 2011; Published online: June 16, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adcs.201100183.
Abstract: A new, one-step route to N-heterocyclic
oxo-carbene complexes (NHOCs), representatives
of chemo-switchable NHC complexes, is reported.
This simple procedure provides an easy access to
gold, palladium and platinum complexes of these li-
gands.
new class of NHCs with switchable electronic proper-
ties have been reported. While Bielawski et al. as well
as the group of Siemeling used NHCs comprising
redox-active moieties, Glorius, Cꢂsar and Lavigne in-
dependently established a ligand system which con-
tained a carbonyl moiety in the backbone.[3] Based on
this structural motif, not only pH-dependent switching
was achieved, but also a simple modification by sub-
sequent enolate chemistry was possible (Scheme 1).
To the best of our knowledge, for these carbonyl-
NHCs so far only complexes of copper, rhodium and
iridium have been reported. While all of the known
reports deal with the classic retrosynthetic cut be-
Keywords: carbene ligands; gold; isonitriles; palla-
dium; platinum; vinylgold species
Regarded as curiosity when reported in 1968,[1] N-het- tween the metal centre and the preformed carbene
erocyclic carbenes (NHCs) have become one of the ligand (Scheme 2, top) and thus rely on a troublesome
most important ligand classes in homogeneous transi- multi-step synthesis of the NHC ligand, we were curi-
tion metal catalysis.[2] Recently, several examples of a ous if the concept of an NHC ligand synthesis directly
on the metal (Scheme 2, bottom) would allow an easy
one-step access to other metals important for cataly-
sis, for example, palladium, platinum or gold. In this
paper we report our new route to transition metal
complexes of this new and exciting type of NHC
ligand.[4]
Based on the linear coordination geometry of the
readily available gold(I) complexes, our first studies
focussed on the synthesis of NHOC-gold(I) com-
pounds. To our delight, preformed isonitrile gold(I)
Scheme 1. Chemo-switchable NHC complex.
complexes smoothly delivered the corresponding
Scheme 2. Different concepts for the access to N-heterocyclic-oxo-carbene complexes (NHOCs).
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Scheme 3. NHOC-Au(I) compounds synthesised.
NHOCs within reasonable reaction times (36 h) and
under very mild reaction conditions.[5] And even a fur-
ther simplification was possible, a one-pot strategy
using the popular (tht)AuCl (tht=tetrahydrothio-
phene),[6] a free isonitrile and an a-amino ester. With
this straight-forward protocol a whole series of car-
bene complexes could be synthesised. As presented in
Scheme 3, we succeeded in the synthesis of a broad
variety of compounds bearing aromatic and aliphatic
residues. The yields were moderate to high. The varia-
bility of the yields cannot be explained by an incom-
plete conversion, but by the work-up procedure. In
some cases it was even possible (e.g., compounds 3
and 7) to purify the precipitate of the product by
simply washing it with pentane. In other cases, the
compounds had to be purified by flash chromatogra-
phy, which resulted in lower yields. In addition to
these examples, by using a cyclic amino ester as pre-
cursor (complex 9), we also succeeded in the synthesis
of a polycyclic NHOC in excellent yield. The constitu-
tion of the resulting NHOC-gold(I) complexes could
unambiguously be proven by the solid state structure
analysis of compound 1 (Figure 1).[7] The competition
between the carbonyl group and the carbene carbon
Figure 1. Bond lengths of the two independent molecules
from the solid state molecular structure of compound
1 (in ꢄ)
atom for the nitrogen lone pair is demonstrated by The largest difference between the two molecules is
two independent molecules in the same unit cell, each the differing amide bond lengths and the resulting
À À
of them resembling more closely to one of the meso- change of the N C N angle.
meric forms. This effect might be caused by the pack-
To explore the scope of this concept for the prepa-
ing and the resulting anisotropy of the single crystal. ration of NHOC complexes, we also used platinum
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A Short Way to Switchable Carbenes
Scheme 4. Formation of Au(I) and Pt(II) complexes.
and palladium isonitrile complexes as precursors
(Scheme 4). As in the case of gold, a simple one-pot
procedure delivered the first examples of the corre-
sponding platinum and palladium NHOC complexes
in good yields. Fortunately, we were also able to grow
crystals suitable for X-ray structure analysis for the
palladium compound (Figure 2).[7] The excess of the
amino ester in this experiment resulted in the forma-
tion of the corresponding trans-amine complex 11b.
The use of stochiometric amounts of the precursors
smoothly led to the desired cis-complex 11a. Com-
pared to gold as central metal, the reaction turned
out to be much slower in the cases of palladium and
platinum (reaction time 14 days at room tempera-
ture). When the reaction was stopped after one day,
we could isolate the non-cyclic compound 11c. This
strongly indicates that the mechanism is composed of
two consecutive reaction steps as depicted in
Scheme 5.
Figure 2. Solid state molecular structures of compounds 11b
(top) and 11c (bottom)
tains one sp2-centre, allowing the formation of the
As demonstrated in the few examples of the pre- stable chair form. However in carbene 14, the six-
ceding publications for other metals, the presence of membered ring contains two sp2-centres, forcing the
the carbonyl moiety in the outer coordination sphere boat form. The gain of aromaticity might overcom-
of the NHOCs allows the switching of the electronic pensate the increased steric strain in the annulated
characteristics. In our first experiments we used the ring. For further variation we synthesised an isoni-
air- and moisture-stable NHOC-Au(I) complex 3 trile-Au(I) organyl 16 according to the procedure de-
(Scheme 6). In doing so, the deprotonation allowed scribed by Hammond et al. Following our synthesis, it
the characterisation of the enolate anion by low tem- was possible to generate an NHOC-Au(I) organyl in
perature NMR. Subsequently, the addition of electro- good yield (Scheme 7).[8] This type of compound is a
philes led to a first repertory of different compounds. part of our current research.
In addition to benzoic acid and silyl derivatives we
The NHOC complexes show catalytic activity, one
also used NVOC chloride (6-nitroveratryloxycarbonyl example is the conversion of 18 to 19. With only
chloride) as electrophile. This special group can be re- 0.1 mol% of catalyst 1 a 98% yield of the phenol 19
moved by irradiation and might allow irreversible in (turnover number TON=980) was isolated.[9] In this
situ switching of the NHOC complex (see Supporting reaction the initial turnover frequency (TOF) is
Information).
Moreover, we succeeded in the formation of a gave a similar yield (97%) but only a TOF of 130 hÀ1.
TBDPS-protected analogue (14) of compound 9 With an N,O ligand on a gold(III) complex a slightly
(Scheme 8). In 9 the fused six-membered ring con- better TON of 1180 has been reported for this reac-
350 hÀ1, the same conversion with the IPrAu+ catalyst
AHCTUNGTRENNUNG
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Scheme 5. Mechanistic proposal for NHOC synthesis.
Scheme 6. Switching of the NHOC-Au(I) complexes to enol derivatives.
Scheme 7. Synthesis of NHOC-Au(I) organyls.
tion,[10] but in this case the TOF was only 120 hÀ1.
This clearly shows the kinetic superiority of the lysts in the cycloisomerisation of the substrate 20 with
NHOC complex 1 in such catalysis reactions. the internal alkyne (Table 1). Usually, these reactions
Next, we investigated the performance of the cata-
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A Short Way to Switchable Carbenes
NHOC complexes in catalysis as well as potential ap-
plications in coordination chemistry and material sci-
ence are part of our ongoing research.
Experimental Section
Scheme 8. Catalytic activity of the activated NHOC gold(I)
complex 1 (the control experiment with AgNTf2 gave no
conversion).
Synthesis NHC-Gold(I) Complexes; General
Procedure
Under an atmosphere of nitrogen (tht)AuCl (1.00 equiva-
lent) was dissolved in absolute DCM (0.10M) at room tem-
perature. The isonitrile (1.05 equivalents) was added and the
solution was stirred for 5 min. After this, the amine
(1.50 equivalents) was added and stirring was continued for
36 h. The solvent was removed under reduced pressure and
the resulting crude product was washed with cold pentane
[five times, 2.00 mL/50.0 mmol (tht)AuCl] (method A). The
product was dried under reduced pressure. Alternatively,
the compounds can be purified by column chromatography
using DCM as eluent on basic alumina (method B).
Table 1. Catalytic conversion of internal alkynes.
Entry Catalyst
Products
Chloro[1-cyclohexyl-3-(2,6-diisopropylphenyl)imidazolin-
4-on-2-ylidene]gold(I) (1): Colourless solid, yield: 199mg
(356 mmol, 76%) (method A); H NMR (500 MHz, CDCl3/
1
2
3
4
5 mol% IPrAuCl/5 mol%
AgOTs
5 mol% 1/5 mol% AgOTs
21 (41%), 22
(37%)
21 (44%), 22
(35%)
21 (49%), 22
(32%)
21 (43%), 22
(37%)
1
C6D6, 4/1): d=1.21 (d, J=6.9 Hz, 6H, CH3), 1.37 (d, J=
6.9 Hz, 6H, CH3), 1.56 (m, 4H, CH2), 1.81 (m, 1H, CH2),
1.96 (m, 2H, CH2), 2.10 (m, 2H, CH2), 2.64 (m, J=6.9 Hz,
1H, CH), 4.08 (s, 2H, CH2), 4.58 (m, 1H, CH), 7.3 (d, J=
7.8 Hz, 2H, ArH), 7.5 (t, J=7.8 Hz, 1H, ArH); 13C NMR
(125 MHz, CDCl3/C6D6, 4/1): d=24.25 (2C), 24.29 (2C),
24.97, 25.10 (2C), 29.50 (2C), 31.99 (2C), 48.59, 63.29,
124.73 (2C), 128.29, 129.24, 131.22 (2C), 171.84, 201.85; IR
5 mol% 5/5 mol% AgOTs
5 mol% 7/5 mol% AgOTs
˜
(KBr): n=2962, 2932, 2862, 1768, 1524, 1467, 1453, 1384,
1366, 1338, 1300, 1261, 1221, 1168, 1098, 1056, 1027, 803,
681 cmÀ1
;
HR-MS (FAB+): m/z=523.2019, calcd. for
do not proceed efficiently, which allowed the isolation
of a vinylgold intermediate.[11] Again, in these reac-
tions both IPrAu+ and the activated NHOC com-
plexes 1, 5 and 7 gave a complete conversion and sim-
ilar yields of the two reaction poducts. Once more,
the major difference was the rate of the reaction, 1, 5
and 7 were 3.5–4 times faster, when switching to
DCM as solvent, IPrAu+ failed to convert 20, while
the NHOCs still stayed active and showed a shift in
selectivity, now the oxazine 22 became the major
product (switching from a ratio 21:22ꢀ1:1 in THF to
about 1:3 in DCM).
In addition to these initial catalytic results, one
must keep in mind that NHCs potentially can be
transmetallated from gold to other metals, too.[11]
In this communication we have reported an easy
one-step procedure for the synthesis of a broad varie-
ty of interesting NHOC complexes. We were able to
prepare the corresponding compounds of Au(I),
Pd(II) and Pt(II). In case of NHOC-Au(I) compounds
we even succeeded in the formation of the electroni-
cally “switched” analogues. The NHOC-Au(I) com-
plexes are active in the gold-catalysed phenol synthe-
sis and the gold-catalysed cycloisomerisation of prop-
argyl amides to alkylideneoxazolines and oxazines.
C21H30O2N [MÀClÀ]+: 523.2024; anal. calcd. for
C21H30ClN2OAu·0.18CH2Cl2: C 40.30, H 5.33, N 4.88; found:
C 40.30; H 5.46, N 4.77. This reaction has also been carried
out on a 1.00-mmol scale with comparable yield.
Chloro(1-cyclooctyl-3-(2,6-diisopropylphenyl)imidazolin-
4-on-2-ylidene)gold(I) (2): Colourless solid, yield: 120mg
1
(197 mmol, 42%) (method B); H NMR (300 MHz, CD2Cl2):
d=1.06 (d, J=6.9 Hz, 6H, CH3), 1.22 (d, J=6.9 Hz, 6H,
CH3), 1.43–1.95 (m, 14H, CH2), 2.54 (m, J=6.9 Hz, 2H,
CH), 4.11 (s, 2H, CH2), 4.69 (m, 1H, CH), 7.22 (d, J=
7.8 Hz, 2H, ArH), 7.44 (t, J=7.8 Hz, 1H, ArH); 13C NMR
(75 MHz, CD2Cl2): d=24.17 (2C), 24.21 (2C), 24.63 (2C),
26.16, 26.84 (2C), 29.60 (2C), 32.66 (2C), 49.49, 64.98,
124.86 (2C), 129.78, 131.25, 146.87 (2C), 172.38, 201.03; IR
˜
(KBr): n=2962, 2926, 2867, 1768, 1521, 1468, 1457, 1447,
1384, 1373, 1363, 1340, 1302, 1248, 1213, 1155, 805 cmÀ1
;
HR-MS (FAB+): m/z=551.2352, calcd. for C23H34ON2Au
[MÀClÀ]+: 551.2337.
Formation of 11a
Under an atmosphere of nitrogen the Pd(II) isonitrile com-
plex (100 mg, 181 mmol) was dissolved in absolute THF
(8.00 mL). To this solution the amine (37.2 mg, 217.2 mmol,
1.2 equivalents) was added and the mixture was stirred for
21 days at room temperature. After this period, half of the
Further investigation of the application of the new solvent was removed under reduced pressure and pentane
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(10.0 mL) was added in order to precipitate the product.
The product was filtered off and dried under reduced pres-
sure to afford a pink solid; yield: 83.9 mg (121 mmol, 67%);
1H NMR (500 MHz, CD2Cl2): d=0.88 (d, J=6.7 Hz, 3H,
CH3), 0.91 (d, J=6.7 Hz, 3H, CH3), 0.97 (d, J=6.7 Hz, 3H,
CH3), 1.13 (d, J=6.8 Hz, 6H, CH3), 1.15 (d, J=6.8 Hz, 6H,
CH3), 1.29 (d, J=6.5 Hz, 3H, CH3), 1.43–1.75 (m, 6H, CH2),
1.91 (m, 3H, CH2), 2.51 (m, 1H, CH), 2.98 (m, J=6.7 Hz,
1H, CH), 3.09 (m, J=6.8 Hz, 2H, CH), 4.27 (d, J=21.0 Hz,
1H, CH2), 4.34 (d, J=21.0 Hz, 1H, CH2), 5.05 (m, 1H, CH),
7.16 (m, 3H, ArH), 7.36 (m, 2H, ArH), 7.48 (t, J=7.8 Hz,
1H, ArH); 13C NMR (75 MHz, CD2Cl2): d=22.28, 23.06
(2C), 23.39 (2C), 23.72, 25.28, 25.30, 25.57, 25.75, 25.80,
29.63, 30.16 (2C), 30.25, 31.31, 32.25, 50.02, 64.13, 124.31,
124.43 (2C), 125.89 (2C), 129.22, 131.63, 131.75, 145.92,
146.52 (2C), 149.04, 171.25, 198.35 (isonitrile carbon atom
1970, 92, 2555–2557; b) A. L. Balch, J. E. Parks, J. Am.
Chem. Soc. 1974, 96, 4114–4121; a recent report on the
intramolecular cyclisation of isocyanoacetate does need
a separate second alkylation step with another reagent
to form a carbene ligand and also did not aim at cataly-
sis either: c) S. Schrçlkamp, A. Vçlkl, T. Lꢀgger, F. E.
Hahn, W. Beck, W. P. Fehlhammer, Z. Anorg. Allg.
Chem. 2008, 634, 2940–2947; as the preceeding refer-
ence, other examples of known template synthesis at
the metal centre using isonitriles are based on entirely
different disconnections of the NHC framework and in
addition do not lead to the NHCs with oxo groups in
the backbone: d) F. E. Hahn, V. Langenhahn, N. Meier,
T. Lꢀgger, W. P. Fehlhammer, Chem. Eur. J. 2003, 9,
704–712; e) F. E. Hahn, C. G. Plumed, M. Mꢀnder, T.
Lꢀgger, Chem. Eur. J. 2004, 10, 6285–6293; f) for a
review also covering such syntheses, see: F. E. Hahn,
M. C. Jahnke, Angew. Chem. 2008, 120, 3166–3216;
Angew. Chem. Int. Ed. 2008, 47, 3122–3172.
˜
was not observed); IR (KBr): n=2965, 2933, 2866, 2186,
1756, 1635, 1590, 1533, 1465, 1386, 1363, 1349, 1296, 1271,
1212, 1182, 1007, 800, 750 cmÀ1; HR-MS (FAB+): m/z=
654.2444, calcd. for C34H47ON3ClPd [MÀClÀ]+: 654.2442.
[5] Selective conversions are also possible at 808C, but we
preferred the mild conditions at room temperature.
The addition of molecular sieves to sequester the meth-
anol formed during the reaction does not show any
beneficial effect, which is understandable for two rea-
sons: (i) kinetics: the rate-limiting step is the addition
of the amine to the coordinated isonitrile, and metha-
nol is not involved in this first step of the reaction but
in the second, subsequent step; (ii) thermodynamics:
the amide formation from an ester is strongly exother-
mic, and since the amide formation is intramolecular,
the entropy is also clearly in favour for this process
even in the absence of molecular sieves.
[6] While (Me2S)AuCl is commercially available, (tht)AuCl
is easy to prepare and sets free the less smelly thioeth-
er. We tested two representative reactions also with
(Me2S)AuCl and as expected obtained the same results.
[7] CCDC 818376 (1), CCDC 818377 (11b) and CCDC
818378 (11c) contain the supplementary crystallograph-
ic 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.
Acknowledgements
C. Lothschꢀtz is thankful for financial support by the Stud-
ienstiftung des deutschen Volkes e.V.
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