Synthesis and reactivity of metal carbene complexes with heterobiaryl spacer substituents

Article abstract of DOI:10.1039/b811762d

Mono- and binuclear Fischer carbene complexes, [M(CO)₅{C(OR)Ar- ArX}], X = H, {C(OR)M′(CO)₅}; M, M′ = W or Cr; R = Me, Et or (CH₂)₄OMe; Ar = thiophene, N-methylpyrrole or furan units 1-20, were synthesized. For

Full text of DOI:10.1039/b811762d

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Synthesis and reactivity of metal carbene complexes with heterobiaryl
spacer substituents†
Simon Lotz,*a Chantelle Crause,a Andrew J. Olivier,a David C. Liles,a Helmar Go¨rls,b Marile´ Landmana and
Daniela I. Bezuidenhouta
Received 22nd July 2008, Accepted 10th October 2008
First published as an Advance Article on the web 24th November 2008
DOI: 10.1039/b811762d
Mono- and binuclear Fischer carbene complexes, [M(CO)5{C(OR)Ar-ArX}], X = H,
{C(OR)M¢(CO)5}; M, M¢ = W or Cr; R = Me, Et or (CH2)4OMe; Ar = thiophene, N-methylpyrrole or
furan units 1–20, were synthesized. For this purpose, mono-, bi- or stepwise lithiated bithiophene,
N,N¢-dimethylbipyrrole, thienylfuran and N-methyl(thienyl)pyrrole were reacted with chromium and
tungsten hexacarbonyl precursors. Dilithiation in the 2- and 9-positions of N-methyl(thienyl)pyrrole
could not be achieved. Alkylation of acyl metallates with triethyloxonium tetrafluoroborate or methyl
trifluoromethanesulfonate in THF afforded not only the expected carbene complexes with ethoxy or
methoxy substituents, but in the case of bithiophene with methyl trifluoromethanesulfonate, carbene
complexes with alkoxy substituents incorporating a ring-opened tetrahydrofuran moiety. X-Ray
crystallographic structure determinations were performed on [W(CO)5{C(OMe)(thienylfuran)}] (14),
[W(CO)5{C(OMe)(N-methylthienylpyrrole)}] (20) and [{W(CO)5}2{m-C(OEt)(N,N¢-
dimethylbipyrrolylC(OEt)}] (12) to assess the role of the heterobiaryl substituent on the structural
features of the carbene ligand in the complexes. Complexes [{Cr(CO)5}2{m-C(OMe)bithienylC(OEt)}]
(3), [(CO)5Cr{m-C(OMe)bithienylC(OMe)}W(CO)5] (5) and [{Cr(CO)5}2{m-C(OMe)thienylfuranC-
(OMe)}] (15) were reacted with 3-hexyne to study their behaviour in benzannulation reactions. The
major products generated by the biscarbene complexes were regio-selectively determined by the nature
of the metal site and that of the heteroatom in the arene rings. The monocarbene complexes
[Cr(CO)5{C(OMe)thienylfuran] (13) and [Cr(CO)5{C(OEt)(N-methylthienylpyrrole)}] (19) were
refluxed in THF for 2 hours in the presence of [Pd(PPh4)4] to afforded the carbene–carbene coupled
olefinic products and small amounts of the corresponding 2-ethyl(biheteroaryl)acetate. By contrast, the
biscarbene complex of thienylfuran (15), afforded only the 2,9-diester of thienylfuran.
choice in our laboratories when starting from monoheteroaryl
precursors and adaptations were made from the published
methods.10
Introduction
Heteroaromatic five membered rings, linked at the a-carbon
atoms, form p-conjugated chain structures and can facilitate
charge transfer or electron delocalization from one end of the
molecule through the backbone to the opposite end.1 For effective
p–conjugation coplanarity of the rings must be retained. In view
of the many applications of heterobiaryls, a number of catalytic
methods have been developed to prepare biaryl heterocycles of
thiophene, furan and pyrrole from monoheteroaryl precursors
and invariably proceed using either nickel or palladium catalysts.2
Some of the most commonly used catalytic methods are the
Kharasch,3 Negishi,4 Stille5 and Suzuki6 coupling reactions.
These catalytic routes enable the facile preparation of both
symmetrical and asymmetrical heterobiaryls in cross-coupling
reactions. Although some non-catalytic methods have also been
used (photochemical,7 direct coupling,8 cyclization,9 etc. reac-
tions) the catalytic cross-coupling methodology is the method of
The attachment of two different transition metal fragments
at the termini of a linear, planar and conjugated heteroarene
spacer will create two different electronic and chemical poles
in the molecule. Maiorana and co–workers11 prepared the first
Fischer mixed-metal biscarbene complex of bithiophene to study
potential non-linear optical properties of such complexes. Progress
in this area of research has been hampered by limited methods of
synthesis. Phenyl, acetylene and ethene units are more commonly
found in conjugated bridging ligands, but are often not very stable
compared to heteraromatic moieties.12
Heteroarene substrates are readily deprotonated at the a–
position, using the strong base n-BuLi.13 The resulting heteroaryl
nucleophiles can attack carbonyl ligands of transition metal
carbonyl precursors and after subsequent alkylation afford Fischer
metal carbene complexes.14 It is also possible to prepare biscarbene
complexes with metal fragments on both sides of the heteroarene
spacer from bimetallated substrates, creating an electronic path-
way for potential metal–metal communication.15 Carbon atoms
in Fischer carbene complexes are highly reactive electrophilic
centres which are stabilized by electron donating substituents.16
The transfer of electron density from an electron rich heteroarene
aDepartment of Chemistry, University of Pretoria, Pretoria 0002, South
Africa. E-mail: simon.lotz@up.ac.za; Fax: +27 (0) 12 420 4687
bFriedrich-Schiller-Universita¨t, Institut fu¨r Anorganische und Analytische
Chemie, Lessingstrasse 8, Jena 07743, Germany
† CCDC reference numbers 686736–686738. For crystallographic data in
CIF or other electronic format see DOI: 10.1039/b811762d
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substituent to the carbene carbon atom can contribute to the
stabilization of the carbene ligand.17
zinc chloride and 2-bromothiophene in the presence of
the palladium(II)chloride-1,1¢-bis(diphenylphosphino)ferrocene
catalyst.21 This reaction was not optimized and since significant
quantities of unreacted 2-bromothiophene were detected the
yield could be improved by employing longer reaction times.
Wynberg and co-workers22 reported that thienylfuran derivatives
are sensitive to light, heat and moisture and observed darkening
of the compounds after a few days even while stored at -20 ◦C
under nitrogen and in the dark.
Since the properties of condensed ring heteroarene carbene
complexes have been explored in our laboratories,18 a study of
the analogous 2,2¢-heterobiaryl substrates was undertaken.
A systematic comparison of the four different biaryl heterocy-
cles S1, S2, S3 and S4, shown in Fig. 1, on the conditions of
metallation as well as application in Fischer carbene synthesis
was investigated. The atom numbering shown in Fig. 1 is
unconventional, but represents the labels used in this study for
the reported complexes. The method used for carbene synthesis
was determined by the deprotonation step of the substrates. To
facilitate 2- or 2,9-deprotonation of the pyrrole substrates it was
required to replace the hydrogen atom attached to the nitrogen of
the ring with a methyl group.
Metallation studies
Monometallation studies of heterocyclic substrates have provided
a general rule of oxygen and sulfur > nitrogen (N-substituted
nitrogen arene compounds). Thus lithiation a to sulfur is favoured
and occurs at low temperatures in THF, whereas more stringent
conditions are needed to deprotonate the position a to nitrogen
in a N-substituted pyrrole moiety. It is known that in competitive
reactions between furan and thiophene for an insufficient quantity
of n-BuLi, furan reacts more rapidly in hexane than thiophene.23
On the other hand, thiophene reacts more rapidly than furan
under reaction conditions that favour the ionisation of the C–Li
bonds (THF, etc.).24 However, in both cases the lithiation occurs in
the a-position of such hetero◦cycles. Bithiophene (S1) was readily
dimetallated in THF at -20 C with two equivalents of n-BuLi.
This becomes more difficult for the deprotonation of S2, because
n-BuLi attacks THF at temperatures above 0 ◦C. Hence hexane is
the solvent of choice to access higher temperatures for lithiation
and TMEDA is employed as co-catalyst for the 2,9-dilithiation of
N,N¢-dimethylbipyrrole. S3 was mono-lithiated under conditions
that would favour deprotonation, a to the sulfur atom (the first
lithiation was achieved at -20 ◦C) and deprotonated with a second
equivalent of n-BuLi on the furan ring, again a to the oxygen atom,
to afford the 2,9-dilithiated thienylfuran precursor. S4 is readily
monolithiated in THF at low temperatures on the thiophene ring,
but higher temperatures required for deprotonating on the N-
methylpyrrole ring lead to decomposition and inter-ring bond
cleaving.
Fig. 1 Linear biaryl heterocycles (S1–S4).
In this article the synthesis of mononuclear carbene complexes
with electron rich heteroaromatic substituents and binuclear
biscarbene complexes with bridging heteroarene spacer units is
reported. A synthetic method was devised to synthesize biscarbene
complexes containing different metal fragments at the termini
of the conjugated bridging heteroarene ligand. The structural
features of complexes were studied in the solid state by crystal
structure determinations and in solution by NMR spectroscopy.
The role of the heteroatoms in the rings to affect electron
delocalization and influence chemical transformations in carbene
complexes was investigated.
Results and discussion
Synthesis of carbene complexes
Synthesis of heterobiaryl precursors (S1–S4)
The monocarbene and dimetal biscarbene complexes (Table 1,
list of complexes) were prepared according to Scheme 1. The
monocarbene complexes can be synthesized in high yields (above
60%) after monolithiation of the substrates. However, in this study
they were isolated as by-products (ca. 20%) from the reaction
mixture of the dilithiated substrates and metal carbonyls. Their
formation can be ascribed to incomplete dimetallation of the
heterobiaryl precursors. In solution, the biscarbene complexes
decompose over time but can be stored for longer periods under
Bithiophene (S1) is commercially available. A high yield synthesis
(>90%) from thiophene, BuLi, ZnI2, NCS and Pd(PPh3)4 as the
catalyst has been reported recently for bithiophene.19
2,2¢-N,N¢-Dimethylbipyrrole (S2) was synthesized by an oxida-
tive coupling reaction between 2-lithio-N-methylpyrrole and N-
methylpyrrole in the presence of anhydrous nickel(II) chloride.
2,2¢-Thienylfuran (S3) was prepared from 2-tributylstannyl-
furan and 2-bromothiophene via the Stille reaction. The tin precur-
sor was prepared quantitatively from 2-lithiofuran by following the
literature procedure.20 The Pd(PPh3)4-catalysed reaction between
the tin precursor and a 50% molar excess of 2-bromothiophene
proceeded smoothly to afford S3 as a rose coloured oil in a 67%
◦
isolated yield. This compound was stored below 0 C and under
an inert atmosphere since it was found to gradually darken over
time at room temperature due to decomposition.
The Negishi cross-coupling reaction was employed to prepare
N-methyl-2-(2¢-thienyl)pyrrole (S4) from 2-(N-methylpyrrolyl)-
Scheme 1 General procedure for the synthesis of the carbene complexes
1–20.
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Table 1 List of complexes
X = S, Y = S
n = 0
n = 1
M = Cr
M = W
M = Cr
M = W
M = Cr
M = Cr
M = W
M = W
M = Cr
M = W
M = Cr
M = W
M = Cr
M = W
M = Cr
M = W
M = Cr
M = W
M = Cr
M = W
R = Me
R = Me
R = Me
R = Me
R = Me
R = Me
R = Me
R = (CH2)4OMe
R = Et
1
2
3
4
5
M¢ = Cr
M¢ = W
M¢ = W
M¢ = Cr
M¢ = W
M¢ = W
R¢ = Me
R¢ = Me
R¢ = Me
R¢ = (CH2)4OMe
R¢ = (CH2)4OMe
R¢ = (CH2)4OMe
6
7
8
X = NMe, Y = NMe
X = S, Y = O
n = 0
n = 1
n = 0
n = 1
9
R = Et
10
11
12
13
14
15
16
17
18
19
20
M¢ = Cr
M¢ = W
R = Et
R¢ = Et
R¢ = Et
R = Et
R = Me
R = Me
R = Me
R = Me
R = Me
R = Me
R = Et
M¢ = Cr
M¢ = W
M¢ = W
M¢ = Cr
R¢ = Me
R¢ = Me
R¢ = Me
R¢ = Me
X = S, Y = NMe
n = 0
R = Et
inert atmosphere in the solid state, whereas the monocarbene
complexes are stable.
Three procedures, taking into account the best conditions for
the dimetallation of S1–S4 as well as the most effective way to
achieve a reaction with the metal hexacarbonyl, were used for the
synthesis of the carbene complexes.
alkylation in dichloromethane. Surprisingly, the butoxy(methoxy)
carbene complexes 7 and 8 were formed again, albeit in a lower
yield (10% and 7% respectively). This was also observed during
the synthesis of the chromium derivatives with 10% of 6 isolated
after alkylation in dichloromethane. The chromium analogue of
8 was not isolated and characterised since sufficient quantities
could not be removed from the silica gel column. These results
indicated that the incorporated THF might be associated with an
intermediate acyl metallate or be trapped in the residue and is thus
not eliminated during the removal of the solvent under reduced
pressure.
Method 1. Dilithiated bithiophene was reacted with the metal
hexacarbonyl at low temperature and alkylation of the interme-
diated products with methyl trifluoromethanesulfonate affording
the mono- and biscarbene complexes (1–4) as well as complexes
where alkylation proceeded via ring opening of tetrahydrofuran
(6–8). Do¨tz and co-workers25 were the first to observe an opening
of the THF ring during alkylation of Fischer carbene complexes
with magic methyl. Raubenheimer and co-workers reported the
formation of similar compounds during the alkylation of carbene
complexes containing an azolyl organic substituent.26 A similar
reaction leading to THF ring opening has been observed in
our laboratories with p-coordinated thienyl chromium tricarbonyl
substituents.27 The THF insertion is initiated by a nucleophilic
attack of the metal acyllate on the a-carbon of the THF leading
to ring cleaving and the formation of the butoxy(methoxy) carbene
complexes (Scheme 2).
Method 2. In the second procedure, used for N,N¢-
dimethylbipyrrole complexes, a mixture of lithiated and dilithiated
N,N¢-dimethylbipyrrole (S2) was obtained from n-BuLi/TMEDA
in hexane at elevated temperatures.28 This mixture was added at
low temperature to a THF solution containing the metal car-
bonyl. Alkylation with triethyloxonium tetrafluoroborate afforded
monocarbene complexes (9, 10) inyields of 20–30% andbiscarbene
complexes (11, 12) in yields of 35–45%. When applied to S4, no
dinuclear biscarbene complexes formed and only monocarbene
complexes were found, on the a-position of the thiophene moiety.
Method 3. This route comprised a modified version of a
method used by Aoki involving a stepwise lithiation procedure and
anionic protection of the formed monoacyl metallate (Scheme 3).29
This method, which worked well, was previously used in our labo-
ratories to prepare the mixed metal (Cr,W) biscarbene complex of
Scheme 2 Ring-opening of THF during alkylation of 6–8.
The alkylation of the tungsten derivatives was carried out in
two ways. In the first attempt THF was used as solvent for the
alkylation and large quantities of 7 (28%) and 8 (17%) were
isolated. These complexes displayed a high retention on a silica
gel column which complicated purification and led to significant
losses, of 8 especially, where two equivalents of THF were incor-
porated. The synthesis was repeated by first removing all solvents
in vacuo followed by washing the residue with aliquots of hexane.
Hence the remaining THF was removed before carrying out the
Scheme 3 Method of anionic protection during the synthesis of mixed
metal biscarbene complexes.
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furan.30 In this particular study, the method was applied to prepare
5, 17 and 18 and also to increase yields of homonuclear biscarbene
complexes 3, 4, 6, 7, 8, 15 and 16. In the case of bithiophene, S1
was monolithiated and reacted with Cr(CO)6 or W(CO)6. The
reaction mixture was cooled to -70 ◦C, the proton of the acyl
metallate was removed from position 9 by freshly prepared LDA
and the mixture reacted with a second metal carbonyl precursor.
For 5, after alkylation with methyl trifluoromethanesulfonate,
the isolated yield of the Cr,W-bithiophene biscarbene complex
was low compared to that reported for the furan analogue (12%
versus 47%). Similar quantities of the corresponding monocarbene
complexes of bithienyl, butyl (from n-BuLi) and diisopropylamide
(from LDA) substituents were also isolated from the reaction
mixture.
no attempt has been made to isolate intermediates or minor
organic products. The reactions of the biscarbene metal complexes
with 3-hexyne were carried out in toluene at 80 C with a metal
concentration of 0.1 mol dm-3 and 4 molar equivalents of alkyne.
Higher concentrations of the metal complexes were not possible
because of their poor solubility in toluene. Reactions were allowed
to proceed for 24 h after which the major coloured product
was isolated with column chromatography and characterised by
NMR and infrared spectroscopy, and mass spectrometry. The
composition of the products is shown in Scheme 4.
◦
S3 was mono-lithiated, treated with M(CO)6 to form the
acyl metallate and subsequently a second proton was abstracted
with LDA. The resulting dianion was reacted with a second
equivalent of M(CO)6 followed by alkylation with methyl tri-
fluoromethanesulfonate in dichloromethane. The monocarbene
complexes 13 and 14 were the main products isolated together with
the homometallic biscarbene complexes 15 and 16. By-products
that formed but were not purified, include butyl carbene complexes
as well as carbene complexes with incorporated THF in the alkoxy
substituent.
Scheme
complexes.
4
Regioselective benzannulation reactions of biscarbene
Because of the higher temperatures required to deprotonate S2,
this method was not used during the synthesis of 9–12.
Only monocarbene complexes could be isolated using method
1 for S4 (19, 20) as excess n-BuLi and harsher reaction conditions
lead to pyrrole–thiophene bond cleavage resulting from the
nucleophilic addition of butyl on the thiophene side of the inter-
ring bond.
In synthesizing mixed metal biscarbene complexes 17 and
18, the composition of the final biscarbene complex was deter-
mined by the order of metal hexacarbonyl precursor addition.
Finally, the sensitivity and selectivity of a specific metal site
towards carbon-carbon coupling reactions were tested for selected
examples.
The modified bithiophene monocarbene complex 21 was the
major product from the reaction of 3 with 3-hexyne. For the mixed
Cr,W-binuclear biscarbene complex 5 the formation of 22 was
not unexpected since it is generally known that for mononuclear
carbene complexes of chromium, the carbonyl ligands are more
labile compared to analogous tungsten carbonyl complexes.
This will favour the carbonyl insertion step in the formation
of the benzothiophene unit during the reaction and make the
chromium carbene site the preferred centre for the benzannulation
reaction. This result demonstrated that regioselective discrim-
ination between the two different metal carbene sites (Cr,W)
is possible for this particular reaction, as well as simultaneous
protection of a second metal carbene centre. In addition to
this, no other simple route is known to exist to synthesize 22,
the tungsten monocarbene analogue to the modified chromium
carbene complex 21. The formation of 23 from 15 illustrates the
role of the heteroatom in the arene rings (thiophene vs. furan)
to direct the reaction and determine the composition of the
product.
Benzannulation reactions
The selectivity of a specific metal site and/or the role of
the heteroatom in the heteroarene ring was tested by reacting
the appropriate biscarbene complex with 3-hexyne in the well
known Do¨tz reaction for Fischer carbene complexes.31 Het-
eroaryl monocarbene complexes with furyl, thienyl and pyrrolyl
substituents also undergo Do¨tz reactions.16d,32 Wulff and co-
workers33 optimised the reaction conditions for monocarbene
complexes with phenyl substituents to afford naphthol products.
The chromium complexes displayed the highest selectivity to
afford products where the insertion of a carbonyl leads to
benzannulation products. Optimal conditions are found with
higher metal concentrations and with less polar or coordinating
solvents and were applied in the reactions of complexes 3, 5
and 15 with 3-hexyne. Very few accounts of the reactions of
biscarbene complexes with alkynes have been reported34 and as
far as we are aware the only other example starting from mixed
metal biscarbene complexes with heteroarene substituents was
reported earlier from our laboratories.30 The present study deals
only with the major products formed during the reactions and
Carbene coupling reactions
Early work on the reactivity of Fischer carbene complexes focused
on the ability of these to act as stable carbene sources. Amongst
others, it was found that the carbene ligand undergoes thermal
dimerization,35 yields esters through oxidative decomposition36
and form cyclopropanes through carbene transfer to activated
alkenes.37 In a second example the objective was to study carbene–
carbene coupling reactions in the presence of a palladium cata-
lyst. Sierra and co-workers38 have demonstrated that palladium
catalysts can effectively facilitate the carbene–carbene coupling of
monocarbene complexes. The product (Fig. 2) is representative
of the coupling of two dithienothiophene carbene ligands and
represents a situation whereby a growing p-conjugated chain
700 | Dalton Trans., 2009, 697–710
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