Bond activation with an apparently benign ethynyl dithiocarbamate Ar-C≡C-S-C(S)NR2

Article abstract of DOI:10.1002/anie.201104303

The hedgehog molecule: A simple ethynyl dithiocarbamate [Ar-C≡C-S-C(S)NR₂] is able to cleave a broad range of enthalpically strong σ bonds and to activate carbon dioxide and elemental sulfur (see picture). Depending on the substrate, the bond activation process involves either the existence of an equilibrium with the nonobservable mesoionic carbene isomer or the cooperation of the nucleophilic carbon-carbon triple bond and the electrophilic CS carbon atom. Copyright

Full text of DOI:10.1002/anie.201104303

DOI: 10.1002/anie.201104303
Bond Activation
Bond Activation with an Apparently Benign Ethynyl Dithiocarbamate
À ꢀ À À
Ar C C S C(S)NR2**
Gaꢀl Ung, Guido D. Frey, Wolfgang W. Schoeller, and Guy Bertrand*
Strong bond splitting is the key step in most catalytic chemical
transformations. For many years, it has been a task performed
quasi-exclusively by transition-metal complexes, and it is of
paramount importance to find alternatives that are less costly
and more environmentally friendly. The activation of a strong
bond requires that the pair of bonding electrons is perturbed
in some way so as to form a chemically active species. For
transition-metal complexes the bond splitting results from the
primary interaction between a vacant orbital at the metal and
a bonding orbital of the substrate, with concomitant back-
donation from a filled d orbital at the metal to an anti-
bonding orbital of the bound substrate.[1] Recent works have
Scheme 1. Dithiolium salt 2 is the conjugate acid of MIC A. The
formation of transition-metal complexes 3 shows that ethynyl dithio-
shown that besides transition metals, other reactive chemical
species are able to split enthalpically strong bonds, using
carbamate 1 behaves as a ligand equivalent of MIC A. Tipp=2,4,6-
various modes of activation.[2] The so-called frustrated Lewis
triisopropylphenyl, NR2 =piperidinyl, Tf=trifluoromethanesulfonyl,
[Mp]: [AuCl(tht)], [{PdCl(allyl)}2], [{RuCl2(p-cym)}2], and [{RhCl(cod)}2]
pairs (FLPs)[3] always involve, with one exception,[4] strongly
acidic polyfluorinated boranes or alanes, in combination with
rather weak bases; therefore the activation of the substrates is
electrophilic as for transition metals. In contrast, singlet
carbenes[5] and heavier analogues[6] are strongly basic, and
consequently act as nucleophiles towards the substrates.[7]
Here we report that an apparently benign ethynyl dithiocar-
bamate is able to activate a variety of substrates, using either
the existence of an equilibrium with its mesoionic carbene
(MIC) isomer, or the cooperative effect of two carbon centers.
We recently showed that trifluoromethanesulfonic acid
and a variety of transition-metal complexes induce the ring
closure of ethynyl dithiocarbamate 1, affording the dithiolium
salt 2 and transition-metal complexes 3, respectively.[8,9]
These compounds can be viewed as the conjugate acid and
metal complexes, respectively, of the 1,3-dithiol-5-ylidene A,
a compound belonging to the family of mesoionic car-
benes,[10,11] for which two types of stable derivatives (B[12]
and C[13]) are known (Scheme 1).
where tht=tetrahydrothiophene, p-cym=p-cymene, and cod=1,5-
cyclooctadiene, and [M]: AuCl, PdCl(allyl), RuCl2(p-cym), and RhCl-
(cod).
react with 1 at room temperature giving the corresponding
dithiolium salts 4 and 5, which were isolated in 95 and 92%
yield, respectively (Scheme 2). Decreasing the Lewis acidity
of the substrate, pinacolborane was tested and, at room
These results prompted us to study the extent of the
electrophile-induced ring closing process of ethynyl dithio-
carbamate. Bromine and trifluoroborane instantaneously
[*] G. Ung, Dr. G. D. Frey, Prof. W. W. Schoeller, Prof. G. Bertrand
UCR-CNRS Joint Research Chemistry Laboratory (UMI 2957)
Department of Chemistry, University of California Riverside
Riverside, CA 92521-0403 (USA)
E-mail: guy.bertrand@ucr.edu
Homepage: http://research.chem.ucr.edu/groups/bertrand/
guybertrandwebpage/
[**] Financial support from the NSF (CHE-01112133) is gratefully
acknowledged. We thank B. Donnadieu for his assistance with the X-
ray diffraction studies and Minako Kinjo for designing the cover
illustration.
Scheme 2. Bromine and trifluoroborane induce the ring closing of 1,
whereas for pinacolborane (pinB-H), arylthiol, and even methanol, the
cyclization process is accompanied by the splitting of the heteroatom–
hydrogen bond.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201104303.
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ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
9923

Communications
temperature, it does not only induce the cyclization
À
of 1, but a B H bond cleavage also occurs. The
formation of adduct 7 (94% yield) pointed towards
the electrophilic character of the 2 position of the
putative, first formed, dithiolium 6. To evaluate the
scope of this s–s bond cleavage, we then reacted 1
with the weakly Brønsted acidic 2,6-dimethylthio-
phenol, and observed the clean formation of adduct 8
(94% yield). Further decreasing the acidity of the
substrate, methanol was added to ethynyl dithiocar-
bamate 1, and adduct 9 was quantitatively formed
after 5 min at room temperature. The same com-
pound 9 was also readily obtained in 97% yield by
addition of sodium methoxide to dithiolium trifluor-
omethanesulfonate 2.
It is difficult to believe that methanol is acidic
enough to protonate the carbon–carbon triple bond
of 1, but mesoionic carbenes are strongly basic.
Therefore, we envisaged the existence of an equilib-
rium between the ethynyl dithiocarbamate 1 and its
MIC isomer A. Calculations at the RI-BP86/TZVPP
level of theory[14] predict that A is 8.3 kcalmolÀ1
higher in energy than its acyclic form 1, with a
small energy barrier (0.8 kcalmolÀ1) for the ring-
opening process. To test experimentally the possible
existence of such equilibrium, we first reacted 1 with
Scheme 4. The reactivity of 1 does not parallel the acidity of the substrates,
indicating the key role played by the heteroatom lone pair of the substrate. The
À
N H bond cleavage of methyl hydrazine occurs at the more basic nitrogen.
À
Bond activation by 1 is not limited to X H bonds, as shown by the cleavage of
diphenyldisulfide.
carbon dioxide and elemental sulfur, which are known to
readily react with singlet carbenes[15] and MICs,[12] and very
unlikely to interact with the carbon–carbon triple bond of 1,
at least at room temperature.[16] After 30 min, the corre-
sponding MIC adducts 10 and 11 were isolated in 98 and 97%
yield, respectively (Scheme 3), and fully characterized by
single-crystal X-ray diffraction studies (see the Supporting
Information).
not electrophilic enough to react with the carbon–carbon
triple bond of 1, or the carbene center of MIC A, there is a
collaborative effect between the nucleophilic and electro-
philic centers of 1 as schematically represented by I. Indeed,
we found that N-(2,6-diisopropylphenyl)-N-methylamine,
which is obviously more acidic than diethylamine but more
hindered, does not react with 1, suggesting that a heteroatom
lone pair of the substrate has to interact with the electrophilic
center of 1 to allow for the reaction. A confirmation of this
hypothesis was brought by the reaction of 1 with methyl
hydrazine, which cleanly led to the formation of 15 (82%
yield). This adduct, which has been characterized by single-
crystal X-ray diffraction studies, features the more basic
nitrogen atom bonded to the electrophilic C-2 center. Clearly,
a simple deprotonation of hydrazine would occur at the
nonsubstituted nitrogen, which would have led to
adduct 16.[18]
To show that the scope of the bond activation with ethynyl
dithiocarbamate 1 is broad, 1 was reacted with diphenyldi-
sulfide, a substrate that has been used to demonstrate the
efficiency of frustrated Lewis pairs.[4,19] The reaction was
complete in 15 min at room temperature and the expected
adduct 17 was isolated in 91% yield.
These results as a whole demonstrate that a simple ethynyl
dithiocarbamate can readily activate at room temperature a
variety of bonds. This is partly due to the existence of an
equilibrium with the nonobservable mesoionic carbene
isomer, but also to the cooperative effect of the nucleophilic
and electrophilic centers of the ethynyl dithiocarbamate.
Interestingly, in the resulting adduct, the fragment of the
substrate that binds to the C-2 carbon should present a
nucleophilic character because of the presence of the other
heteroatoms. On the other hand, the bond between the C-5
Scheme 3. Reactivity of 1 with carbon dioxide and elemental sulfur,
suggesting the existence of an equilibrium between 1 and A.
Continuing our investigations, we observed that the very
weakly acidic diethylamine and diethylphosphine are cleaved
at room temperature, affording adducts 12 and 13, in 78 and
56% yield, respectively[17] (Scheme 4). In contrast, phenyl-
acetylene, which is more acidic, does not react with 1. We
verified that lithium phenylacetylide reacts with dithiolium
salt 2 to give 14 (90% yield), demonstrating that 1 and even
the putative mesoionic carbene A were not able to deproto-
nate phenylacetylene.
Since the observed reactivity of 1 does not parallel the
acidity of the substrates, we postulate that, when the latter is
9924 www.angewandte.org
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carbon and the other part of the substrate should be easily
cleaved because of the ring-opening process, which leads to
the nonbasic ethynyl dithiocarbamate. These properties open
the way for using 1 or related species as organocatalysts. This
is especially true because analogues of ethynyl dithiocarba-
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Experimental Section
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All manipulations were performed under an atmosphere of dry argon
using standard Schlenk or dry box techniques. Solvents were dried by
standard methods and distilled under argon. 1H, 19F, 11B, 31P and
13C NMR spectra were recorded on Varian Inova 500 and Bruker 300
spectrometers at 258C. Mass spectra were performed at the UC
Riverside Mass Spectrometry Laboratory. Melting points were
measured with a Bꢀchi melting point apparatus system. Ethynyl
dithiocarbamate 1 was prepared according to literature procedure.[8]
General procedure for bond activation reactions: In an NMR
tube fitted with a J. Young-type teflon valve, ethynyl dithiocarba-
mate 1 (50 mg, 0.129 mmol) was dissolved in C6D6 (1.0 mL). The
substrate (1 equivalent) was added at room temperature under inert
atmosphere. The reaction was monitored by NMR spectroscopy.
After completion of the reaction, all volatiles were removed yielding
the corresponding product. See the Supporting Information for
analytical data of all compounds.
Computational methods: The DFT calculations were carried out
with the RI-BP86 functional in conjunction with the TZVPP basis set.
The optimized structures were verified as energy minima by
calculating the vibrational frequencies. The program package Turbo-
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Received: June 22, 2011
Published online: August 16, 2011
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Keywords: bond activation · carbenes · frustrated Lewis pairs ·
homogeneous catalysis
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