Gas-phase synthesis and reactivity of Cu+-benzyne complexes

Article abstract of DOI:10.1039/c4cc04168b

Cu⁺-benzyne complexes bearing bidentate nitrogen ligands were synthesized in the gas phase for the first time using electrospray ionization mass spectrometry. The addition reactivity of copper-stabilized benzyne with amines was studied in the ion trap analyzer. The structures of products were identified by comparing their MSⁿ data with authentic compounds obtained from another generation route.

Full text of DOI:10.1039/c4cc04168b

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Gas-phase synthesis and reactivity of
+
Cu –benzyne complexes†
Cite this:DOI: 10.1039/c4cc04168b
Yunfeng Chai, Shanshan Shen, Guofeng Weng and Yuanjiang Pan*
Received 31st May 2014,
Accepted 7th August 2014
DOI: 10.1039/c4cc04168b
www.rsc.org/chemcomm
+
Cu –benzyne complexes bearing bidentate nitrogen ligands were metal–benzyne complexes formed in the liquid-phase reactions
synthesized in the gas phase for the first time using electrospray also contain various ligands. To mimic the properties and reactivity
ionization mass spectrometry. The addition reactivity of copper- of metal–benzyne complexes in the liquid-phase, synthesis of ligand-
stabilized benzyne with amines was studied in the ion trap analyzer. ligated metal–benzyne complexes is more desirable, which cannot
n
The structures of products were identified by comparing their MS data be achieved using the previous methodologies. Copper is one of the
with authentic compounds obtained from another generation route.
most used transition metals in organometallic chemistry, but it has
been rarely used in benzyne chemistry and no gaseous Cu –benzyne
+
1
Benzyne (1,2-didehydrobenzene) is a fundamental and highly complex has been reported. We therefore initiated a research
+
reactive organic intermediate that has been used in the efficient program to synthesize ligand-ligated Cu –benzyne complexes in
2–5
syntheses of various organic compounds. Since the discovery of the gas phase and study the reaction of copper-stabilized benzyne
this fascinating species, experimental and theoretical investigations with amines.
of its physical properties, chemical reactivity, and electronic
structures have received tremendous attention.
In recent years, electrospray ionization (ESI) mass spectro-
meters have become not only versatile analytical instruments but
A free benzyne cannot be isolated in solution, so its existence also useful tools in synthesizing novel and reactive gas-phase
3
0–37
in chemical reactions is usually identified by using capture ions.
Chemical reactions under atmospheric pressure by
agents. Coordination with transition metals can relieve the using (modified) ESI can yield impressive results. The reaction is
3
8–41
strain in benzyne, and the commonly used transition metals sometimes more efficient than that carried out in solution.
6
–14
are group 4 and 10 metals (Ti, Zr, Ni, and Pd) and others.
ESI mass spectrometry is a potential method to prepare gaseous
+
Isolating and trapping benzyne is less problematic in the gas ligand-ligated Cu –benzyne complexes.
phase, but the reported methods are very limited. A neutral
The metal-mediated decarboxylative reaction is a powerful
benzyne generated in a molecular beam has a lifetime of 400 ps strategy to generate organometallic intermediates both in the
1
5
32–37,42–47
only. Two strategies have been used to stabilize and capture condensed phase and in the gas phase.
In the present
gaseous benzyne in mass spectrometers, one is introducing a study, 2-iodobenzoic acid, copper, and a nitrogen-containing
positive or negative charge (group) on the phenyl ring to generate bidentate compound were used as the benzyne precursor, the
1
6–18
ring-charged benzyne analogues,
the other is utilizing a central transition metal, and the ligand, respectively. A ternary
1
9–24
2+
metal ion (Fe, Sc, Cr, etc.) to coordinate with benzyne.
In complex consisting of 2-iodobenzoic acid, Cu , and a ligand
the latter method, bare metal–benzyne complexes can be formed can be easily transferred from solution to gas phase via ESI.
and their reactivities with simple organic molecules such as Collision-induced dissociation (CID) of this complex (the single
6
3
hydrocarbons can be studied using electron (or laser) ionization isotope ion with the Cu was isolated and used in MS/MS)
Fourier-transform ion cyclotron mass spectrometry. Although undergoes decarboxylation and deiodination to generate a
6
3
+
the solvent-free environment of gas-phase experiments does not [benzyneꢀ ꢀ ꢀ Cu ꢀ ꢀ ꢀLigand] complex (A3 shown in Scheme 1).
have preparative-scale synthetic utility, it provides challenging
The CID mass spectrum (L = 1,10-phenanthroline) is shown
2
5–29
information for mechanistic interpretation.
Almost all the in Fig. 1a and the elemental composition of these four ions
(
m/z 490, 446, 319, and 243) was confirmed by high resolution
3
mass spectrometry (Fig. S1, ESI†). The MS spectrum shown in
Fig. 1b confirms the existence of benzyne in complex A3
because benzyne can be released from A3 upon collisional
activation to form A4 (76 Da neutral loss). Carboxyl and iodine
Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang, China.
E-mail: panyuanjiang@zju.edu.cn
†
Electronic supplementary information (ESI) available: Experimental and com-
putational details and Fig. S1–S17. See DOI: 10.1039/c4cc04168b
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Scheme 1 Gas-phase synthesis of the ligand-ligated Cu –benzyne complex
A3) using ESI mass spectrometry.
(
+
Scheme 2 Gas-phase synthesis of the Cu –benzyne complex and its
reaction with 2-AMP.
2,2-bipyridine (Fig. S9–S11, ESI†). After the synthesis of benzyne, its
reactivity can be further evaluated through the collisional activation
of the copper-bound benzyne–ligand complex. The benzyne is a
highly unsaturated species that easily undergoes addition reactions
such as the Diels–Alder reaction, cycloadditions with 1,3-dipoles,
and nucleophilic additions. If the ligand within the complex,
+
[
benzyneꢀꢀꢀCu ꢀꢀꢀL], is purposefully chosen, the reaction between
the benzyne and the ligand can occur. The central copper may
function as an activation center leading to some particular reactions.
The representative reactivity of benzyne is its addition reaction
with amines. When 2-AMP is used as the ligand, in the intermediate
benzyne complex (B2), the benzyne can insert into the N–H bond
of 2-AMP to give product P1 (Scheme 2). The structure of a gas-
phase ion can be identified via multi-stage mass spectrometry by
comparison with an authentic compound obtained from another
route. The CID fragmentation behavior and the energy resolved
mass spectra of P1 are in accordance with those of B4 which are
generated via ESI of a methanol solution containing N-(pyridin-
Fig. 1 CID mass spectra of (a) A1 (m/z 490) and (b) A3 (m/z 319) (L = 1,10-
phenanthroline, Cu = Cu).
63
are both excellent leaving groups in CID, so there are two
possible routes from A1 to A3 as shown in Scheme 1. Theoretical
46,47
calculations were used to find the optimal route (Fig. S2, ESI†).
The results indicate that the loss of CO is more favorable than the
2
ꢁ
loss of I in terms of energy in the first step. The relative energy
ꢂ1
of A2 plus CO
1
2
ꢂ1
is only 33.7 kJ mol higher than that of A1 and
0 ꢁ
56.1 kJ mol lower than that of A2 plus I . These results are
consistent with the experimental data showing that A2 is observed
2-ylmethyl)aniline and CuI (Fig. S12 and S13, ESI†).
0
in the MS/MS spectrum but A2 is not observed (Fig. 1a).
When TMEDA is used as the ligand, benzyne can react with
The generation of benzyne depends on the removal of the
two adjacent groups on the phenyl ring. Benzoic acid cannot be
used as a benzyne precursor in the above method (Fig. S3,
ESI†), which indicates that the ortho-iodine as a leaving group is
very important. Then, more ortho-halogenated benzoic acids
were tentatively used as benzyne precursors (Fig. S4–S6, ESI†).
For example, 2-bromobenzoic acid can be used to produce the
benzyne complex (A3), although the efficiency is much lower. In
addition, 2-chlorobenzoic acid and 2-fluorobenzoic acid cannot
be used to produce the benzyne complex (A3). The proposed
mechanism for the dehalogenation step involves losing halogen as a
TMEDA to form a covalent compound, P2 (Scheme 3). According to
the best of our knowledge on the reactivity of benzyne, the reaction
may proceed via a C–H or C–N bond insertion mechanism to
0
0
generate N-benzyl-N,N ,N -trimethylethylenediamine or N-(2-methyl-
0
0
phenyl)-N,N ,N -trimethylethylenediamine, respectively. These two
2+
radical (tendency: I 4 Br 4 Cl 4 F) and the reduction of Cu to
+
Cu . Therefore, iodine is the best leaving group among the halogens
and 2-iodobenzoic acid is an excellent ortho-benzyne precursor
in the gas phase. However, this method cannot be used to
prepare meta-benzyne and para-benzyne using 3-iodobenzoic
acid and 4-iodobenzoic acid as the potential precursors, respectively
(Fig. S7 and S8, ESI†).
Various ligands are applicable in the gas-phase synthesis of
+
0
0
+
Cu –benzyne complexes, such as N,N,N ,N -tetramethylethyl-
Scheme 3 Gas-phase synthesis of the Cu –benzyne complex and its
enediamine (TMEDA), 2-(aminomethyl)pyridine (2-AMP), and reaction with TMEDA.
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phase. The formation and reaction of benzyne in these complexes
were well proved by multi-stage mass spectrometry in combination
with theoretical calculations. This new method is promising to
synthesize more metal–benzyne complexes bearing various ligands
and then to study their gas-phase chemistry.
This study was supported by the National Science Founda-
tion of China (21025207 and 21372199).
+
Scheme 4 Gas-phase synthesis of the Cu –benzyne complex and its
reaction with N-(pyridin-2-ylmethylene)methanamine.
Notes and references
1
Three isomers are possible for benzyne: o-benzyne (1,2-didehydro-
benzene), m-benzyne (1,3-didehydrobenzene), and p-benzyne (1,4-
didehydrobenzene). When we discuss benzyne (also in this commu-
nication), it usually refers to o-benzyne.
compounds were then synthesized in solution and their complexes
with Cu (C3 and C4) can be readily produced via ESI. The multi-
+
stage fragmentation behavior of P2 is the same as that of C3 but
quite different from that of C4 (Fig. S14 and S15, ESI†). The major
product ion in the fragmentation of C3 and P2 is formed by losing
toluene (92 Da), which indicates an existing benzyl group in their
corresponding structures. These results indicate that the copper-
stabilized benzyne reacts with TMEDA via a selective C–H bond
insertion mechanism.
By applying the same approaches, the reaction of Cu –benzyne
with N-(pyridin-2-ylmethylene)methanamine was studied. The
benzyne was expected to react with this ligand through C–H
2
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