A palladium(II) Center activates nitrile ligands toward 1,3-dipolar cycloaddition of nitrones substantially more than the corresponding platinum(II) center

Article abstract of DOI:10.1021/ic301866y

Palladium(II)-coordinated NCR¹ (R¹ = Et (1), NMe ₂ (2), Ph (3)) species react smoothly with acyclic nitrones such as the ketonitrones Ph₂C=N(O)R⁴ (R⁴ = p-MeC ₆H₄ (4), p-ClC₆H₄ (5)) and the aldonitrone p-MeC₆H₄CH=N(O)Me (6) in the corresponding nitrile media. This reaction proceeds as a consecutive two-step intermolecular cycloaddition to give the mono- and bis-2,3-dihydro-1,2,4-oxadiazole complexes [PdCl₂(R¹CN){N^a=C(R¹)ON(R ⁴)C^b(R²R³)}]^(a-b) (7a-13a; R², R³ = Ph; R⁴ = C₆H ₄Me-p, R¹ = Et (7), NMe₂ (8), Ph (9); R ⁴ = C₆H₄Cl-p, R¹ = Et (10), NMe ₂ (11), Ph (12); R² = H, R³ = C ₆H₄Me-p, R⁴ = Me, R¹ = NMe ₂ (13)) and [PdCl₂{N^a=C(R¹)ON(R ⁴)C^b(R²R³)}₂] ^(a-b) (7b-13b), respectively. Inspection of the obtained data and their comparison with the previous results indicate that the Pd^II centers provide substantially greater activation of RCN ligands toward the 1,3-dipolar cycloaddition than the relevant Pt^II centers. The palladium(II)-mediated 1,3-dipolar cycloaddition of ketonitrones to nitriles is reversible. All complexes were characterized by elemental analyses (C, H, N), high-resolution ESI-MS, and IR and ¹H and ¹³C{ ¹H} NMR spectroscopy. The structure of trans-7b was determined by single-crystal X-ray diffraction. Metal-free 5-NR′₂-2,3- dihydro-1,2,4-oxadiazoles (7c-13c) were liberated from the corresponding (2,3-dihydro-1,2,4-oxadiazole)₂Pd^II complexes by treatment with 1,2-(diphenylphosphino)ethane, and the heterocycles were characterized by high-resolution ESI⁺-MS and ¹H and ¹³C{ ¹H} spectroscopy.

Full text of DOI:10.1021/ic301866y

Article
pubs.acs.org/IC
A Palladium(II) Center Activates Nitrile Ligands toward 1,3-Dipolar
Cycloaddition of Nitrones Substantially More than the
Corresponding Platinum(II) Center
Andreii S. Kritchenkov,† Nadezhda A. Bokach,*,† Galina L. Starova,† and Vadim Yu. Kukushkin*,†,‡
†Department of Chemistry, St. Petersburg State University, Universitetsky Pr. 26, 198504 Stary Petergof, Russian Federation
‡Institute of Macromolecular Compounds of Russian Academy of Sciences, V.O. Bolshoii Pr. 31, 199004 St. Petersburg, Russian
Federation
S
* Supporting Information
ABSTRACT: Palladium(II)-coordinated NCR1 (R1 = Et (1), NMe2 (2), Ph
(3)) species react smoothly with acyclic nitrones such as the ketonitrones
Ph2CN(O)R4 (R4 = p-MeC6H4 (4), p-ClC6H4 (5)) and the aldonitrone p-
MeC6H4CHN(O)Me (6) in the corresponding nitrile media. This reaction
proceeds as a consecutive two-step intermolecular cycloaddition to give the
mono- and bis-2,3-dihydro-1,2,4-oxadiazole complexes [PdCl2(R1CN){Na
C(R1)ON(R4)Cb(R2R3)}](a−b) (7a−13a; R2, R3 = Ph; R4 = C6H4Me-p, R1 = Et
(7), NMe2 (8), Ph (9); R4 = C6H4Cl-p, R1 = Et (10), NMe2 (11), Ph (12); R2 =
H, R3 = C6H4Me-p, R4 = Me, R1 = NMe2 (13)) and [PdCl2{Na
C(R1)ON(R4)Cb(R2R3)}2](a−b) (7b−13b), respectively. Inspection of the
obtained data and their comparison with the previous results indicate that the
PdII centers provide substantially greater activation of RCN ligands toward the
1,3-dipolar cycloaddition than the relevant PtII centers. The palladium(II)-
mediated 1,3-dipolar cycloaddition of ketonitrones to nitriles is reversible. All
complexes were characterized by elemental analyses (C, H, N), high-resolution
ESI-MS, and IR and 1H and 13C{1H} NMR spectroscopy. The structure of trans-
7b was determined by single-crystal X-ray diffraction. Metal-free 5-NR′2-2,3-
dihydro-1,2,4-oxadiazoles (7c−13c) were liberated from the corresponding (2,3-dihydro-1,2,4-oxadiazole)2PdII complexes by
treatment with 1,2-(diphenylphosphino)ethane, and the heterocycles were characterized by high-resolution ESI+-MS and 1H and
13C{1H} spectroscopy.
center. The nitrones are widely applied as 1,3-dipoles for both
metal-free and metal-mediated generation of cyclic systems.8
The nature and oxidation state of the metal centers play major
roles in the control of the metal-mediated CA of nitrones.
Thus, the 1,3-dipolar cycloaddition (DCA) proceeds easily
under mild conditions only when nitriles are bound to
platinum(II) or -(IV) and, in exceptional cases, to palladium-
(II) centers.2c,5b,7c,9 However, the application of highly labile
(nitrile)MIV (M = Ti, Zr) complexes leads to the substitution of
the nitrile ligands followed by some secondary processes.9e
On the basis of quantum chemical calculations10 one can
conclude that PdII centerssimilarly to the relevant PtII
centersshould also facilitate CAs. However, the greater
kinetic lability of palladium(II) species and their higher
hardness make the alternative reaction of nitrones, i.e.
substitution of nitrile ligands with nitrones,5b quite probable.
All these, in turn, significantly lower the selectivity of
palladium(II)-mediated DCA, especially when the reaction is
INTRODUCTION
■
Nitriles exhibit a relatively high chemical inertness, but
coordination of these species to a metal center dramatically
enhances their reactivity in such a way that the reaction
acceleration may reach a factor of 106−1010 and occasionally be
even as high as 1018.1−3 The systematic experimental and
theoretical studies on the reactivity of metal-bound nitriles
toward nucleophiles, electrophiles, or, eventually, 1,3-dipoles in
cycloadditions (CAs) demonstrated that the metal activation of
RCN molecules opens up attractive routes for the generation of
a great variety of compounds, i.e. iminoacylated O-, N-, and S-
nucleophiles, carboxamides (including acrylamide and nicoti-
namide), azavinylidenes, tetrazoles, oxadiazoles, oxadiazolines,
and cyanoolefins; many of these species are of significant basic,
industrial, and/or pharmacological importance.1−3
Currently a great amount of data regarding metal-mediated
and metal-catalyzed cycloadditions to various organic substrates
has been accumulated in the literature.4 In particular, the
activation of nitriles RCN, even unreactive species bearing the
electron donor R, toward cycloadditions of allyl anion dipoles
(e.g., nitrones2c,5−7) can be achieved by their ligation to a metal
Received: August 27, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ic301866y | Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
Scheme 1. Studied Cycloadditions
performed in non-nitrile solvents.5b Thus, the essential goal of
this work was directed to provide insights into the reactivity of
the palladium-bound nitriles in CA vs substitution.
Table 1. Compound Numbering to Scheme 1
R2/R3/R4
Ph/Ph/C6H4Me-p
(4)
Ph/Ph/C6H4Cl-p
(5)
H/C6H4Me-p/Me
(6)
In order to provide a greater control in palladium(II)-
mediated DCA of nitrones to ligated nitriles and to direct the
interplay of the reactants to the CA route, we suggested
employing the following dipolarophile−dipole couples: (i) the
so-called push−pull nitrile5d (Me2NCN), and the conventional
nitriles RCN (R = Et, Ph), as dipolarophiles and (ii) the aryl
ketonitrones Ph2CN(O)R4 as 1,3-dipoles. In general, the
R2NCN species are much better σ-donor ligands as compared
to the conventional alkyl and aryl cyanides; the latter behave as
only moderate net σ and π donors and are easily displaced by
stronger ligands.11 It is also important that dialkylcyanamide
ligands are more reactive toward the DCA of nitrones than the
alkylnitrile ligands.5e We were interested in a comparison of
their reactivity and selectivity of DCA at palladium(II) centers.
As dipoles, in addition to the aldonitrone, we addressed the
little studied aryl ketonitrones, insofar as these dipoles are
much more reactive in CA than the relevant aldonitrones
conventionally used for studies of these reactions.5e Further-
more, we were interested in a comparison of their reactivity
with RCN species at palladium(II) and platinum(II) metal
centers.
Our goal was at least 4-fold: (i) to compare the effects of the
nature of reactant(s) substituents for PdII-mediated DCA with
those of the previously studied platinum(II)-based systems, (ii)
to develop preparative experiments to compare the effect of the
activation of nitrile ligands by PdII and PtII centers toward DCA
of the nitrones, (iii) to develop a method of synthesis of 2,3-
dihydro-1,2,4-oxadiazoles, consisting of metal-mediated DCA
nitrones to nitriles followed by liberation of the heterocycle,
and (iv) to study the possibility of a reversible PdII-mediated
DCA.
R1
Et (1)
7a−c
8a−c
9a−c
10a−c
11a−c
12a−c
NMe2 (2)
Ph (3)
13a−c
corresponding nitrile, and they lead to the generation of 2,3-
dihydro-1,2,4-oxadiazole complexes 7a−13a and 7b−13b. It
should be pointed out that nitrones 4−6 do not react with
uncomplexed nitriles R1CN even under drastic conditions (240
h, reflux in the R1CN media). The latter observation means that
CA of the ketonitrones to the nitriles is PdII-mediated.
Although CA studied in this work is of general character, it
proceed differently depending on (i) the nature of substituents
in the R1CN ligands, (ii) the nature of dipoles, viz., with the
ketonitrones Ph2CN(O)R4 or with the aldonitrone p-
MeC6H4C(H)N(O)Me, and (iii) reaction conditions, such
as the molar ratio of reactants and temperature. All these
specific features are discussed in the following sections.
Reaction of Complexes 1−3 and Ketonitrones 4 or 5 in a
1:1 Molar Ratio. Ketonitrones 4 and 5 react with the nitrile
R1CN (R1 = Et, Ph, NMe2) ligand in 1−3 in a 1:1 molar ratio
in a solution of the corresponding nitrile, and this reaction leads
to mono-cycloadducts (mono-CAs) 7a−12a (Scheme 1, route
A).
Thus, the reaction between 4 or 5 and complex 3 in a 1:1
molar ratio in PhCN proceeds at room temperature for 30 min
to give mono-CAs 9a and 12a in 88−90% yield. In contrast to
the case for 3, CA between 1 and 2 and ketonitrones 4 and 5
(in all possible combinations) in a 1:1 molar ratio at room
temperature in EtCN or NCNMe2, respectively, does not
proceed selectively and brings about a broad mixture of
products. Monitoring of this mixture by high-resolution ESI+-
MS allowed the identification of (i) mono-CAs 7a, 8a, 10a, and
11a (see the Experimental Section), (ii) Ph2CO (m/z 107.0495
([M + H]+, calcd 107.0491), and (iii) [PdCl2{ON(R4)
CPh2}2] (R4 = C6H4Me-p, m/z 431.0123 [M − Cl]+, calcd
431.0127; R4 = C6H4Cl-p, m/z 450.9583 [M − Cl]+, calcd
450.9581). Benzophenone is apparently formed via a gradual
PdII-mediated degradation of the ketonitrones, while the
nitrone complex [PdCl2{ON(R4)CPh2}2] originates from
the substitution of the nitrile ligands in their palladium(II)
complexes 1 and 2 with the ketonitrones; although ketonitrones
RESULTS AND DISCUSSION
■
Palladium(II)-Mediated 1,3-Dipolar Cycloaddition. In
the current work, the nitrile complexes [PdCl2(NCR1)2] (R1 =
Et (1), NMe2 (2), Ph (3)) on one hand and the ketonitrones
Ph2CN(O)R4 (R4 = p-MeC6H4 (4), p-ClC6H4 (5)) and the
aldonitrone p-MeC6H4CHN(O)Me (6) on the other were
employed as the reactants for the cycloaddition study (Scheme
1 and Table 1).
The reactions between 4−6 and the nitrile ligands R1CN (R
= Et, NMe2, Ph) in their palladium(II) complexes (1−3), in all
possible combinations, were performed in a solution of the
B
dx.doi.org/10.1021/ic301866y | Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
Scheme 2. Nitrile Exchange in 7b (or 9b) via Retrocycloaddition
bound to PdII centers are unknown, PdII species bearing similar
O-coordinated aldonitrones have been previously described.5b
A decrease of the reaction temperature to −20 °C allowed
the selective generation of 7a, 8a, 10a, and 11a from 1 (or 2)
and 4 (or 5) (molar ratio 1:1.3, in a solution of the
corresponding nitrile), and these species were isolated in
good yields (ca. 70% after recrystallization). Substitution of the
nitrile ligands by the ketonitrones under these conditions was
not observed.
those for a NCNMe2 ligand in 2 and furnishes the bis-CA in
moderate yields (10−20%).5b This difference indicates a higher
dipolarophilicity of dialkylcyanamide ligands as compared to a
conventional nitrile such as MeCN toward aldonitrones, and
this observation is also in agreement with the data described
earlier for PtII-mediated DCA.5d In addition, dialkylcyanamides
are stronger σ donors than nitriles (Pickett parameter(s) for
NCNR2 range from −0.23 to −0.58 and for NCMe is −0.8511),
which disfavors the substitution with aldonitrones and makes
DCA to the nitrile functionality more selective for NCNMe2
than for the poorer donor MeCN or EtCN ligands.
We also conducted a comparative study of the reactivity of
the complexes trans-[MCl2(R1CN)2] (M = Pd, Pt) in the
reaction with the nitrones. Thus, the reaction between trans-
[MCl2(PhCN)2] and ketonitrones 4 or 5 (molar ratio 1:1,
room temperature, in PhCN) is complete in 0.5 h (M = Pd)
and does not proceed at all (M = Pt). The reaction between
trans-[MCl2(R1CN)2] (R1 = Et, NMe2) and ketonitrones 4 and
5 (molar ratio 1:1 in R1CN or in CHCl35e) is complete in 4 h
(R1 = NMe2) and 6 h (R1 = Et) at −20 °C (M = Pd) or at
room temperature when M = Pt. All observations indicate the
higher degree of activation of nitrile ligands toward DCA of
ketonitrones by the PdII as compared to the PtII center.
Reaction of Complexes 1−3 with Ketonitrones 4 and 5 in
a 1:2 Molar Ratio. When the molar ratio between palladium
complexes 1−3 and the ketonitrones is 1:2, the reaction leads
to bis-cycloadducts (bis-CAs) 7b−12b (Scheme 1, route C).
This interaction is a consecutive two-step cycloaddition
(Scheme 1, routes A and B). Indeed, the treatment of 1
equiv of 7a−12a with 1 equiv of 4 (or 5) in the corresponding
nitrile solution leads to selective generation of 7b−12b.
The interaction of complex 3 and ketonitrones 4 or 5 and in
a 1:2 molar ratio in PhCN proceeds at room temperature for 1
h to furnish bis-CAs 9b and 12b, isolated in 88−92% yields.
The reaction between complexes 1 and 2 and ketonitrones 4
and 5 in the neat nitriles EtCN and NCNMe2, respectively, in a
1:2 molar ratio is complete in ca. 4 h at room temperature to
give yellow precipitates of 7b, 8b, 10b, and 11b in rather high
yields (ca. 80−90%).
Reaction of Complex 2 with Aldonitrone 6. Although the
PdII-mediated DCA of aldonitrones to the conventional (alkyl
and aryl) nitrile ligands is known,5b,9e the palladium(II)-
mediated CA of aldonitrones to the so-called push−pull nitrile
ligands (e.g., dialkylcyanamides) has not yet been investigated.
Our previous studies5d demonstrated that the platinum(II)
center efficiently activates dialkylcyanamide ligands toward
DCA of aldonitrones. Taking this into account, we attempted
the reaction between aldonitrone 6 and trans-
[PdCl2(NCNMe2)2] (2). The reaction of 2 and 6 in
NCNMe2 at room temperature is complete in 12 h to give
mono-CA 13a (molar ratio 1:1, Scheme 1, route A), and in 36
h to give bis-CA 13b (molar ratio 1:2, Scheme 1, route B).
The previous studies demonstrated that an acetonitrile ligand
in [PdCl2(MeCN)2] reacts with aldonitrone 6 under more
drastic conditions (reflux in MeCN, 1 day) as compared to
The DCA between trans-[MCl2(R1CN)2] (R1 = Me, Et) and
aldonitrone 6 (molar ratio 1:2 in R1CN) is complete in 1 day
under reflux (M = Pd) or does not proceed at all (M = Pt; 1
day, reflux). Moreover, we found that the reaction of trans-
[MCl2(NCNMe2)2] and aldonitrone 6 (molar ratio 1:1, room
temperature, in NCNMe2) is complete in 12 h (M = Pd) or in
30 h (M = Pt). These synthetic experiments again indicate the
higher degree of activation of nitriles toward DCA of
aldonitrones by PdII as compared to the corresponding PtII
center.
Reversibility of DCA. The completeness and the selectivity
of DCA depend on the solubility of CA products. Thus,
formation of poorly soluble bis-CAs occurs selectively with a
high degree of conversion, while generation of soluble mono-
CAs is accompanied by side reactions. These experimental
observations give collateral evidence favoring the reversibility of
DCA, and they agree well with our previous findings of the
reversibility of platinum(II)-mediated DCA.5e
To obtain data additionally supporting the reversibility, we
performed the following experiments. Complex 7b (or 9b) was
stirred in NCNMe2 solution for 2 days at room temperature,
and the progress of the transformation (Scheme 2) was
monitored by TLC. After disappearance of starting complex 7b
(or 9b), compound 14 (or 15) was isolated by column
chromatography on SiO2 (eluent CHCl3/Me2CO 40/1 v/v).
The total conversion of 7b or 9b into 11b can be achieved in
ca. 120 h. The reverse exchange also takes place, and 11b was
completely converted into 7b by keeping the former in neat
EtCN at room temperature for 7 days.
We also conducted an experiment indicating that the
reversibility of DCA is specific for the metal-bound CA species
7b and 9b derived from ketonitrones 4 and 5. Prolonged (100
h) stirring of 13b (derived from aldonitrone 6) in NCNEt2 or
in EtCN and PhCN at 35 °C gave no evidence for the
appearance of other heterocycle-containing complexes in the
mixture, and the starting materials remain intact. This
observation can be rationalized by the higher thermodynamic
stability of palladium(II)-bound 3-aryl-2,3-dihydro-1,2,4-oxa-
diazoles as compared to the ligated 3,3-diaryl-2,3-dihydro-1,2,4-
oxadiazoles, due to the absence of steric repulsions between the
phenyl groups and the metal fragment.
C
dx.doi.org/10.1021/ic301866y | Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
Figure 1. Thermal ellipsoid view of 7b with the atomic numbering scheme. Thermal ellipsoids are drawn with 50% probability.
In previous work,5e we found the first example of the metal-
mediated reversible CA of C,C,N-triaryl ketonitrones to nitrile
ligands, observed at PtII centers. Herein we have demonstrated
that the palladium(II)-mediated DCA of the ketonitrones to
nitriles can be reversible; therefore, the reversibility of metal-
mediated CA of ketonitrones to nitriles has more general
character.
Liberation of the Heterocyclic Ligands. Several methods
for the liberation of various nitrogen heterocycles from their
palladium(II) complexes have been developed, and they are
based on displacement with diphosphines,5b,7b,12 excess Na2S,5b
or methylamine.9e Earlier we performed the synthesis of the 3-
dialkylamino-2,3-dihydro-1,2,4-oxadiazoles and 3,3-diaryl-2,3-
dihydro-1,2,4-oxadiazoles that is based on platinum-mediated
CA followed by the liberation of the newly formed heterocyclic
ligands. It appears that the ligands are so strongly bound to the
platinum(II) center that their decoordination was achieved only
by the treatment of the platinum complexes with an excess of a
powerful ligand such as CN−, conducted in accord with the
Leung method.5d,e,13
In contrast to the kinetically inert platinum(II) species, the
relevant palladium(II) complexes are logically5b,9e,14 much
more labile, and in accord with our expectations, we observed
that the decoordination does not require a strong ligand such as
CN− and it can be achieved with 1,2-(diphenylphosphino)-
ethane (dppe). Indeed, the treatment of 7b−13b with 2 equiv
of dppe for 4 h at room temperature (Scheme 1, route D) leads
to almost quantitative formation of uncomplexed heterocycles
7c−13c in solution along with a colorless precipitate of the
well-known [Pd(dppe)2](Cl)2.15 Hence, palladium(II)-based
generation of 2,3-dihydro-1,2,4-oxadiazoles is much more
synthetically favorable in comparison to the approach based
on application of the appropriate platinum(II) species. First,
the palladium(II) center activates the nitrile ligands more
strongly than the PtII center, and second, the liberation of 2,3-
dihydro-1,2,4-oxadiazoles could be achieved easily and
conducted under mild conditions.
Characterization of 7a−13a and 7b−13b. Complexes
7a−13a and 7b−13b were obtained as yellow solids and
characterized by elemental analyses (C, H, N), high-resolution
1
ESI+-MS, IR and and H and 13C{1H} NMR spectroscopy and
also by X-ray diffraction (7b). All palladium species gave
satisfactory microanalyses. In the ESI+-MS, the typical ions that
were detected are [M + H]+, [M + Na]+, and [M + K]+. A
comparison of the IR spectra of the products with those of
starting 1−3 indicated the absence of ν(CN) stretching
vibrations at ca. 2300 cm−1 for 7b−13b, while for 7a−13a these
stretches are displayed in the expected region from 2290 to
2310 cm−1. The presence of intense ν(CN) vibrations in the
range between 1630 and 1667 cm−1 was detected in the IR
spectra of all complexes.
For 7a−13a and 7b−13b signal integrations in the 1H NMR
spectra give evidence that the reaction between each of the
coordinated nitriles and the nitrone proceeds in a 1:1 ratio.
1
Both H and 13C{1H} NMR spectra of 7a−13a exhibit signals
from the 2,3-dihydro-1,2,4-oxadiazole and the nitrile ligands.
The 1H NMR spectra of 8a, 11a, and 13a display broad (owing
to hindered rotation around the C3−NMe2 bond) singlets of
the CH3 protons from C3−NMe2 (3.63−3.78 ppm). The less
broad signals from these protons of bis-CA species are shifted
to low field by 0.53−0.69 ppm, relative to the corresponding
signals from mono-CAs. In the 1H NMR spectra of 7a, 10a and
7b, 10b, the quartets due to the CH2 protons from the C3−Et
atom appeared in almost the same range as for mono- and bis-
CA species. In the 13C{1H} NMR spectra, peaks due to C5N
(158.4−166.8 ppm) and C3 (98.1−98.6 ppm) were recognized.
Complex 7b was additionally characterized by single-crystal
X-ray diffraction (Figure 1). In 7b, the coordination polyhedron
of the Pd atom is a slightly distorted square plane with the
heterocyclic ligands in trans positions. The Pd−N(4) bond
(2.038(3) Å) is typical for (imine)PdII species,16 while the Pd−
Cl bond (2.2851(11) Å) is specific for palladium(II)
chlorides.16 The N(4)−C(5) distance (1.252(5) Å) is
characteristic for a NC double bond,16 while the N(4)−
C(3) (1.508(4) Å) and the N(2)−C(3) distances (1.523(5) Å)
D
dx.doi.org/10.1021/ic301866y | Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
are specific for a typical N−C single bond, and all these
distances are close to related bond lengths in the previously
reported5e (2,3-dihydro-1,2,4-oxadiazole)2PtII complex (N(4)−
C(5) = 1.283(3)Å, N(4)−C(3) = 1.492(3)Å, N(2)−C(3) =
1.519(3) Å). In the crystal structure of 7b, pseudolayers of
{Cl2Pt} and fragments of the organic ligand (parallel to plane
yz) were found (Figure S1, Supporting Information). The Cl
atoms interact with the neighboring molecules via C−H···Cl
contacts; one of them is a rather strong bond, and the other
one forms the hydrogen bridge (Table S1 and Figure S2,
Supporting Information).
[M(en)2]2+ centers; the rate of the water addition found for M
= PdII was substantially higher than for M = PtII. However, our
experimental results along with literature data on metal-
mediated DCA should be further interpreted theoretically and
appropriate calculations are on the way in our group.
Third, the directing of the interplay of nitrones to either CA
to nitrile ligands or a nitrile substitution route depends on a
delicate balance between the donor/acceptor properties of
substituents at both reactants, the activating power of the metal
center toward DCA, and its substitution inertness/lability
toward interaction with the reactants. From this perspective the
PdII center occupies an intermediate position between
substitutionally inert, strong RCN activators such as PtII and
PtIV centers (where only selective cycloaddition of both
nitrones and nitrile oxides2c was observed) and kinetically
labile nitrile TiIV and ZrIV systems (where only displacement of
nitriles by nitrones was found).9e
Fourth, CA of the nitrones to the push−pull dialkylcyana-
mide systems proceeds differently as compared to CA with the
conventional alkyl- and arylnitriles. Thus, in the case of R2NCN
ligands at palladium(II) (this work) and platinum(II)5d,e
centers we always observed a higher selectivity of CA that
might be associated with better σ-donor properties of these
species as compared to RCN species11 that make the side
substitution reaction with nitrones less favorable.
Characterization of 14 and 15. Complexes 14 and 15
were obtained as yellow solids and characterized by elemental
1
analyses (C, H, N), high-resolution ESI+-MS, and IR and H
and 13C{1H} NMR spectroscopy. All palladium species gave
satisfactory microanalyses. In the high-resolution ESI+-MS, the
typical ions [M + Na]+ were detected. The presence of intense
ν(CN) vibrations at 1658 (14) and 1651 cm−1 (15) was
1
detected in the IR spectra of the complexes. The H NMR
spectra of 14 and 15 display broad (owing to hindered rotation
around the C3−NMe2 bond) singlets of the CH3 protons from
C3−NMe2 (3.06−3.08 ppm). In the 1H NMR spectra of 14, the
quartet due to the CH2 protons from C3−Et was detected. In
the 13C{1H} NMR spectra, peaks due to C5N (161.0−162.3)
and C3 (98.3−98.5 ppm) were recognized.
Characterization of 9c−12c. Although 7c, 8c, and 13c are
known and their preparation and characterization has been
described recently by us,5d,e the new metal-free 2,3-dihydro-
1,2,4-oxadiazole species 9c−12c were characterized by high-
Fifth, we developed a two-step procedure for the previously
unknown 3,3-diaryl-2,3-dihydro-1,2,4-oxadiazoles via PdII (this
work)- and PtII-mediated5e generation of the ligated hetero-
cycles followed by the liberation of dihydrooxadiazole species
by the displacement with 1,2-(diphenylphosphino)ethane (this
work) or NaCN.5e The palladium(II)-based system has obvious
advantages over the platinum system. Indeed, the PdII center
provides a higher activation of RCN species and CA could be
performed under milder conditions. Furthermore, the liberation
of PdII-bound oxadiazoles is much easier as compared to that of
the PtII systems. It is also important that the palladium(II)-
based procedure is more cost efficient that the platinum
method.
Further studies may be associated with the search for more
labile and low-cost 3d metal systems for metal-mediated or, in
the most advantageous case, metal-catalyzed DCA. In addition,
we will attempt CA of less usual and rather inert dipoles, whose
interplay with metal-free RCN species is yet unknown and even
hardly possible.
1
resolution ESI+ mass spectrometry and H and 13C{1H} NMR
spectroscopy. In the ESI+-MS, the observed peaks were
attributed to [M + H]+ and [M + Na]+. 13C{1H} NMR spectra
of the 2,3-dihydro-1,2,4-oxadiazoles demonstrate all signals
specific for these heterocycles; the liberated species exhibit
characteristic signals from C3a (96.3−97.5 ppm) and CN
(161.2−162.0 ppm).
FINAL REMARKS
■
The results obtained in this work could be considered from a
few perspectives. First, for palladium(II)-mediated DCA, we
observed the same effects of the nature of reactant(s)
substituents as in the previously studied platinum(II)-based
systems.2c,5e Thus, PhCN and R2NCN species are more
reactive in CA than AlkCN complexes. Furthermore, the
ketonitrones are more reactive in DCA as compared to the
corresponding aldonitrones. All these findings together point
out that the switch of platinum2c,5e to palladium (this work)
does not affect the type of CA in Sustman’s classification.17 At
both metal centers it belongs to the normal electron demand
DCA, when the outcome of the reaction is determined by the
HOMOdipole−LUMOdipolarophile gap.
EXPERIMENTAL SECTION
■
Materials and Instrumentation. Solvents were obtained from
commercial sources and used as received. Complexes 1−3 were
synthesized in accord with the published procedures.20 Nitrones 4 and
5 were obtained in according with the previously described protocol21
by the reaction of aryl nitroso compounds with diphenyldiazomethane
in diethyl ether at room temperature (60−85%). Nitrone 6 was
obtained by the condensation of N-methyl hydroxylamine with p-
tolylaldehyde by the known method.22 C, H, and N elemental analyses
were carried out by the Department of Organic Chemistry of St.
Petersburg State University on a Hewlett-Packard 185B Carbon
Hydrogen Nitrogen Analyzer. Electrospray ionization mass spectra
were obtained on a Bruker micrOTOF spectrometer equipped with an
electrospray ionization (ESI) source. The instrument was operated in
both positive and negative ion modes using a m/z range of 50−3000.
The capillary voltage of the ion source was set at −4500 V (ESI+-MS)
and the capillary exit at (70−150) V. For ESI species were dissolved
in MeCN; NaBF4 or formic acid was used as addition ionization agent.
In the isotopic pattern, the most intense peak is reported. TLC was
performed on Merck 60 F254 SiO2 plates. Infrared spectra (4000−400
Second, inspection of the data obtained for palladium(II) and
previous results on the corresponding platinum(II)-based
systems explicitly indicate that, under strictly similar conditions,
PdII centers provide substantially higher activation of RCN
ligands toward CA than the relevant PtII centers. Taking into
account the significant increase of asynchronicity in CA of
nitrones to ligated nitrile species as compared to CA of metal-
free reactants,14,18 the former type of cycloaddition resembles
the nucleophilic addition to metal-activated nitriles. In this
context, it is worth mentioning that a similar trend in reactivity
upon alteration of metal centers was observed by Lippert and
colleagues,19 who studied the hydration of nitriles ligated to
E
dx.doi.org/10.1021/ic301866y | Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
cm−1) were recorded on a Shimadzu FTIR-8400S instrument as KBr
pellets. 1H and 13C NMR spectra were measured in CDCl3 on a
Bruker DPX-300 spectrometer at ambient temperature.
C6H4Me-p), 23.2 (CH2 from Et of the 2,3-dihydro-1,2,4-oxadiazole
ligand), 98.4 (N−C−N), 121.0, 124.8, 127.5, 129.0, 129.5, 131.5,
135.0, and 141.1 (Caromatic), 162.2 (C(O)N); the CN carbon was
not detected.
8a: 51.1 mg, 85%. Anal. Found: C, 51.62; H, 4.84; N, 11.58. Calcd
for C26H29N5Cl2OPd: C, 51.63; H, 4.83; N, 11.58). High-resolution
ESI+: m/z 607.0958 ([M + H]+ requires 607.0956). The complex
X-ray Structure Determination. The XRD single-crystal experi-
ment was conducted at the X-ray Diffraction Center of St. Petersburg
State University. The X-ray diffraction data were collected on a Bruker
Kappa Apex II DUO diffractometer using Mo Kα radiation (λ = 0.710
73 Å) at 100 K. APEX223 software packages were used for cell
refinements and data reductions. The structures were solved by direct
methods using the SIR-9224 program with the WinGX25 graphical user
interface. A semiempirical absorption correction (SADABS)26 was
applied. Structural refinements were carried out using SHELXL-97.27
The hydrogens were positioned geometrically and constrained to ride
on their parent atoms, with C−H = 0.95−0.99 Å and Uiso = 1.2−
1.5Ueq (parent atom) (Table S2, Supporting Information).
Synthetic Work. Reaction of Complexes 1−3 with Nitrones 4−6
in a 1:1 Molar Ratio. A solution of 4 or 5 (0.1 mmol) in the
corresponding nitrile R1CN (R1 = Et, NMe2, Ph; 1 mL) was added to
a solution of [PdCl2(R1CN)2] (1−3: 0.13 mmol, R1 = Et; 0.01 mmol,
R1 = Ph, NMe2) in R1CN (1 mL). The reaction mixture was stirred at
−20 °C (R1 = Et, NMe2) or room temperature (R1 = Ph) for 30 min
(R1 = Ph), 4 h (R1 = NMe2), or 6 h (R1 = Et). In the cases of R1 = Et,
NMe2, the solvent was evaporated in vacuo at room temperature to
give oily residues. Complexes 7a and 10a were purified by
recrystallization from CHCl3/n-hexane (4/1 v/v), while the yellow
residues of 8a and 11a were crystallized under a layer of n-hexane at
room temperature and washed with three 5 mL portions of a n-
hexane/Et2O mixture (4/1 v/v). For R1 = Ph, 10 mL of n-hexane was
added at the end of the reaction, whereupon the yellow precipitates of
9a and 12a were separated by filtration. The yellow powders of 7a−
12a were dried in air at room temperature. Yields: 69−88%.
A solution of the nitrone p-MeC6H4CHN(O)Me (0.1 mmol) in
NCNMe2 (1 mL) was added to a solution of [PdCl2(NCNMe2)2] (0.1
mmol) in NCNMe2 (1 mL). The reaction mixture was stirred at room
temperature for 12 h. The solvent was evaporated in vacuo at 25 °C to
give the oily residue of 13a. The residue was crystallized under a layer
of n-hexane and washed with n-hexane/Et2O, (4/1 v/v, three 5 mL
portions) and dried in air at room temperature. Yield: 92%.
Reaction of Complexes 1−3 with Nitrones 4−6 in a 1:2 Molar
Ratio. A solution of ketonitrone 4 or 5 (0.2 mmol) in the
corresponding nitrile R1CN (R1 = Et, Ph, NMe2; 1 mL) was added
to a solution of [PdCl2(R1CN)2] (0.1 mmol) in R1CN (1 mL). The
reaction mixture was stirred at room temperature for 4 h (R1 = Et,
NMe2) or for 1 h (R1 = Ph). For R1 = Et, NMe2 the yellow precipitates
of 7b, 8b, 10b, and 11b were separated by filtration and washed with
n-hexane (three 1 mL portions). For R1 = Ph n-hexane (10 mL) was
added at the end of the reaction, whereupon the yellow precipitate of
9b or 12b was filtered off. The yellow powders of 7b−12b were dried
in air at room temperature. Yields: 88−92%.
A solution of the nitrone p-MeC6H4CHN(O)Me (0.2 mmol) in
NCNMe2 (1 mL) was added to a solution of [PdCl2(NCNMe2)2] (0.1
mmol) in NCNMe2 (1 mL). The reaction mixture was stirred at room
temperature for 36 h. The solvent was evaporated in vacuo at room
temperature to give an oily residue of 13b. The residue was crystallized
from n-hexane and washed with n-hexane/Et2O (4/1 v/v; three 5 mL
portions) and dried in air at room temperature. Yield: 91%.
Characterization of Mono-CA Species. 7a: 40.1 mg, 70%. Anal.
Found: C, 44.38; H, 4.71; N, 7.33. Calcd for C26H27N3Cl2OPd: C,
44.32; H, 4.73; N, 7.31). High-resolution ESI+: m/z 599.0666 ([M +
Na]+ requires 599.0558). The complex decomposes on SiO2, and this
prevented TLC monitoring. IR νmax/cm−1 (KBr): 2934 m (C−H),
1637 s (CN). δH (300 MHz, CDCl3): 1.29 (3H, t, J = 7.6 Hz, CH3
from Et of the 2,3-dihydro-1,2,4-oxadiazole ligand), 1.57 (3H, s, CH3
from Et of the nitrile ligand), 2.14 (3H, s, CH3 from C6H4Me-p), 2.19
(2H, s, CH2 from Et of the nitrile ligand), 2.81 (2H, q, J = 7.6 Hz, CH2
from Et of the 2,3-dihydro-1,2,4-oxadiazole ligand), 6.46 (2H, d, o-
protons from C6H4Me-p), 6.70 (2H, d, m-protons from C6H4Me-p),
7.27 and 7.50 (10H, 2 m, Haromatic). δC (75.5 MHz, CDCl3): 9.9 and
10.3 (CH3 from Et of the nitrile and the 2,3-dihydro-1,2,4-oxadiazole
ligand), 13.1 (CH2 from Et of the nitrile ligand), 21.2 (CH3 from
decomposes on SiO2, and this prevented TLC monitoring. IR νmax
/
cm−1 (KBr): 2930 m (C−H), 2310 s (CN), 1667 s (CN). δH
(300 MHz, CDCl3): 2.22 (3H, s, CH3 from C6H4Me-p), 2.86 (6H, s,
NMe2 of the nitrile ligand), 3.75 (6H, br s, NMe2 of the 2,3-dihydro-
1,2,4-oxadiazole ligand), 6.57 (2H, d, o-protons from C6H4Me-p), 6.83
(2H, d, m-protons from C6H4Me-p), 7.29, and 7.46 (10H, 2 m,
Haromatic). δC (75.5 MHz, CDCl3): 21.6 (CH3 from C6H4Me-p), 40.4,
40.6 (NMe2 of the 2,3-dihydro-1,2,4-oxadiazole ligand and of the
nitrile ligand), 98.5 (N−C−N), 121.5, 126.8, 128.1, 129.6, 132.7,
136.1, 138.2, and 141.7 (Caromatic), 161.3 (C(O)N); the CN
carbon was not detected.
9a: 58.9 mg, 88%. Anal. Found: C, 60.90; H, 4.09; N, 6.25. Calcd
for C34H27N3Cl2OPd: C, 60.87; H, 4.06; N, 6.26. High-resolution
ESI+: m/z 672.0662 ([M + Na]+ requires 672.0660). The complex
decomposes on SiO2, and this prevented TLC monitoring. IR νmax
/
cm−1 (KBr): 2933 m (C−H), 1630 s (CN). δH (300 MHz, CDCl3):
2.40 (3H, t, CH3 from p-tol), 7.19, 7.41, 7.56, 7.69, 7.72, 7.81 (24H, 6
m, Haromatic). δC (75.5 MHz, CDCl3): 10.0 (CH3 from p-tol), 98.2 (N−
C−N), 121.0, 124.6, 127.4, 129.0, 129.5, 131.6, 132.3, 133.1, 135.0,
and 141.0 (Caromatic), 162.0 (C(O)N); the CN carbon was not
detected.
10a: 40.9 mg, 69%. Anal. Found: C, 50,45; H, 4.08; N, 7.04. Calcd
for C25H24N3Cl3OPd: C, 50.44; H, 4.06; N, 7.06. High-resolution
ESI+: m/z 619.0011 ([M + Na]+ requires 619.0012). The complex
decomposes on SiO2, and this prevented TLC monitoring. IR νmax/
cm−1 (KBr): 2936 m (C−H), 1636 s (CN). δH (300 MHz, CDCl3):
1.30 (3H, t, J = 7.6 Hz, CH3 from Et of the 2,3-dihydro-1,2,4-
oxadiazole ligand), 1.57 (3H, s, CH3 from Et of the nitrile ligand), 2.19
(2H, s, CH2 from Et of the nitrile ligand), 2.82 (2H, q, J = 7.6 Hz, CH2
from Et of the 2,3-dihydro-1,2,4-oxadiazole ligand) 6.49 (2H, d, o-
protons from C6H4Cl-p), 6.88 (2H, d, m-protons from C6H4Cl-p),
7.32 and 7.50 (10H, 2 m, Haromatic). δC (75.5 MHz, CDCl3): 9.9 and
10.3 (CH3 from Et of the nitrile and the 2,3-dihydro-1,2,4-oxadiazole
ligand), 13.1 (CH2 from Et of the nitrile ligand), 22.9 (CH2 from Et of
the 2,3-dihydro-1,2,4-oxadiazole ligand), 98.3 (N−C−N), 122.8,
127.3, 126.9, 128.5, 129.2, 132.0, 137.7, and 143.1 (Caromatic), 159.7
(C(O)N); the CN carbon was not detected.
11a: 54.2 mg, 87%. Anal. Found: C, 48.04; H, 4.19; N, 11.19. Calcd
for C25H26N5Cl3OPd: C, 48.02; H, 4.19; N, 11.20. High-resolution
ESI+: m/z 649.0293 ([M + Na]+ requires 649.0297). The complex
decomposes on SiO2, and this prevented TLC monitoring. IR νmax
/
cm−1 (KBr): 2931 m (C−H), 2290 m (CN), 1664 s (CN). δH
(300 MHz, CDCl3): 2.85 (6H, s, NMe2 of the nitrile ligand), 3.78
(6H, br s, NMe2 of the 2,3-dihydro-1,2,4-oxadiazole ligand), 6.69 (2H,
d, o-protons from C6H4Cl-p), 7.03 (2H, d, m-protons from C6H4Cl-p),
7.35, and 7.62 (10H, 2 m, Haromatic). δC (75.5 MHz, CDCl3): 40.4, 40.6
(NMe2 of the 2,3-dihydro-1,2,4-oxadiazole ligand and of the nitrile
ligand), 98.4 (N−C−N), 122.3, 127.3, 128.4, 129.3, 131.2, 131.8,
137.3, and 143.0 (Caromatic), 161.3 (C(O)N); the CN carbon was
not detected.
12a: 56.7 mg, 82%. Anal. Found: C, 57.36; H, 3.49; N, 6.09. Calcd
for C33H24N3Cl3OPd: C, 57.33; H, 3.50; N, 6.08. High-resolution
ESI+: m/z 715.0011 ([M + Na]+ requires 715.0012). The complex
decomposes on SiO2, and this prevented TLC monitoring. IR νmax
/
cm−1 (KBr): 2932 m (C−H), 1630 s (CN). δH (300 MHz, CDCl3):
7.18, 7.40, 7.56, 7.69, 7.70, 7.73, 7.80 (6 m, Haromatic). δC (75.5 MHz,
CDCl3): 98.4 (N−C−N), 121.1, 124.6, 127.4, 129.1, 129.5, 131.5,
133.2, 135.2, and 141.0 (Caromatic), 162.1 (C(O)N); the CN
carbon was not detected.
13a: 38.6 mg, 92%. Anal. Found: C, 37.21; H, 4.67; N, 15.47. Calcd
for C15H23N5Cl2OPd: C, 37.15; H, 4.68; N, 15.47. High-resolution
ESI+: m/z 491.0303 ([M + Na]+ requires 491.0306). The complex
decomposes on SiO2, and this prevented TLC monitoring. IR νmax
/
F
dx.doi.org/10.1021/ic301866y | Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
cm−1 (KBr): 2931, m (C−H), 2291 m (CN), 1666 s (CN). δH
(300 MHz, CDCl3): 2.31 (3H, s, CH3 from C6H4Me-p), 2.91 (9H, br
s, N(O)Me, NMe2 of the nitrile ligand), 3.63 (6H, br s, NMe2 of the
2,3-dihydro-1,2,4-oxadiazole ligand), 5.55 (1H, s, CH), 7.17 (2H, d, m-
H from p-tol), 7.47 (2H, d, o-H from C6H4Me-p). δC (75.5 MHz,
CDCl3): 21.8 (CH3 from p-tol), 40.3 (NMe2 of the 2,3-dihydro-1,2,4-
oxadiazole ligand), 40.4 (NMe2 of the nitrile ligand), 46.2 (N(O)Me),
93.1 (N−C−N), 128.5, 129.4, 135.09, and 139.1 (Caromatic), 158.4
(C(O)N); the CN carbon was not detected.
CHCl3/Me2CO, 40/1 v/v). IR νmax/cm−1 (KBr): 2935 m (C−H),
1666 s (CN). δH (300 MHz, CDCl3): 2.32 (3H, s, CH3 from p-tol),
2.75 (3H, s, N(O)Me), 3.10 (6H, br s, NMe2), 5.39 (1H, br s, CH),
7.19 (2H, two d, m-H from C6H4Me-p), 7.40 (2H, br d, o-H from
C6H4Me-p). δC (75.5 MHz, CDCl3): 21.7 (CH3 from p-tol), 39.6
(NMe2), 44.5 (N(O)Me), 93.4 (N−CH−N), 129.1, 130.2, 135.08,
and 139.3 (Caromatic), 158.6 (C(O)N).
Reversibility Experiment and Characterization of 14 and 15. A
solution of 7b (or 9b) was stirred in NCNMe2 for 48 h, and the
progress of the reaction was monitored by TLC. Complexes 14 and 15
were isolated by column chromatography on SiO2 (Merck, 70−230
mesh; eluent CHCl3/Me2CO 40/1 v/v). The solvent was evaporated
in vacuo at room temperature to give yellow oily residues, which were
crystallized under n-hexane to form the yellow powders of 14 and 15.
The complexes were dried in air at 20−25 °C. Yields: 56−73%.
14: 48.2 mg, 56%. Anal. Found: C, 62.65; H, 5.01; N, 8.12. Calcd
for C45H43N5Cl2O2Pd: C, 62.62; H, 5.02; N, 8.11. High-resolution
ESI+: m/z 887.1821 ([M + Na]+ requires 887.1821). Rf = 0.56 (eluent
CHCl3/Me2CO, 40/1 v/v). IR νmax/cm−1 (KBr): 2933 m (C−H),
1658 s (CN). δH (300 MHz, CD2Cl2): 1.30 (3H, t, J = 7.6 Hz, CH3
from Et), 2.20 (3H, s, CH3 from C6H4Me-p of 5-Et-2,3-dihydro-1,2,4-
oxadiazole ligand), 2.40 (3H, s, CH3 from C6H4Me-p 5-Ph-2,3-
dihydro-1,2,4-oxadiazole ligand), 2.81 (2H q, J = 7.6 Hz, CH2 from
Et), 3.08 (6H, br s, NMe2), 6.46, 6.72, 7.18, 7.43, 7.63, 7.83 (28H, 6 m,
Haromatic). δC (75.5 MHz, CDCl3): 10.0 (CH3 from Et), 21.2 and 21.4
(CH3 from C6H4Me-p), 22.6 (CH2 from Et), 39.9 (NMe2), 98.3 and
98.5 (N−C−N), 122.2, 126.7, 128.6, 128.8, 132.3, 132.8, 135.8, 136.2,
138.2, and 141.3 (Caromatic), 161.2 (C(O)N).
Characterization of Bis-CA Species. 7b: 78.2 mg, 90%. Anal.
Found: 64.10; H, 5.12; N, 6.53. Calcd for C46H44N4Cl2O2Pd: C, 64.08;
H, 5.14; N, 6.50. High-resolution ESI+: m/z 902.1607 ([M + K]+
requires 902.1607). Rf = 0.39 (eluent CHCl3/Me2CO, 40/1 v/v). IR
νmax/cm−1 (KBr): 2934, 2978 m (C−H), 1643 s (CN). δH (300
MHz, CDCl3): 1.30 (3H, t, J = 7.6 Hz, CH3 from Et), 2.14 (3H, s,
CH3 from C6H4Me-p), 2.81 (2H, q, J = 7.6 Hz, CH2 from Et), 6.46
(2H, d, o-protons from C6H4Me-p), 6.70 (2H, d, m-protons from
C6H4Me-p), 7.28, and 7.50 (10H, 2 m, Haromatic). δC 10.0 (CH3 from
Et), 21.2 (CH3 from C6H4Me-p), 22.6 (CH2 from Et), 98.3 (N−C−
N),122.1, 126.7, 128.6, 128.8, 132.8, 135.8, 138.2, and 141.3 (Caromatic),
161.1 (C(O)N).
8b: 78.3 mg, 88%. Anal. Found: C, 61.97; H, 5.20; N, 9.39. Calcd
for C46H46N6Cl2O2Pd: C, 61.92; H, 5.20; N, 9.42. High-resolution
ESI+: m/z 894.2264 ([M + H]+ requires 894.2266). Rf = 0.40 (eluent
CHCl3/Me2CO, 40/1 v/v). IR νmax/cm−1 (KBr): 2933 m (C−H),
1648 s (CN). δH (300 MHz, CDCl3): 2.21 (3H, s, CH3 from
C6H4Me-p), 3.06 (6H, br s, NMe2), 6.34 (2H, d, o-protons from
C6H4Me-p), 6.77 (2H, d, m-protons from C6H4Me-p), 7.29, and 7.46
(10H, 2 m, Haromatic). δC (75.5 MHz, CDCl3): 21.5 (CH3 from
C6H4Me-p), 39.9 (NMe2), 98.5 (N−C−N), 122.3, 127.0, 128.4, 128.9,
132.3, 135.8, 138.1, and 141.8 (Caromatic), 161.2 (C(O)N).
9b: 75.5 mg, 79%. Anal. Found: C, 67.67; H, 4.66; N, 5.83. Calcd
for C54H44N4Cl2O2Pd: C, 67.68; H, 4.63; N, 5.85. High-resolution
ESI+: m/z 982.1864 ([M + Na]+ requires 982.1868). Rf = 0.37 (eluent
CHCl3/Me2CO, 40/1 v/v). IR νmax/cm−1 (KBr): 2933 m (C−H),
1630 s (CN). δH (300 MHz, CDCl3): 2.40 (3H, t, CH3 from p-tol),
7.20, 7.43, 7.55, 7.70, 7.82 (19H, 5 m, Haromatic). δC (75.5 MHz,
CDCl3): 10.1 (CH3 from p-tol), 98.3 (N−C−N), 121.1, 124.6, 127.5,
129.0, 129.5, 132.3, 133.2, 135.1, and 141.1 (Caromatic), 162.2 (C(O)
N).
15: 67.4 mg, 73%. Anal. Found: C, 64.92; H, 4.90; N, 7.59. Calcd
for C50H45N5Cl2O2Pd: C, 64.91; H, 4.90; N, 7.57. High-resolution
ESI+: m/z 949.1979 ([M + Na]+ requires 949.1977). Rf = 0.50 (eluent
CHCl3/Me2CO, 40/1 v/v). IR νmax/cm−1 (KBr): 2930 m (C−H),
1651 s (CN). δH (300 MHz, CD2Cl2): 2.21 (6H, s, CH3 from
C6H4Me-p of 5-NMe2-2,3-dihydro-1,2,4-oxadiazole ligand), 3.06 (3H,
s, CH3 from C6H4Me-p 5-Ph-2,3-dihydro-1,2,4-oxadiazole ligand),
3.06 (6H, br s, NMe2), 6.40, 6.79, 7.20, 7.43, 7.55, 7.70, 7.82 (33H, 7
m, Haromatic). δC (75.5 MHz, CDCl3): 21.5 (CH3 from C6H4Me-p),
2.40 (3H, t, CH3 from p-tol), 39.9 (NMe2), 98.5 and 98.3 (N−C−N),
121.1, 122.3, 125.0, 128.2, 128.9, 132.4, 135.8, 138.2, and 141.8
(Caromatic), 162.0 and 162.3 (C(O)N).
10b: 82.8 mg, 92%. Anal. Found: C, 58.50; H, 4.26; N, 6.21. Calcd
for C44H38N4Cl4O2Pd: C, 58.52; H, 4.24; N, 6.20. High-resolution
ESI+: m/z 926.0774 ([M + Na]+ requires 0926.0776). Rf = 0.42
(eluent CHCl3/Me2CO, 40/1 v/v). IR νmax/cm−1 (KBr): 2934 m (C−
H), 1637 s (CN). δH (300 MHz, CDCl3): 1.30 (3H, t, J = 7.6 Hz,
CH3 from Et), 2.82 (2H, q, J = 7.6 Hz, CH2 from Et), 6.49 (2H, d, o-
protons from C6H4Cl-p), 6.88 (2H, d, m-protons from C6H4Cl-p),
7.32, and 7.50 (10H, 2 m, Haromatic). δC (75.5 MHz, CDCl3): 9.9 (CH3
from Et), 22.6 (CH2 from Et), 98.4 (N−C−N), 123.3, 127.2, 128.3,
131.5, 132.7, 137.8, and 142.9 (Caromatic), 160.1 (C(O)N).
11b: 85.6 mg, 92%. Anal. Found: C, 56.60; H, 4.34; N, 9.02. Calcd
for C44H40N6Cl4O2Pd: C, 56.64; H, 4.32; N, 9.01. High-resolution
ESI+: m/z 934.1177 ([M + H]+ requires 934.1177). Rf = 0.42 (eluent
CHCl3/Me2CO, 40/1 v/v). IR νmax/cm−1 (KBr): 2928 m (C−H),
1666 s (CN). δH (300 MHz, CDCl3): 3.05 (6H, br s, NMe2), 6.40
(2H, d, o-protons from C6H4Cl-p), 6.94 (2H, d, m-protons from
C6H4Cl-p), 7.29, and 7.43 (10H, 2 m, Haromatic). δC (75.5 MHz,
CDCl3): 39.9 (NMe2), 98.6 (N−C−N), 123.1, 127.2, 128.5, 128.9,
132.5, 137.8, and 142.7 (Caromatic), 166.8 (C(O)N).
Liberation of 2,3-Dihydro-1,2,4-oxadiazole Ligands. dppe (2
equiv) was added to a solution of 7b−13b in CH2Cl2, and the reaction
mixture was stirred at room temperature for 4 h, whereupon the
15
colorless [Pd(dppe)2](Cl)2 precipitated. The dichloromethane
solutions of free 2,3-dihydro-1,2,4-oxadiazoles were filtrated off, and
the solvent was evaporated in vacuo at room temperature to give oily
residues of free heterocycles. Yields were almost quantitative.
Characterization of Metal-Free 2,3-Dihydro-1,2,4-oxadiazoles.
9c. High-resolution ESI+: m/z 392.1881 ([M + H]+ requires
392.1883). Rf = 0.43 (eluent CHCl3/Me2CO, 50/1 v/v). δH (300
MHz, CDCl3): 2.40 (3H, t, CH3 from p-tol), 7.19, 7.43, 7.53, 7.70,
7.80 (19H, 5 m, Haromatic). δC (75.5 MHz, CDCl3): 10.1 (CH3 from p-
tol), 98.1 (N−C−N), 121.0, 124.6, 127.5, 129.0, 129.4, 132.1, 133.2,
135.1, and 141.0 (Caromatic), 162.1 (C(O)N).
10c. High-resolution ESI+: m/z 386.1159 ([M + Na]+ requires
386.1156). Rf = 0.44 (eluent CHCl3/Me2CO, 50/1, v/v). δH (300
MHz, CDCl3): 1.30 (3H, t, J = 7.6 Hz, CH3 from Et), 2.80 (2H, q, J =
7.6 Hz, CH2 from Et), 6.49 (2H, d, o-protons from C6H4Cl-p), 6.87
(2H, d, m-protons from C6H4Cl-p), 7.32, and 7.50 (10H, 2 m,
Haromatic). δC (75.5 MHz, CDCl3): 9.9 (CH3 from Et), 22.5 (CH2 from
Et), 98.1 (N−C−N), 123.3, 127.1, 128.3, 131.5, 132.5, 137.8, and
142.8 (Caromatic), 160.1 (C(O)N).
12b: 80.9 mg, 81%. Anal. Found: C, 62.49; H, 3.83; N, 5.63. Calcd
for C52H38N4Cl4O2Pd: C, 62.51; H, 3.83; N, 5.61. High-resolution
ESI+: m/z 1022.0775 ([M + Na]+ requires 1022.0776). Rf = 0.41
(eluent CHCl3/Me2CO, 40/1 v/v). IR νmax/cm−1 (KBr): 2933 m (C−
H), 1630 s (CN). δH (300 MHz, CDCl3): 7.19, 7.43, 7.56, 7.72,
7.83 (5 m, Haromatic). δC (75.5 MHz, CDCl3): 98.3 (N−C−N), 121.0,
124.5, 127.5, 129.2, 132.3, 133.2, 135.1, and 141.2 (Caromatic), 162.2
(C(O)N).
11c. High-resolution ESI+: m/z 379.1440 ([M + H]+ requires
379.1446). δH (300 MHz, CDCl3): 3.01 (12H, br s, NMe2), 6.40 (2H
d, o-protons from C6H4Cl-p), 6.93 (2H, d, m-protons from C6H4Cl-p),
7.29, and 7.41 (10H, 2 m, Haromatic). δC (75.5 MHz, CDCl3): 39.8
(NMe2), 98.2 (N−C−N), 123.1, 127.2, 128.7, 128.9, 132.6, 137.6, and
142.7 (Caromatic), 166.7 (C(O)N).
13b: 44.2 mg, 91%. Anal. Found: C, 46.81; H, 5.53; N, 13.65. Calcd
for C24H34N6Cl2O2Pd: C, 46.80; H, 5.56; N, 13.65. High-resolution
ESI+: m/z 618.1328 ([M + H]+ requires 618.1327). Rf = 0.40 (eluent
12c. High-resolution ESI+: m/z 412.1335 ([M + H]+ requires
412.1337). Rf = 0.41 (eluent CHCl3/Me2CO, 50/1, v/v). δH (300
G
dx.doi.org/10.1021/ic301866y | Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
MHz, CDCl3): 7.18, 7.40, 7.56, 7.71, 7.82 (5 m, Haromatic). δC (75.5
MHz, CDCl3): 97.2 (N−C−N), 121.0, 124.3, 127.5, 129.1, 132.2,
133.1, 135.1, and 141.2 (Caromatic), 162.1 (C(O)N).
F. M.; Tung, T. Q.; Molchanov, A. P.; Kukushkin, V. Yu.
Organometallics 2012, 31 (2), 687−699.
(6) (a) Wagner, G.; Haukka, M. Dalton Trans. 2001, 18, 2690−2697.
(b) Wagner, G.; Pombeiro, A. J. L.; Kukushkin, V. Y. J. Am. Chem. Soc.
2000, 122 (13), 3106−3111. (c) Desai, B.; Danks, T. N.; Wagner, G.
Dalton Trans. 2003, 2544. (d) Desai, B.; Danks, T. N.; Wagner, G.
Dalton Trans. 2004, 166−171.
ASSOCIATED CONTENT
* Supporting Information
■
S
Tables, a figure, and a CIF file giving crystallographic data for
7b. This material is available free of charge via the Internet at
http://pubs.acs.org.
(7) (a) Lasri, J.; Charmier, M. A. J.; Haukka, M.; Pombeiro, A. J. L. J.
Org. Chem. 2007, 72 (3), 750−755. (b) Lasri, J.; Guedes da Silva, M.
F. C.; Kopylovich, M. N.; Mukhopadhyay, S.; Charmier, M. A. J.;
Pombeiro, A. J. L. Dalton Trans. 2009, 12, 2210−2216. (c) Lasri, J.;
Kopylovich, M. N.; Guedes da Silva, M. F. C.; Charmier, M. A. J.;
Pombeiro, A. J. L. Chem. Eur. J. 2008, 14 (30), 9312−9322.
(d) Charmier, M. A. J.; Kukushkin, V. Yu.; Pombeiro, A. J. L. Dalton
Trans. 2003, 2540−2543.
(8) (a) Beccalli, E. M.; Broggini, G.; La Rosa, C.; Passarella, D.; Pilati,
T.; Terraneo, A.; Zecchi, G. J. Org. Chem. 2000, 65, 8924−8932.
(b) Cordero, F. M.; Gensini, M.; Goti, A.; Brandi, A. Org. Lett. 2000, 2,
2475−2477. (c) Carmona, D.; Lamata, M. P.; Viguri, F.; Rodríguez, R.;
Oro, L. A.; Balana, A. I.; Lahoz, F. J.; Tejero, T.; Merino, P.; Franco, S.;
Montesa, I. J. Am. Chem. Soc. 2004, 126, 2716−2717. (d) Tamura, O.;
Mita, N.; Okabe, T.; Yamaguchi, T.; Fukushima, C.; Yamashita, M.;
Morita, Y.; Morita, N.; Ishibashi, H.; Sakamoto, M. J. Org. Chem. 2001,
66, 2602−2610. (e) Aggarwal, V. K.; Roseblade, S. J.; Barrell, J. K.;
Alexander, R. Org. Lett. 2002, 4, 1227−1229. (f) Zhao, Q.; Han, F.;
Romero, D. L. J. Org. Chem. 2002, 67, 3317−3322.
(9) (a) Bokach, N. A.; Kukushkin, V. Y. Russ. Chem. Rev. 2005, 74
(2), 153−170. (b) Bokach, N. A.; Kukushkin, V. Y.; Haukka, M.;
Pombeiro, A. J. L. Eur. J. Inorg. Chem. 2005, 5, 845−853.
(c) Kuznetsov, M. L.; Kukushkin, V. Y.; Pombeiro, A. J. L. Dalton
Trans. 2008, 10, 1312−1322. (d) Lasri, J.; Guedes da Silva, M. F. C.;
Kopylovich, M. N.; Mukhopadhyay, S.; Charmier, M. A. J.; Pombeiro,
A. J. L. Dalton Trans. 2009, 12, 2210−2216. (e) Wagner, G. Inorg.
Chim. Acta 2004, 357 (4), 1320−1324.
AUTHOR INFORMATION
Corresponding Author
■
*Fax: +7 812 4286733. Tel: +7 812 4286890. E-mail: bokach@
nb17701.spb.edu (N.A.B.); kukushkin@vk2100.spb.edu
(V.Y.K.).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Federal Targeted Program “Scientific and
Scientific-Pedagogical Personnel of the Innovative Russia in
2009−2013” (Contract No. P1294 from 09/06/2010) and
Russian Fund for Basic Research (Grant Nos. 11-03-00262 and
12-03-33071). We acknowledge St. Petersburg State University
for a research grant (2011−2013; No. 12.37.133.2011) and a
grant for applied research (2012−2013; No. 12.39.1050.2012).
A.S.K. expresses his gratitude to the Government of St.
Petersburg for a grant for graduate and undergraduate students
(2011). Prof. A. P. Molchanov and Dr. T.Q. Tung are thanked
for providing the ketonitrones for this study.
(10) Kuznetsov, M. L.; Kukushkin, V. Yu.; Pombeiro, A. J. L. J. Org.
Chem. 2010, 75, 1474−1490.
(11) Pombeiro, A. J. L. J. Organomet. Chem. 2005, 690 (24−25),
6021−6040.
(12) (a) Bertani, R.; Gotti, M.; Michelin, R. A.; Mozzon, M.; Bandoli,
G.; Angelici, R. J. Organometallics 1996, 15 (4), 1236−1241. (b) Leca,
F.; Lescop, C.; Toupet, L.; Reau, R. Organometallics 2004, 23 (26),
6191−6201.
(13) Liu, F. L.; Pullarkat, S. A.; Tan, K. W.; Li, Y. X.; Leung, P. H.
Organometallics 2009, 28, 6254.
REFERENCES
■
(1) Kukushkin, V. Yu.; Pombeiro, A. J. L Inorg. Chim. Acta 2005, 358
(1), 1−21.
(2) (a) Kukushkin, V. Yu.; Pombeiro, A. J. L. Chem. Rev. 2002, 102
(5), 1771−1802. (b) Bokach, N. A.; Kuznetsov, M. L.; Kukushkin, V.
Yu. Coord. Chem. Rev. 2011, 255, 2946−2967. (c) Kukushkin, V. Yu.;
Bokach, N. A. Russ. J. Gen. Chem. 2007, 77 (2), 194−205.
(3) (a) Michelin, R. A.; Mozzon, M.; Bertani, R. Coord. Chem. Rev.
1996, 147, 299−338. (b) Michelin, R. A.; Sgarbossa, P.; Sbovata, S.
M.; Gandin, V.; Marzano, C.; Bertani, R. ChemMedChem 2011, 6 (7),
1172−1183. (c) Ahmed, T. J.; Knapp, S. M. M.; Tyler, D. R. Coord.
Chem. Rev. 2011, 255 (7−8), 949−974. (d) Hvastijova, M.; Kohout, J.;
Buchler, J. W.; Boca, R.; Kozisek, J.; Jager, L. Coord. Chem. Rev. 1998,
175, 17−42. (e) Eglin, J. L. Comments Inorg. Chem. 2002, 23 (1), 23−
43. (f) Tfouni, E.; Ferreira, K. Q.; Doro, F. G.; da Silva, R. S.; da
Rocha, Z. N. Coord. Chem. Rev. 2005, 249 (3−4), 405−418.
(4) (a) Kissane, M.; Maguire, A. R. Chem. Soc. Rev. 2010, 2, 845−883.
(b) Stanley, L. M.; Sibi, M. P. Chem. Rev. 2008, 108, 2887−2902.
(c) Broggini, G.; Molteni, G.; Terraneo, A.; Zecchi, G. Heterocycles
2003, 59 (2), 823−858. (d) Gallos, J. K.; Koumbis, A. E. Curr. Org.
(14) Wagner, G. Chem. Eur. J. 2003, 9 (7), 1503−1510.
(15) Kojima, T.; Saeki, K.; Ono, K.; Ohba, M.; Matsuda, Y. Chem.
Commun. 1998, 4, 521−521.
(16) Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.; Orpen,
A. G.; Taylor, R. J. Chem. Soc., Perkin Trans. 2 1987, No. 12, S1−S19.
(17) (a) Sustmann, R. Tetrahedron Lett. 1971, 12 (29), 2717−2720.
(b) Sustmann, R. Tetrahedron Lett. 1971, 12 (29), 2721−2724.
(18) (a) Kuznetsov, M. L. Russ. Chem. Rev. 2006, 75 (11), 935−960.
(b) Kuznetsov, M. L.; Kukushkin, V. Yu. J. Org. Chem. 2006, 71 (2),
582−592. (c) Kuznetsov, M. L.; Kukushkin, V. Y.; Dement’ev, A. I.;
Pombeiro, A. J. L. J. Phys. Chem. A 2003, 107 (31), 6108−6120.
(d) Kuznetsov, M. L.; Kukushkin, V. Y.; Pombeiro, A. J. L. J. Org.
Chem. 2010, 75 (5), 1474−1490. (e) Himo, F.; Demko, Z. P.;
Noodleman, L.; Sharpless, K. B. J. Am. Chem. Soc. 2003, 125 (33),
9983−9987.
Chem. 2003, 7 (5), 397−425. (e) Karlsson, S.; Hogberg, H.-E. Org.
̈
Prep. Proced. Int. 2001, 33, 103.
(5) (a) Bokach, N. A.; Kuznetsov, M. L.; Haukka, M.; Ovcharenko,
V. I.; Tretyakov, E. V.; Kukushkin, V. Yu. Organometallics 2009, 28 (5),
1406−1413. (b) Bokach, N. A.; Krokhin, A. A.; Nazarov, A. A.;
Kukushkin, V. Yu.; Haukka, M.; Frausto Da Silva, J. J. R.; Pombeiro, A.
J. L. Eur. J. Inorg. Chem. 2005, 15, 3042−3048. (c) Makarycheva-
Mikhailova, A. V.; Golenetskaya, J. A.; Bokach, N. A.; Balova, I. A.;
Haukka, M.; Kukushkin, V. Yu. Inorg. Chem. 2007, 46 (20), 8323−
8331. (d) Bokach, N. A.; Ioffe, S. L.; Dolgushin, F. M.; Antipin, M. Y.;
Tartakovskii, V. A.; Kukushkin, V. Yu. Inorg. Chem. Commun. 2009, 12
(2), 173−176. (e) Kritchenkov, A. S.; Bokach, N. A.; Haukka, M.;
Kukushkin, V. Y. Dalton Trans. 2011, 40 (16), 4175−4182.
(f) Kritchenkov, A. S.; Bokach, N. A.; Kuznetsov, M. L.; Dolgushin,
(19) Erxleben, A.; Mutikainen, I.; Lippert, B. J. Chem. Soc., Dalton
Trans. 1994, 24, 3667−3675.
(20) (a) Svensson, P.; Lovqvist, K.; Kukushkin, V. Y.; Oskarsson, A.
Acta Chem. Scand. 1995, 49 (1), 72−75. (b) Bokach, N. A.;
Pakhomova, T. B.; Kukushkin, V. Y.; Haukka, M.; Pombeiro, A. J. L.
Inorg. Chem. 2003, 42 (23), 7560−7568.
(21) Johnson, A. W. J. Org. Chem. 1963, 28 (1), 252−254.
(22) Beckmann, E. Liebigs Ann. Chem. 1909, 365, 201−214.
(23) APEX2-Software Suite for Crystallographic Programs; Bruker AXS,
Inc., Madison, WI, 2009.
H
dx.doi.org/10.1021/ic301866y | Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
(24) Altomare, A.; Cascarano, G.; Giacovazzo, C.; Gualardi, A. J.
Appl. Crystallogr. 1993, 26 (3), 343−350.
(25) Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837−838.
(26) Sheldrick, G. M. SADABS-Bruker AXS Scaling and Absorption
Correction; Bruker AXS, Inc., Madison, WI, 2008.
(27) Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112−122.
I
dx.doi.org/10.1021/ic301866y | Inorg. Chem. XXXX, XXX, XXX−XXX