Metal-free and PdII-promoted [2+3] cycloadditions of a cyclic nitrone to phthalonitriles: Syntheses of oxadiazolines as well as phthalamide-PdII and dihydropyrrolyl-iminoisoindolinone-Pd II complexes with high catalytic activity in suzuki-miyaura cross-coupling reactions

Article abstract of DOI:10.1002/chem.200800510

The previously unknown reactions between phthalonitriles, 1,2-(CN) ₂(C₆)R¹R²R³R⁴ 1 (1a, R¹ = R² = R³ = R⁴ = H; 1b, R¹ = R² = R⁴ = H, R³ = CH ₃; 1e, R¹ = R⁴ = H, R² = R ³ = Cl; 1d, R¹ = R² = R³ = R ⁴ = Cl; 1e, R¹ = R² = R³ = R ⁴ = F), and a cyclic nitrone, ^-O⁺ N=CHCH ₂CH₂CMe₂ 2, proceed under heating in a sealed tube to give phthalimides 3, 2-oxadiazolyl-benzonitriles 4 or ortho-bis(oxadiazolyl)tetrafluorobenzene 4e′. In the presence of palladium(II) chloride, phthalonitriles 1 react with 2 at room temperature, to give bis(pyrrolidin-2-ylidene)phthalamide Pd^II complexes 5 via metal-promoted rupture of the N-O bond of the oxadiazoline ring. The ketoimine ligands thus generated can be liberated from the metal by displacement with a diphosphine. Although the first [2+3] cycloaddition of 2 to 1 can occur in the absence of the metal to give the monocycloadducts 4, the second [2+3] coupling at the still-unreacted cyano group requires its activation by coordination to Pdc, affording complexes 6 containing two ligated oxadiazolyl-benzonitriles. These ligands undergo either i) further cycloaddition with 2 to afford ultimately (upon rearrangement) the bis(pyrrolidinylidene)phthalamide complexes 5 or ii) N-O bond cleavage in the oxadiazoline ring with intramolecular attack of the imine nitrogen on the cyano carbon and bridging to a second Pd ^II center to afford dimeric palladium(II) complexes 7, with chloride bridges, that bear a dihydropyrrolyl-iminoisoindolinone, a new type of ligand. The compounds were characterized by IR, ¹H, and ¹³C NMR spectroscopy, ESI MS or FAB⁺ MS, elemental analyses and, in the case of 4c, 5 a, 5c, and 7c, also by X-ray diffraction analysis. Complexes 5a and 7c show high catalytic activity for the Suzuki-Miyaura cross-coupling reaction of bromobenzene and phenylboronic acid and give biphenyl in high yields with turnover frequencies (TOFs) of up to 9.0 × 10⁵ h^-1.

Full text of DOI:10.1002/chem.200800510

DOI: 10.1002/chem.200800510
Metal-Free and PdII-Promoted [2+3] Cycloadditions of a Cyclic Nitrone to
Phthalonitriles: Syntheses of Oxadiazolines as well as Phthalamide–PdII and
Dihydropyrrolyl-iminoisoindolinone–PdII Complexes with High Catalytic
Activity in Suzuki–Miyaura Cross-Coupling Reactions
Jamal Lasri,[a] Maximilian N. Kopylovich,[a] M. Fµtima C. Guedes da Silva,[a, b]
M. Adília Januµrio Charmier,[a, b] and Armando J. L. Pombeiro*[a]
Abstract: The previously unknown re-
actions between phthalonitriles, 1,2-
(CN)2(C6)R1R2R3R4 1 (1a, R1 =R2 =
R3 =R4 =H; 1b, R1 =R2 =R4 =H, R3 =
CH3; 1c, R1 =R4 =H, R2 =R3 =Cl; 1d,
R1 =R2 =R3 =R4 =Cl; 1e, R1 =R2 =
R3 =R4 =F), and a cyclic nitrone, ꢀO+
N=CHCH2CH2CMe2 2, proceed under
heating in a sealed tube to give phthal-
diphosphine. Although the first [2+3]
cycloaddition of 2 to 1 can occur in the
absence of the metal to give the mono-
cycloadducts 4, the second [2+3] cou-
pling at the still-unreacted cyano group
requires its activation by coordination
to PdII, affording complexes 6 contain-
ing two ligated oxadiazolyl-benzo-
the cyano carbon and bridging to a
second PdII center to afford dimeric
palladium(II) complexes 7, with chlo-
ride bridges, that bear a dihydropyrrol-
yl-iminoisoindolinone, a new type of
ligand.
The compounds were characterized
1
by IR, H, and 13C NMR spectroscopy,
A
ESI MS or FAB+ MS, elemental analy-
ses and, in the case of 4c, 5a, 5c, and
7c, also by X-ray diffraction analysis.
Complexes 5a and 7c show high cata-
lytic activity for the Suzuki–Miyaura
cross-coupling reaction of bromoben-
zene and phenylboronic acid and give
biphenyl in high yields with turnover
frequencies (TOFs) of up to 9.0”
105 hꢀ1.
A
further cycloaddition with 2 to afford
ultimately (upon rearrangement) the
bis(pyrrolidinylidene)phthalamide
ꢀ
1
complexes 5 or ii) N O bond cleavage
in the oxadiazoline ring with intramo-
lecular attackof the imine nitrogen on
give
bis(pyrrolidin-2-ylidene)phthal-
ACHTREUNG
amide PdII complexes 5 via metal-pro-
ꢀ
moted rupture of the N O bond of the
oxadiazoline ring. The ketoimine li-
gands thus generated can be liberated
from the metal by displacement with a
Keywords: heterocycles
· iminoi-
soindolinones · palladium · phthalo-
nitriles · Suzuki–Miyaura reaction
Introduction
Heterocycles have long been a research area of great inter-
est, owing in part to their catalytic[1] and biomedical[2] appli-
cations. They are of widespread occurrence in nature, for ex-
ample, in alkaloids. In this area, although derivatives of the
lactam or oxadiazoline rings have applications as antitumor
agents or as antibiotics,[3] those containing indole or isoin-
dole ring systems are important intermediates in the synthe-
sis of phthalocyanins.[4,5] Aromatic heterocyclic compounds
also find applications based on their photochemical proper-
ties or as luminescent molecular sensors, and in supramolec-
ular (polynuclear) complexes with interesting optical or
magnetic properties.[6] On the other hand, because pallad-
[a] Dr. J. Lasri, Dr. M. N. Kopylovich, Dr. M. F. C. Guedes da Silva,
Dr. M. A. J. Charmier, Prof. Dr. A. J. L. Pombeiro
Centro de Química Estrutural, Complexo I
Instituto Superior TØcnico, TU Lisbon
Av. Rovisco Pais, 1049–001 Lisbon (Portugal)
Fax : (+351)218-464-455
E-mail: pombeiro@ist.utl.pt
[b] Dr. M. F. C. Guedes da Silva, Dr. M. A. J. Charmier
Universidade Lusófona de Humanidades e Tecnologias
ULHT Lisbon, Av. Campo Grande no 376
1749–024, Lisbon (Portugal)
9312
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 9312 – 9322

FULL PAPER
A
lated with an important class of heterocyclic compounds
with promising biological activity.[13] Finally, by this process,
we synthesized a novel type of dimeric palladium complex
(aim 4) with the 2-dihydropyrrolyl-iminoisoindolinone
ligand, which, to our knowledge, is the first example of such
a type of compound reported to date.
synthetically useful catalytic reactions,[7] the combination of
palladium with heterocyclic ligands is expected to lead to
new active species.
1) To find new types of synthetic reactions for heterocyclic
compounds.
2) To synthesize novel heterocycles.
Concerning aim 5 (the search for a catalytic application),
we have focused our attention on the Suzuki–Miyaura reac-
tion,[14] one of the most powerful C–C cross-coupling reac-
tions, which is known to be catalyzed by some PdII com-
plexes, which contain N ligands. We have thus found that
representatives of our mono- and dinuclear complexes act
as very active catalysts for the cross-coupling reaction of
bromobenzene and phenylboronic acid to give biphenyl in
high yield with a turnover frequency (TOF) reaching 9.0”
105 hꢀ1.
3) To study the influence of palladium(II) in such reactions.
4) To prepare novel types of palladium(II) complexes with
heterocyclic ligands.
5) To find a catalytic application of such PdII complexes in
a recognized important synthetic reaction.
With aims 1–4 in mind, we have selected 1,3-dipolar cy-
cloaddition reactions, which constitute a powerful tool to
ꢀ
ꢀ
create C N and C O bonds, for the synthesis of a great va-
riety of heterocycles.[8] However, one of the main problems
of cycloadditions is that various dipolarophiles, such as orga-
nonitriles, do not commonly undergo 1,3-dipolar cycloaddi-
tions due to their low reactivity.[9] Second, a heterocycle syn-
thesis often consists of sequential reactions that can involve
one or more thermodynamically unfavourable steps. To
overcome such difficulties, alternative metal-mediated cyclo-
additions have been the object of extensive current investi-
gations due to the possible key role of a metal for their pro-
motion.[9]
Results and Discussion
Organic reactions: Because, to our knowledge, the reactivity
of nitrones toward phthalonitriles has not yet been reported,
in spite of its potential synthetic value, we decided to study
the reactions of the cyclic nitrone ꢀO+ N=CHCH2CH2CMe2
2 with various phthalonitriles 1,2-(CN)2(C6)R1R2R3R4 1, by
heating their CHCl3 solutions in a sealed tube at 808C. The
resulting products, isolated by column chromatography on
silica (CH2Cl2 as eluent), depend on the nature of the sub-
stituents in the starting phthalonitriles 1. Hence, the reac-
tions of 1a (R1 =R2 =R3 =R4 =H) and its methyl derivative
1b (R1 =R2 =R4 =H, R3 =CH3) with the cyclic nitrone 2,
under the above conditions, give the phthalimide 3a and the
5-methyl derivative 3b, respectively, in moderate yields (ca.
50%) (Scheme 1). No reaction was observed at room tem-
perature or under refluxing CHCl3 at ambient pressure.
The formation of 3 can be proposed (Scheme 2) to occur
by hydrolysis of the nitrone (a known reaction[15]) to give
the corresponding a-hydroxy hydroxylamine (i.e. 5,5-dime-
thylpyrrolidine-1,2-diol) I which would react with the phtha-
lonitrile in a comparable way to that reported[16] for the hy-
droxylamine Et2NOH, that is, by nucleophilic addition to a
CN group with CN–CN coupling to give an imino species II.
Further transformation with liberation of 5,5-dimethyl-3,4-
dihydropyrrol-2-ol III would form the 3-iminoisoindolin-1-
one IV, which, upon hydrolysis, would furnish[17] the phthali-
mide product 3.
As a continuation of our project on 1,3-dipolar cycloaddi-
tion reactions of free and metal-activated organonitriles
with various dipoles, for example, nitrones,[10–12] we have
now extended the work, for the first time, to phthalonitriles
(substituted 1,2-dicyanobenzenes). Our objective (within the
above aims 1–4) is to study the previously unknown [2+3]
cycloaddition reactions of cyclic and acyclic nitrones with
these aromatic dinitriles in pure organic chemistry, to syn-
thesize novel N-heterocycles, and to investigate the effect of
a coordinating PdII center on such reactions.
One or both of the cyano groups of a phthalonitrile can
react, in the latter case in similar or different ways, allowing
the formation of a variety of products, namely phthalimides
and fused mono- and bis-oxadiazolines, attached to the
phenyl ring of the phthalonitrile precursor, depending on
electronic effects of the substituents at this ring.
Unpredictable results were obtained when the reactions
were undertaken in the presence of palladium(II) chloride
(aim 3) giving rise to unexpect-
ed substituted bis(pyrrolidin-2-
ylidene)phthalamide-PdII com-
plexes (aim 4) which, by subse-
quent ligand replacement, al-
lowed the liberation of the cor-
responding novel free phthal-
ACHTREUNG
amides, for example, N1,N2-
bis(5,5-dimethylpyrrolidin-2-yli-
dene)-3,4,5,6-tetrafluorophtha-
lamide (aim 2), structurally re- Scheme 1. Synthesis of phthalimides from phthalonitriles and cyclic nitrone.
Chem. Eur. J. 2008, 14, 9312 – 9322
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9313

A. J. L. Pombeiro et al.
lents of the nitrone 2 and under
more drastic conditions (pro-
longed heating and/or higher
concentrations of the reagents
in the CHCl3 solution) than
those normally used, the forma-
tion of mixtures with com-
pounds (5–2% yields) derived
from [2+3] cycloadditions to
1
both nitriles was detected by H
and 13C NMR spectroscopy and
FAB MS.
The phthalimides 3 and the
2-(oxadiazolyl)-benzonitrile
products 4c–e were character-
ized by IR, 1H and 13C NMR
spectroscopy, FAB+ MS, ele-
mental analyses and, for 4c, by
single-crystal X-ray diffraction.
In the IR spectra of compounds
ꢁ
4, nACHTRE(UNG N C) appears in the same
range of wavenumbers (2234–
2242 cmꢀ1) as that observed for
the starting phthalonitriles 1c–
1e, whereas the detection of
new bands at 1628–1680 cmꢀ1
assigned to nACHTER(UNG N=C) confirms
the formation of the oxadiazo-
line; additionally, the detection
of nACHTER(UNG NC=O) vibrations at 1735–
1742 cmꢀ1 can be accounted for
by the appropriate tautomeric
resonance forms of the oxadia-
Scheme 2. Proposed mechanism of phthalimide synthesis.
1
In contrast, the reactions of the phthalonitriles 1c–e con-
taining an electron-withdrawing group (1c, R1 =R4 =H,
R2 =R3 =Cl; 1d, R1 =R2 =R3 =R4 =Cl; 1e, R1 =R2 =R3 =
R4 =F) with one or two equivalents of cyclic nitrone 2,
under the above experimental conditions (sealed tube,
808C, CHCl3) afford, in moderate to good yields (70–35%),
the 2-(oxadiazolyl)-benzonitrile
zoline ring. The H and 13C NMR spectra of 4 confirm that
the compounds contain both an oxadiazoline and a nitrile
ꢀ
ꢀ
moiety. In the former spectrum, the N CH N resonances
are detected at d=5.75–5.85 ppm, and, in the latter spec-
ꢀ
ꢀ
trum, the N CH N resonances appear at d=91.7–92.5 ppm,
whereas the N C signals are observed in the d=109.3–
ꢁ
derivatives 4c–4e, derived from
a single-pot [2+3] cycloaddition
reaction of the nitrone 2 to the
phthalonitriles
1c–1e
(Scheme 3), a known[18] type of
nitrile and nitrone coupling. It
is worth mentioning that the at-
tempts to obtain similar prod-
ucts by using the acyclic nitrone
(4-MeC6H4)CH=(Me)N+Oꢀ, in-
stead of the more reactive
cyclic one, failed and led to the
formation of oily mixtures of
unidentified products.
When the reactions of the
phthalonitriles 1c and 1d were
undertaken with two equiva- Scheme 3. Synthesis of 2-(oxadiazolyl)benzonitrile derivatives 4c–4e.
9314
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 9312 – 9322

ACHTREUNG[2+3] Cycloadditions of a Cyclic Nitrone to Phthalonitriles
FULL PAPER
cloaddition with the cyclic nitrone 2, converting into the
symmetrical ortho-bis(oxadiazolyl)tetrafluorobenzene 4e’.
The IR spectrum of 4e’ does not exhibit any band that
ꢁ
could be assigned to nACHTRE(UGN N C) and the NMR data also prove
ꢀ
that the compound was isolated without ring-opening by N
O bond rupture of the oxadiazoline ring, in contrast to what
we have recently observed[12] in other cases.
Inorganic template synthesis: In this second part of the
work, we investigated the reactions of the phthalonitriles
with the cyclic nitrone in the presence of palladium chloride
(PdCl2), thus comparing the reactivity with that in the ab-
sence of this metal site and investigating the PdII-activating
(and templating) effect.
Figure 1. Molecular structure of 4,5-dichloro-2-(5,5-dimethyl-5,6,7,7a-tet-
rahydroazolo[1,2-b,1,2,4]oxadiazol-2-yl)benzonitrile 4c with atomic num-
Treatment of the phthalonitriles 1 with two equivalents of
the cyclic nitrone 2 and one equivalent of PdCl2 in acetone
at room temperature for 12 h gave the corresponding bis(-
pyrrolidin-2-ylidene)phthalamide PdII complexes 5 in good
yields (73–90%) (Scheme 5). Elemental analyses, FAB+
ꢀ
bering scheme. Selected bond lengths [Š] and angles [8]: Cl5 C5
ꢀ
ꢀ
ꢀ
ꢀ
1.729(3), O1 N4 1.493(3), O1 C1 1.358(3), N1 C1 1.260(4), N1 C10
ꢀ
ꢀ
ꢀ
ꢀ
1.472(3), N2 C2 1.147(5), N4 C10 1.511(4), N4 C13 1.504(4), C1 C3
ꢀ
ꢀ
ꢀ
1.482(4), C2 C8 1.449(4), C3 C4 1.382(4), C10 C11 1.542(4); N4-O1-C1
105.05(18), C1-N1-C10 106.2(2), O1-N4-C10 101.83(17), N4-C13-C132
111.7(2), O1-N4-C13 106.88(19), O1-C1-N1 118.6(2), O1-C1-C3 115.6(2),
N1-C1-C3 125.8(2), N2-C2-C8 173.6(3), N1-C10-C11 111.5(2).
1
MS, IR, H, and 13C NMR spectra, and X-ray data (for 5a
and 5c) confirm the proposed formulas. For example, com-
parison of the IR spectra of these complexes with those of
ꢁ
the starting phthalonitriles shows that the C N stretching vi-
brations are replaced by the strong n
G
G
116.1 ppm range. The single-crystal X-ray diffraction analy-
sis of 4c (Figure 1) also confirms the formulation. The cyano
vibrations at approximately 1731 and 1633 cmꢀ1, respectively
and that the n(NH) band at 3237–3433 cmꢀ1 emerges. More-
over, the 13C NMR resonances at dꢂ169.0 and 173.9 ppm
are assigned to the N=CNH and NC=O moieties, respective-
ꢁ
C2 N2 triple bond length, 1.147(5) Š, and the imine double
bond C1=N1 length, 1.260(4) Š, are in accord with the re-
1
ported[19] average values of 1.144 and 1.279 Š, respectively.
ly. In the H NMR spectra, the NH resonances are detected
ꢀ
ꢀ
It can also be seen that the N1=C1 O1 double bond is delo-
at dꢂ10.7 ppm and confirm the N O ring cleavage.
calized, which is in accord with
the above IR data (bands at ca.
1740 cmꢀ1).
Curiously, the reaction of tet-
rafluorophthalonitrile 1e with
two equivalents of the nitrone 2
in a sealed tube (CHCl3, 808C)
for an extended period (16 h in-
stead of 3 h for the formation
of the monooxadiazoline 4e)
proceeds further to give the bis-
oxadiazoline 4e’, in moderated
yield (30%) (Scheme 4, reac-
tion 1). This product is also ob-
tained (Scheme 4, reaction 2)
by treatment of the mono-cy-
cloadduct 4e with one equiva-
lent of the nitrone 2 (CHCl3,
16 h, 808C). The formation of
4e’ from the reaction of 1e
with 2 is thus believed to pro-
ceed via the mono-cycloadduct
4e in which the cyano group,
activated by the four fluoro
substituents of the phenyl ring,
undergoes, after a prolonged re-
action time, a further [2+3] cy- Scheme 4. Synthesis of bisoxadiazoline 4e’ from 1) phlathonitrile 1e and 2) from oxadiazoline 4e.
Chem. Eur. J. 2008, 14, 9312 – 9322
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9315

A. J. L. Pombeiro et al.
ꢀ
ꢀ
similarity of N1 C11, N11 C11,
ꢀ
and N1 C1 bond lengths
(1.340, 1.320, and 1.395 Š, re-
spectively) shows a significant
delocalization of the N1=C11
double bond along the O1-C1-
N1-C11-N11 fragment with cor-
responding formation of the
enol form.[12]
However, the reaction of
phthalonitriles 1 with the less
reactive acyclic nitrone (4-
C6H4)=CH(Me)N+Oꢀ in the
presence of PdCl2, upon solvent
reflux for one day, results in the
formation of mixtures of un-
identified products.
Mechanistic investigations: At-
tempted reactions of the phtha-
Scheme 5. Synthesis of palladacycles 5.
lonitriles 1 with one equivalent
of PdCl2, in the absence of the
nitrone, at room temperature or in refluxing acetone for one
weekresulted in quantitative recovery of the starting mate-
rials. Hence, the formation of complexes 5 should not be
expected to occur via coordination of the phthalonitrile
to Pd.
Surprisingly, treatment of 4,5-dichloro-2-(oxadiazolyl)ben-
zonitrile 4c or tetrafluoro-2-(oxadiazolyl)benzonitrile 4e
with one equivalent of PdCl2 in acetone for 72 h at room
temperature gives the unusual dimers [{PdClACHTREUNG
N=C(R1R2R3R4C6)
A
ACHTREUNG
ꢀ ꢀ
ꢀ
ꢀ
7c (R1 =R4 =H, R2 =R3 =Cl) or 7e (R1 =R2 =R3 =R4 =F),
respectively, with the substituted iminoisoindolinone moiety
(Scheme 6). Compounds 7c and 7e were characterized by
conventional methods (see Experimental) and for 7c
(Figure 3) the structure was also authenticated by a single-
crystal X-ray diffraction analysis. The IR spectra show the
Figure 2. Partial stickrepresentation of the crystal packing diagram of
complex 5a with atomic numbering scheme (hydrogen atoms except of
H11 and H21 and solvent molecules are omitted for clarity). Selected
ꢀ
ꢀ
bond lengths [Š] and angles [8]: Pd1 Cl1 2.303(2), Pd1 N1 2.047(7),
ꢀ
ꢀ
ꢀ
ꢀ
O1 C1 1.227(10), N1 C11 1.340(14), N1 C1 1.395(10), N11 C11
ꢀ
ꢀ
conjugated N C=N and N C=O moieties at approximately
1680 and 1750 cmꢀ1, respectively. The 13C NMR spectra ex-
hibit typical C=N and C=O resonances at dꢂ160 and
164 ppm. The N1=C1, N3=C11, and C2=O1 bonds in 7c
ꢀ
ꢀ
ꢀ
1.320(12), N11 C14 1.488(14), C1 C8 1.493(15), C11 C12 1.500(12);
Cl1-Pd1-Cl2 91.87(9), Cl1-Pd1-N1 89.6(2), Cl1-Pd1-N2 174.9(2), C1-C8-
C7 117.9(8), N1-Pd1-N2 85.5(3), Pd1-N1-C1 118.5(7), N1-C11-N11
128.1(7), Pd1-N1-C11 120.3(5), N11-C11-C12 109.8(9), C11-N11-C14
114.0(7), O1-C1-N1 123.8(9), N1-C1-C8 115.9(7). Selected hydrogen
ꢀ
have a significant double-bond character, whereas C1 N2,
ꢀ
ꢀ
bonds: N11 H11···O1 2.11, N21 H21··O1 2.23.
ꢀ
ꢀ
C11 N2, and C2 N2 are mainly single bonds. Thus, in this
ꢀ
ꢀ
case, the p-electron delocalization in the N C=O and N C=
N moieties is much lower than in compounds 5. To our
knowledge, dimers 7 represent the first examples of metal
complexes with 2-dihydropyrrolyl-iminoisoindolinone li-
gands.
The structures of compounds 5a (Figure 2) and 5c were
also determined by single-crystal X-ray analysis. These two
compounds are quite similar so we will only discuss struc-
ture 5a in more detail. The molecular structure of 5a shows
two strong hydrogen bonds between the amine moieties of
the nitrone-derived heterocycle and the keto oxygen O1
atom, one is intramolecular (H11···O1 2.11 Š and N11
H11···O1 1218) and the other one intermolecular (H21···O1
2.2300 Š and N21 H21···O1 1448) (Figure 2b). The C1=O1
and the C2=O2 bond lengths, 1.227(10) and 1.218(10) Š, re-
From the mechanistic viewpoint, we believe that dimers 7
are formed via coordination of two molecules of 4 to palla-
dium chloride through the nitrile groups to yield the inter-
mediates 6 (Scheme 6). Subsequent opening of the oxadia-
zoline ring and spontaneous intramolecular attackof the
imine nitrogen on the cyano carbon which bridges to a
second palladium chloride, with elimination of HCl then
occurs (rearrangements partially shown as route a on the
ꢀ
ꢀ
ꢀ
spectively, within the N C=O moieties are in accord with
the average value, 1.225 Š,[19] for amide derivatives. The
9316
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 9312 – 9322

ACHTREUNG[2+3] Cycloadditions of a Cyclic Nitrone to Phthalonitriles
FULL PAPER
[PdCl2(organonitrile)2]
com-
plexes are not stable in solu-
tion, in our workthe isolation
of the complex 6c from the re-
action mixture was successful
and its structure was confirmed
by IR and NMR spectroscopy,
ESI MS, and elemental analysis
(see the Experimental Section).
Furthermore, the related inter-
mediate 6e was detected direct-
ly in the reaction mixture by
ESI MS. Refluxing acetone sol-
utions of complexes 6 for 48 h
leads to the formation of
dimers 7, confirming that com-
pounds 6 are precursors of 7.
The reactions of the 2-(oxa-
diazolyl)benzonitriles
4
with
one equivalent of the cyclic ni-
trone 2 and one equivalent of
PdCl2 in acetone at room tem-
perature for 12 h give exclusive-
ly the corresponding (pyrroli-
din-2-ylidene)phthalamide PdII
complexes 5 (Scheme 6). The
same products 5 are obtained
by treatment of the intermedi-
ates 6 with one equivalent of
the nitrone 2 in acetone for
12 h at room temperature. In
contrast, the dimers 7 do not
react with the cyclic nitrone 2
in acetone (room temperature,
72 h).
Attempts to prepare complex
5e by reaction of the ortho-bi-
s(oxadiazolyl)tetrafluoroben-
zene 4e’ (Scheme 4) with one
equivalent of palladium chlo-
ride have failed and only the
starting materials were recov-
ered quantitatively even after 4
days under solvent reflux, possi-
bly on account of the bulkiness
of the oxadiazoline moieties
that can hamper their coordina-
tion. This provides further sup-
port for the formation of com-
plexes 5 via the mono-cycload-
ducts 4.
Scheme 6. Proposed mechanism for the synthesis of palladacycles 5.
The above results show that
the intermolecular nucleophilic
attackof the cyclic nitrone 2 on the cyano carbon of 6
(Scheme 6, route b) to give complexes 5 occurs in prefer-
structural formula of 6, Scheme 6). We recently discovered
similar transformations involving nucleophiles such as
oximes and hydroxylamines.[16,20] Although previous re-
ꢀ
ence to the intramolecular rearrangement of 6 (via N O
ports[21]
indicate
that,
in
some
cases,
trans-
bond cleavage and nucleophilic attackof the imino moiety
Chem. Eur. J. 2008, 14, 9312 – 9322
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9317

A. J. L. Pombeiro et al.
ꢀ
this atom capable of abstracting the oxygen of the O N
group to form the ketoimino moiety N
A
rearrangement involving a formal 1,2-H shift from the CH
carbon of the oxadiazoline ring to the adjacent and deoxy-
genated N atom.
Liberation of ketoimine 5e’: The possibility of liberation of
the ketoimine ligand from a complex 5 is illustrated by dis-
placement with 1,2-bis(diphenylphosphanyl)ethane (dppe)
from 5e (Scheme 7). When precipitation of the colorless
(dppe)] (identified by IR and 31P NMR
compound, [PdCl2ACHTREUNG
spectroscopy[22]) was complete, the quantitative formation of
the free ketoimine 5e’ was confirmed by IR, 1H, and
13C NMR spectroscopy (see Experimental Section).
Catalysis: Because palladium(II) complexes with two N-co-
ordinated ligands are known[14] to act as catalysts for the
Suzuki–Miyaura cross-coupling reaction of bromobenzene
(PhBr) and phenylboronic acid (PhB(OH)2) to give biphen-
yl, we have also tested the possible catalytic applications of
representatives of our mono- and dinuclear PdII complexes
of types 5 and 7 in that reaction. We have thus observed
that complexes 5a and 7c show a very high catalytic activity
for the standard Suzuki–Miyaura system (1 equiv of bromo-
benzene and 1.2 equiv of phenylboronic acid) (Table 1).
High isolated yields of biphenyl (up to 97%) are achieved
in toluene at 1008C, with K2CO3 as a base, with turnover
numbers (TON) up to 9.3”105 and 9.5”105 moles of bi-
phenyl per mole of catalyst, and turnover frequencies
(TOF) of up to 1.8”105 and 9.0”105 moles of biphenyl per
mole of catalyst per hour, for 5a and 7c, respectively. These
results are amongst the best ones so far reported in the
field.[23]
Figure 3. Molecular structure view along the b axis of complex 7c with
atomic numbering scheme. Hydrogen atoms and solvent molecules are
ꢀ
omitted for clarity. Selected distances [Š] and angles [8]: Pd1 Pd1a
ꢀ
ꢀ
ꢀ
ꢀ
2.9380(8), Pd1 Cl1 2.3266(16), Pd1 N1 1.972(5), Pd1 N3 2.019(4), O1
ꢀ
ꢀ
ꢀ
ꢀ
C2 1.197(8), N1 C1 1.261(7), N2 C2 1.426(7), N2 C11 1.383(7), N2 C1
ꢀ
ꢀ
ꢀ
ꢀ
1.430(8), N3 C1 1.521(8), N3 C11 1.291(7), C1 C8 1.476(8), C2 C3
1.466(8); Cl1-Pd1-N3 100.69(14), Pd1a-Pd1-Cl1 125.64(4), Cl1-Pd1-N1a
91.31(13), N1-Pd1-N3 89.79(18), N1-C1-N2 123.6(5), C1-N2-C11 124.4(5),
C1-N2-C2 110.4(5), N2-C11-N3 124.6(5), C11-C12-C13 101.4(5), Pd1-N3-
C11 123.2(4), O1-C2-N2 125.7(5). Symmetry transformations used to gen-
erate the equivalent atoms: a) ꢀx, y, 1/2ꢀz.
to the cyano carbon, route a) that would lead to the forma-
tion of dimers 7. In contrast, reactions of 4 with other nucle-
ophiles such as the acyclic nitrone ꢀO+N(Me)=C(H)-
ACHTREUNG(C6H4Me-4), N,N-diethylhydroxylamine Et2NOH or acetone
oxime Me2C=NOH instead of the cyclic nitrone 2, under the
same experimental conditions, afford the dimers 7 as exclu-
sive products. In this case the intramolecular rearrangement
is more favourable than the intermolecular addition, in
accord with the lower reactivity of these nucleophiles in
comparison with the cyclic nitrone.
The intermolecular reaction (b, Scheme 6) leading to the
complexes 5 is believed to proceed via [2+3] cycloaddition
of the cyclic nitrone 2 to the
Conclusion
The results of this workshow that the purely organic reac-
tions between the phthalonitriles 1 and the cyclic nitrone 2
proceed under harsh conditions (heating in a sealed tube) to
give phthalimide 3, 2-(oxadiazolyl)benzonitrile 4, or ortho-
cyano moiety of one nitrile
ligand in 6 and elimination of
the other one to give an unsta-
ble bicyclic 1,2,4-oxadiazoline-
PdII intermediate 8 in which the
ꢀ
rupture of the N O bond is
promoted by the metal site. The
course of this type of reaction,
which proceeds through an oxa-
diazoline–Pt complex related to
8 was demonstrated by us in a
previous study.[12] The metal
center increases the oxophilic
character of the imine N=
C(R)ON carbon and renders Scheme 7. Liberation of ketoimine 5e’.
9318
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 9312 – 9322

ACHTREUNG[2+3] Cycloadditions of a Cyclic Nitrone to Phthalonitriles
FULL PAPER
Table 1. Catalytic activity of complexes 5a and 7c for the Suzuki–
substituted phthalonitriles, which provide access to novel
multifunctional heterocyclic oxadiazoline, phthalamide, and
iminoisoindolinone rings, with eventual significance for ap-
plications as dyes, pigments, or intermediates for the synthe-
ses of pharmaceutical and naturally occurring compounds.
The use of PdII complexes with such types of ligands as cata-
Miyaura cross-coupling reaction of bromobenzene and phenylboronic
acid.[a]
[d]
Entry Catalyst [mmol] t [h] Yield [%][b] TON[c]
TOF [hꢀ1
]
1
2
3
4
5
6
7
8
9
5a (5”10ꢀ4
5a (5”10ꢀ4
5a (5”10ꢀ5
5a (5”10ꢀ5
5a (5”10ꢀ5
5a (5”10ꢀ6
5a (5”10ꢀ6
)
)
)
)
)
)
)
24
1
24
1
97
95
94
92
9.7”103 4.1”102
9.5”103 9.5”103
9.4”104 3.9”103
9.2”104 9.2”104
9.0”104 1.8”105
9.3”105 3.9”104
9.0”105 1.3”105
9.7”103 4.1”102
9.4”104 3.9”103
9.5”105 3.2”105
9.0”105 9.0”105
ꢀ
lysts for C C coupling reactions was demonstrated for par-
ticular cases and the extension to other related catalytic re-
actions appears to be rather promising and deserves to be
explored.
0.5 90
24
7
24
24
3
93
90
97
94
95
90
7c (5”10ꢀ4
7c (5”10ꢀ5
7c (5”10ꢀ6
7c (5”10ꢀ6
)
)
)
)
10
11
1
Experimental Section
[a] PhBr (5.0 mmol) + PhB(OH)2 (6.0 mmol) + K2CO3 (10.0 mmol) +
catalyst toluene (50 mL), in air, at 1008C (see Experimental).
+
Material and instrumentation: Solvents and reagents were obtained from
commercial sources (Aldrich) and used as received. The acyclic nitrone
was synthesized by condensation of 4-methylbenzaldehyde and N-methyl-
hydroxylamine, according to a published method.[24] For TLC, Merck
Silica gel 60F254 plates have been used. C, H, and N elemental analyses
were carried out by the Microanalytical Service of the Instituto Superior
TØcnico. 1H and 13C spectra (in CDCl3, CDCl3/CD3OD or [D6]DMSO)
were measured on Bruker Avance II 300 and 400 MHz (UltraShield
Magnet) spectrometers at ambient temperature. 1H and 13C chemical
shifts (d) are expressed in ppm relative to SiMe4. J values are in Hz. In-
[b] Moles of biphenyl per 100 moles of PhBr. [c] Turnover number
(moles of biphenyl per mole of catalyst). [d] Turnover frequency (moles
of biphenyl per mole of catalyst per hour).
bis(oxadiazolyl)tetrafluorobenzene 4e’ derivatives, depend-
ing on the nature of substituents in the starting phthalo-
ACHTREUNGnitriles (an electron-withdrawing substituent, such as F, pro-
motes the [2+3] cycloaddition which can even occur at both
cyano groups in tetrafluorophthalonitrile) and on the reac-
tion time. In contrast, the reactions in the presence of a pal-
ladium(II) site proceed, under mild conditions, in a con-
trolled way, providing an easy and selective access to
frared spectra (4000–400 cmꢀ1
) were recorded on a Bio-Rad FTS
3000mX and a Jasco FTIR-430 instrument in KBr pellets and the wave-
numbers are in cmꢀ1. Positive-ion FAB mass spectra were obtained on a
Trio 2000 instrument by bombarding 3-nitrobenzyl alcohol (NBA) ma-
trixes of samples with 8 keV (ca. 1.28”1015 J) Xe atoms. Electrospray
mass spectra were carried out with an ion-trap instrument (Varian 500-
MS LC Ion Trap Mass Spectrometer) equipped with an electrospray
(ESI) ion source. For electrospray ionization, the drying gas and flow
rate were optimized according to the particular sample with 35 p.s.i. neb-
ulizer pressure. Scanning was performed from m/z 50 to 1500. The com-
pounds were observed in the positive mode (capillary voltage=80–
105 V).
bisACHTREUNG
(pyrrolidin-2-ylidene)phthalamide PdII complexes 5 via
an unprecedented single-pot reaction, in which the sponta-
ꢀ
neous rupture of the N O bond of the oxadiazoline ring is
promoted by the metal center. The ketoimine ligands thus
generated can be successfully liberated from the metal by
displacement with dppe.
Reactions of phthalonitriles 1 (1a, R1 =R2 =R3 =R4 =H; 1b, R1 =R2 =
R4 =H, R3 =CH3; 1c, R1 =R4 =H, R2 =R3 =Cl; 1d, R1 =R2 =R3 =R4 =
Cl; 1e, R1 =R2 =R3 =R4 =F) with the cyclic nitrone ꢀO+ N=
A first [2+3] cycloaddition of a phthalonitrile 1 with the
nitrone 2 can occur in the absence of the metal to give a
mono-cycloadduct (2-(oxadiazolyl)benzonitrile 4), but the
second [2+3] coupling at the still-unreacted cyano group re-
quires its activation by coordination to PdII, to afford a com-
plex 6 with two ligated oxadiazolyl-benzonitriles. These li-
gands show quite a versatile reactivity and can undergo
either i) further cycloaddition with the cyclic nitrone to
afford ultimately (upon rearrangement) the (pyrrolidinylide-
CHCH2CH2CMe2 2:
A solution of 1a (50.0 mg, 0.390 mmol), 1b
(50.0 mg, 0.352 mmol), 1c (50.0 mg, 0.254 mmol), 1d (50.0 mg,
0.188 mmol) or 1e (50.0 mg, 0.249 mmol) in CHCl3 (4 mL) was added at
room temperature to the nitrone 2 (2 equiv) and the mixture was heated
at 808C in a sealed stainless steel tube for 12 h (1a, 1c), 72 h (1b), 7 h
(1d) or 3 h (1e) and the progress of the reaction was monitored by TLC.
After evaporation of the solvent to dryness in vacuo, the crude residue
was purified by column chromatography on silica (CH2Cl2) followed by
evaporation of the solvent in vacuo to give the final products 3a, 3b, 4c,
4d, or 4e, respectively.
ꢀ
ne)phthalamide complexes 5 or ii) N O bond cleavage in
the oxadiazoline ring with spontaneous intramolecular
attackof the imine nitrogen on the cyano carbon and bridg-
ing to a second PdII center (upon HCl elimination) to afford
the final dimeric products 7. They bear a previously un-
known type of ligand, that is, a dihydropyrrolyl-iminoisoin-
dolinone, and represent the first examples of complexes
with such a ligand. The obtained PdII complexes 5 and 7
with the N-coordinated (pyrrolidinylidene)phthalamide and
dihydropyrrolyl-iminoisoindolinone ligands, respectively,
possess a remarkably high catalytic activity toward the
Suzuki–Miyaura cross-coupling reaction, achieving the TOF
value of 9”105 hꢀ1.
Compound 3a: Yield: 49%; 1H NMR (300 MHz, CDCl3): d=7.77–
7.91 ppm (m, 4H, CHaromatic); 13C NMR (75.4 MHz, CDCl3): d=124.3,
133.3 (Caromatic), 135.0 (Caromatic), 168.6 ppm (C=O); IR: n˜ =3448 (n(NH)),
1747 cmꢀ1 (n(C=O)); MS (FAB+): m/z: 148 [M+H]+; elemental analysis
ACHTREUNG
calcd (%) for C8H5NO2: C 65.31, H 3.43, N 9.52; found: C 65.53, H 3.22,
N 9.83.
1
Compound 3b: Yield: 51%; H NMR (300 MHz, CDCl3): d=2.53 (s, 3H,
CH3), 7.55 (d, JHH =7.2 Hz, 1H, CHaromatic), 7.68 (s, 1H, CHaromatic), 7.76
(d, JHH =7.2 Hz, 1H, CHaromatic), 8.09 ppm (s, br, 1H, NH); 13C NMR
(75.4 MHz, CDCl3): d=22.7 (CH3), 124.2, 124.7, 130.7, 133.7, 135.5
(Caromatic), 146.3 (Caromatic), 168.9 (C=O), 169.0 ppm (C=O); IR: n˜ =3212
(n(NH)), 1725 cmꢀ1 (n(C=O)); MS (FAB+) m/z: 162 [M
ACHTREUNG
H]+; elemental analysis calcd (%) for C9H7NO2: C 67.07, H 4.38, N 8.69;
found: C 67.34, H 4.22, N 9.03.
1
We have thus developed synthetic strategies that involve
cycloaddition reactions of a cyclic nitrone with conveniently
Compound 4c: Yield: 65%; H NMR (300 MHz, CDCl3): d=1.23 (s, 3H,
CH3), 1.35 (s, 3H, CH3), 1.67–1.72 (m, 2H, CH2), 2.09–2.15 (m, 1H,
Chem. Eur. J. 2008, 14, 9312 – 9322
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9319

A. J. L. Pombeiro et al.
CH2), 2.30–2.35 (m, 1H, CH2), 5.75 (dd, JHH =7.2, 2.4 Hz, 1H, NCHN),
7.87 (s, 1H, CHaromatic), 8.09 ppm (s, 1H, CHaromatic); 13C NMR (75.4 MHz,
CDCl3): d=23.9 (CH3), 27.7 (CH3), 31.9 (CH2), 34.6 (CH2), 69.9
2.45 (s, 3H, CH3Ph), 3.47 (t, JHH =7.3 Hz, 4H, two CH2), 7.42–7.58 (m,
3H, CHaromatic), 10.67 ppm (s, br, 2H, NH); 13C NMR (75.4 MHz, CDCl3):
d=21.3 (CH3Ph), 25.2 (CH3), 28.3 (CH3), 30.8 (CH2), 33.9 (CH2), 73.6
(C(Me)2), 129.4, 129.5, 132.1, 133.1, 135.9 (Caromatic), 142.0 (Caromatic),
174.1 ppm (NC=O); IR: n˜ =3433 (n(NH)), 3276 (n(NH)), 1643, 1631 (n-
ꢁ
ꢁ
(C(Me)2), 92.2 (NCHN), 111.8 (N C), 116.1 (N C), 127.9, 132.5, 136.4,
136.5, 137.0 (Caromatic), 138.6 (Caromatic), 157.0 ppm (C=N); IR: n˜ =2234 (n-
(N C)), 1735 (n
(NCO), conjugated), 1648 cmꢀ1 (C=N); MS (FAB+): m/
(NC=O), conjugated), 1589 cmꢀ1 (n
ACHTRE(UNG NC=N) and nACHTREUNG AHCTUEG(RN NC=N) and (nACHTREUNG(NC=
ꢁ
z: 310 [M]+; elemental analysis calcd (%) for C14H13N3OCl2: C 54.21, H
O), conjugated); MS (ESI): m/z: 547 [M+H]+; elemental analysis calcd
for C21H28Cl2N4O2Pd: C 46.21, H 5.17, N 10.27; found: C 46.52, H 5.13, N
10.16.
4.22, N 13.55; found: C 54.56, H 4.15, N 13.12.
1
Compound 4d: Yield: 35%; H NMR (300 MHz, CDCl3): d=1.16 (s, 3H,
1
CH3), 1.39 (s, 3H, CH3), 1.69–1.75 (m, 1H, CH2), 1.89–1.99 (m, 1H,
CH2), 2.13–2.20 (m, 1H, CH2), 2.25–2.35 (m, 1H, CH2), 5.85 ppm (m,
1H, NCHN); 13C NMR (75.4 MHz, CDCl3): d=23.7 (CH3), 26.7 (CH3),
Compound 5c: Yield: 80%; H NMR (400 MHz, CDCl3): d=1.44 (s, 6H,
two CH3), 1.50 (s, 6H, two CH3), 2.07–2.14 (m, 4H, two CH2), 2.56–2.61
(m, 2H, CH2), 3.41–3.52 (m, 2H, CH2), 7.76 (s, 2H, CHaromatic), 10.61 ppm
(s, br, 2H, NH); 13C NMR (100.6 MHz, CDCl3): d=25.3 (CH3), 28.3
(CH3), 30.9 (CH2), 34.0 (CH2), 131.2, 134.9 (Caromatic), 136.1 (Caromatic),
ꢁ
31.9 (CH2), 33.7 (CH2), 70.3 (C(Me)2), 92.5 (NCHN), 112.6 (N C), 114.0
ꢁ
(N C), 130.7, 133.3, 135.9, 136.7 (Caromatic), 139.2 (Caromatic), 154.9 ppm (C=
N); IR: n˜ =2239 (n
G
(NCO), conjugated), 1680 cmꢀ1 (C=
174.5 (NC=O); IR: n˜ =3250 (n(NH)), 1789 (n
A
ACHTREUNG(NC=N),
ꢁ
N); MS (FAB+): m/z: 379 [M]+; elemental analysis calcd (%) for
conjugated), 1600 cmꢀ1 (n
ACHTREUNG
C14H11N3OCl4: C 44.36, H 2.92, N 11.09; found: C 43.87, H 2.43, N, 10.74.
[M+H]+, 623 [M+Na]+, 565 [MꢀCl]+; elemental analysis calcd for
C20H24N4O2Cl4Pd: C 39.99, H 4.03, N 9.33; found: C 40.14, H 4.00, N
9.39; the poor solubility of the complex did not allow the acquisition of
all the 13C signals.
1
Compound 4e: Yield: 70%; H NMR (300 MHz, CDCl3): d=1.18 (s, 3H,
CH3), 1.34 (s, 3H, CH3), 1.69–1.75 (m, 2H, CH2), 2.07–2.16 (m, 1H,
CH2), 2.26–2.34 (m, 1H, CH2), 5.76 ppm (dd, JHH =7.5, 2.7 Hz, 1H,
NCHN); 13C NMR (75.4 MHz, CDCl3): d=23.3 (CH3), 26.8 (CH3), 31.3
Compound 5d: Yield: 85%; 1H NMR (400 MHz, CDCl3 +CD3OD): d=
1.14 (s, 6H, two CH3), 1.20 (s, 6H, two CH3), 1.85 (t, JHH =6.3, 4H, two
CH2), 2.70 ppm (t, JHH =6.3 Hz, 4H, two CH2); 13C NMR (100.6 MHz,
CDCl3 +CD3OD): d=23.5 (CH3), 27.5 (CH3), 30.9 (CH2), 34.8 ppm
ꢁ
ꢁ
(CH2), 33.6 (CH2), 69.6 (C(Me)2), 91.7 (NCHN), 109.3 (N C), 114.3 (N
C), 140.4, 142.4, 145.0, 148.4, 151.7 (Caromatic), 152.5 (Caromatic), 162.3 ppm
ꢁ
(C=N); IR: n˜ =2242 (n
A
G
(C=
N)), 1628 cmꢀ1 (n
A
(CH2); IR: n˜ =3322 (n(NH)), 1793 (n
ACHRTUNEG(NC=O), conjugated), 1737 (nACHTREUNG(NC=
analysis calcd (%) for C14H11N3OF4: C 53.68, H 3.54, N 13.41; found: C
53.72, H, 3.70, N 13.45.
O), conjugated), 1686 cmꢀ1 (n
N
elemental analysis calcd for C20H22N4O2Cl6Pd: C 35.88, H 3.31, N 8.37;
found: C 35.44, H 3.42, N 8.48. The poor solubility of the complex did
not allow the acquisition of all the NMR data.
Synthesis of compound 4e’: A solution of 1e (50.0 mg, 0.249 mmol) in
CHCl3 (2 mL) was added at room temperature to the nitrone 2 (56.4 mg,
0.498 mmol) and the mixture was heated at 808C in a sealed tube for
16 h. After evaporation of the solvent to dryness in vacuo, the crude resi-
due was purified as indicated above to give the corresponding product
4e’.
Compound 4e’: Yield: 30%; 1H NMR (300 MHz, CDCl3): d=1.11 (s,
6H, two CH3), 1.47 (s, 6H, two CH3), 1.79–1.82 (m, 4H, two CH2), 2.21–
2.28 (m, 2H, CH2), 2.44–2.53 (m, 2H, CH2), 6.05 ppm (dd, JHH =12.9,
7.5 Hz, 2H, two NCHN); 13C NMR (75.4 MHz, CDCl3): d=22.2 (CH3),
28.4 (CH3), 29.1 (CH2), 36.6 (CH2), 67.6 (C(Me)2), 103.4 (NCHN), 145.3,
1
Compound 5e: Yield: 90%; H NMR (300 MHz, CDCl3): d=1.37 (s, 6H,
two CH3), 1.41 (s, 6H, two CH3), 2.03 (m, 4H, two CH2), 2.55 (m, 2H,
CH2), 3.74 (m, 2H, CH2), 10.73 ppm (s, br, 2H, NH); 13C NMR
(75.4 MHz, CDCl3): d=25.1 (CH3), 27.8 (CH3), 33.7 (CH2), 35.1 (CH2),
73.5 (C(Me)2), 140.1, 142.8 (Caromatic), 146.2 (Caromatic), 168.6 (C=N), 174.1
(NC=O); IR: n˜ =3339 (n(NH)), 1788 (n
(NC=O), conjugated), 1650 (n
ACHTREUNG
N
A
ACHTREUNG
N), conjugated); MS (FAB+): m/z: 605 [M+H]+; elemental analysis
calcd for C20H22N4O2F4Cl2Pd: C 39.79, H 3.67, N 9.28; found: C 40.01, H
3.76, N 9.40.
151.5 (Caromatic), 153.1 (Caromatic), 162.0 ppm (C=N); IR: n˜ =1786 (nCAHTREUNG
conjugated), 1728 (n
G
G
Synthesis of intermediates 6 and of the dimers 7: Palladium chloride (1
eq) was added to a solution of 4c (50.0 mg, 0.161 mmol) or 4e (50.0 mg,
0.159 mmol) in acetone (8 mL) at room temperature and the mixture was
stirred a) at room temperature until full dissolution of PdCl2 was ob-
served (ca. 12 h) to give intermediates 6 or b) under reflux for 48 h or at
room temperature for 72 h to give dimers 7. During the course of the re-
action, the brown PdCl2 powder dissolved, forming a homogeneous light
yellow solution. In case a), the reaction mixture is then evaporated to
dryness in vacuo, washed with three 10 mL portions of diethyl ether and
dried under air (for 6c) or directly analyzed by ESI MS (for 6e). In case
b), after formation of the yellow solution, a yellow precipitate separates
out. It was then filtered off, washed with acetone (3”10 mL) and dried
under air (7).
(FAB+): m/z: 427 [M+H]+; elemental analysis calcd for C20H22N4O2F4: C
56.33, H 5.20, N 13.14; found: C 56.08, H 5.44, N 13.03.
Reactions of phthalonitriles 1 (1a, R1 =R2 =R3 =R4 =H; 1b, R1 =R2 =
R4 =H, R3 =CH3; 1c, R1 =R4 =H, R2 =R3 =Cl; 1d, R1 =R2 =R3 =R4 =
Cl; 1e, R1 =R2 =R3 =R4 =F) with the cyclic nitrone ꢀO+ N=
CHCH2CH2CMe2 2 in the presence of palladium(II) chloride (PdCl2): A
solution of 1a (50.0 mg, 0.390 mmol), 1b (50.0 mg, 0.352 mmol), 1c
(50.0 mg, 0.254 mmol), 1d (50.0 mg, 0.188 mmol), or 1e (50.0 mg,
0.249 mmol) in acetone (8 mL) was added at room temperature to the ni-
trone 2 (2 equiv) and palladium chloride (1 equiv), and the mixture was
stirred at room temperature for 12 h. During the course of the reaction,
the brown PdCl2 powder dissolved, forming a homogeneous light yellow
solution. The reaction mixture was then dried in vacuo, washed with
three 10 mL portions of diethyl ether and dried under air. The final com-
plex 5 was recrystallized from acetone.
Compound 6c: Yield: 34%; 1H NMR (300 MHz, CDCl3 +CD3OD): d=
1.15 (s, 6H, two CH3), 1.42 (s, 6H, two CH3), 1.70–1.79 (m, 4H, two
CH2), 1.86–1.97 (m, 2H, CH2), 2.37–2.45 (m, 2H, CH2), 5.55 (dd, JHH
=
1
6.2 and 2.7 Hz, 2H, NCHN), 7.89 (s, 2H, CHaromatic), 9.25 ppm (s, 2H,
Compound 5a: Yield: 75%; H NMR (300 MHz, CDCl3): d=1.48 (s, 6H;
CHaromatic); 13C NMR (75.4 MHz, CDCl3 +CD3OD): d=22.7 (CH3), 26.2
two CH3), 1.59 (s, 6H; two CH3), 2.11 (t, JHH =7.2 Hz, 4H; two CH2),
3.45 (t, JHH =7.2 Hz, 4H; two CH2), 7.68 (s, br, 4H; CHaromatic), 10.73 ppm
(s, br, 2H; NH); 13C NMR (75.4 MHz, CDCl3 +CD3OD): d=27.6 (CH3),
30.5 (CH3), 33.7 (CH2), 36.4 (CH2), 64.8 (C(Me)2), 128.8, 131.2 (Caromatic),
135.6 (Caromatic), 169.5 (NC=N), 173.4 ppm (NC=O); IR: n˜ =3285
ꢁ
(CH3), 31.1 (CH2), 33.5 (CH2), 71.4 (C(Me)2), 89.7 (NCHN), 111.9 (N
ꢁ
C), 114.7 (N C), 126.4, 133.6, 133.7, 135.6, 138.0 (Caromatic), 138.2
(Caromatic), 161.6 ppm (C=N); IR: n˜ =2240 (n
(C=N)), 1670, 1642 cmꢀ1 (n-
AHCTREUNG
(OC=N), conjugated); MS (ESI in acetone): m/z: 799 [M+H]+; elemen-
tal analysis calcd for C28H26Cl6N6O2Pd: C 42.16, H 3.29, N 10.54; found:
C 42.21, H 3.26, N 10.57.
(n(NH)), 3237 (n(NH)), 1712 (n
ACHRTUNEG(NC=O)), 1657 (nAHCTRE(UGN NC=N), conjugated),
1591 cmꢀ1 (n(NC=N), conjugated); MS (FAB+): m/z: 554 [M+Na]+, 531
ACHTREUNG
[M]+, 495 [MꢀCl]+, 459 [Mꢀ2Cl]+; elemental analysis calcd for
C20H26N4O2Cl2Pd: C 45.17, H 4.93, N 10.54; found: C 44.77, H 4.83, N
10.61.
Compound 6e: MS (ESI): (of the reaction mixture after 12 h of stirring
at room temperature), m/z: 805 [M+1]+, 732 [Mꢀ2Cl-1]+.
1
Compound 7c: Yield: 70%; H NMR (400 MHz, [D6]DMSO): d=1.64 (s,
1
Compound 5b: Yield: 73%; H NMR (300 MHz, CDCl3): d=1.42 (s, 6H,
12H, four CH3), 1.93 (t, JHH =6.0 Hz, 4H, two CH2), 3.22 (t, JHH =6.0 Hz,
two CH3), 1.44 (s, 6H, two CH3), 2.11 (t, JHH =7.3 Hz, 4H, two CH2),
4H, two CH2), 8.34 (s, 2H, CHaromatic), 9.04 ppm (s, 2H, CHaromatic); 13C
9320
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 9312 – 9322

ACHTREUNG[2+3] Cycloadditions of a Cyclic Nitrone to Phthalonitriles
FULL PAPER
NMR (100.6 MHz, [D6]DMSO), d=27.5 (CH3), 33.4 (CH2), 75.0
(C(Me)2), 127.0, 127.3, 129.6, 129.9, 138.3 and 139.2 (Caromatic), 161.0 (NC=
N), 163.8 ppm (NC=N, NC=O, conjugated); IR: n˜ =1776 (nACHTREUNG
mobenzene (0.785 g, 5.00 mmol), phenylboronic acid (0.73 g, 6.0 mmol),
potassium carbonate (1.38 g, 10.0 mmol), 1 mL of a freshly prepared (see
below) acetone solution of catalyst 5a or 7c containing 5”10ꢀ4–5”
10ꢀ6 mmol of the complex (10ꢀ2–10ꢀ4 mol% Pd relative to bromoben-
zene), and toluene (50 mL). The solution was stirred at 1008C in air, and
the reaction progress was monitored by TLC (hexane/CH2Cl2 10:1).
After completion, the reaction mixture was poured into water (excess)
and extracted with dichloromethane (3”25 mL). The organic extract was
dried with MgSO4 and evaporated in vacuo and the crude residue was
purified by column chromatography on silica (hexane/CH2Cl2 10:1).
Evaporation of the solvent in vacuo afforded the biphenyl product in 90–
jugated), 1687 (nACHTREUNG
[M+H]+; elemental analysis calcd for C28H24Cl6N6O2Pd2: C 37.28, H 2.68,
N 9.32; found: C 37.56, H 2.58, N 9.12. Crystals of 7c were prepared by
slow evaporation of its methanol/chloroform solution.
1
Compound 7e: Yield: 75%; H NMR (400 MHz, [D6]DMSO): d=1.56 (s,
12H, four CH3), 1.95 (t, JHH =8.0 Hz, 4H; two CH2), 3.11 ppm (t, JHH
=
8.0 Hz, 4H; two CH2); 13C NMR (100.6 MHz, [D6]DMSO), d: 27.5
ꢀ
(CH3), 32.4 (CH2), 38.9 (CH2), 76.5 (C(Me)2), 148.4 (C Faromatic), 159.8
1
95% yield (pure by H and 13C NMR).
(NC=N), 162.1 ppm (NC=O, conjugated); IR: n˜ =1787 (n
A
gated), 1707 cmꢀ1 (n
ACHTREUNG(NC=N), conjugated); MS (ESI, DMSO): m/z: 909
The preparation of the catalyst solution was as follows: Catalyst 5a or 7c
(5”10ꢀ3 mmol, 2.65 mg or 4.50 mg of 5a or 7c, respectively) was dis-
solved in acetone (10 mL). By subsequent dilutions, solutions containing
5”10ꢀ4 and 5”10ꢀ5 mmol in acetone (10 mL) (that is, with concentrations
of 5”10ꢀ5 and 5”10ꢀ6 m, respectively) were prepared.
[M+H]+; elemental analysis calcd for C28H20Cl2F8N6O2Pd2: C 37.03, H
2.22, N 9.25; found: C 37.56, H 2.18, N 9.38. The poor solubility of the
complex did not allow collection of all the 13C signals.
Attempts to react 4 with nucleophiles other than the cyclic nitrone 2 in
the presence of palladium(II) chloride: Compound 4c (20.0 mg,
0.064 mmol) or 4e (20.1 mg, 0.064 mmol) was dissolved in acetone,
whereupon PdCl2 (11.4 mg, 0.064 mmol) and the nucleophile
X-ray crystal structure determinations: The X-ray quality single crystals
of 4c, 5a, 5c, and 7c were grown by slow evaporation at room tempera-
ture of their CHCl3 (for 4c and 5a) or CHCl3/MeOH (for 5c and 7c) sol-
utions. They were mounted in inert oil within the cold N2 stream of the
diffractometer. Intensity data were collected by using a Bruker AXS-
KAPPA APEX II diffractometer using graphite monochromated MoKa
radiation. Data were collected at 150 K using omega scans of 0.58 per
frame and a full sphere of data was obtained. Cell parameters were re-
trieved using Bruker SMART software and refined using Bruker SAINT
on all the observed reflections. Absorption corrections were applied
using SADABS. Structures were solved by direct methods by using the
SHELXS-97 package[25] and refined with SHELXL-97[26] with the
WinGX graphical user interface.[27] All hydrogens were inserted in calcu-
lated positions.
(0.064 mmol) (Me2C=NOH, ꢀO+N(Me)=C(H)
ACHTRE(UGN C6H4Me-4) or Et2NOH)
were added. Continuous stirring at room temperature for 72 h led to a
yellow precipitate, which, by IR and NMR spectroscopic analyses, was
shown to be the corresponding dimer 7. Evaporation of the separated so-
lution gave a yellow oil, the main component of which was also the
dimer 7, contaminated with as yet unidentified species.
Liberation of the ketoimine 5e’ from the complex 5e: Dppe (72.6 mg,
0.182 mmol) was added to a solution of 5e (55.0 mg, 0.091 mmol) in
CDCl3 (2 mL) and the mixture was allowed to stand at 408C for 30 min,
whereupon colorless [PdCl2ACHTRE(UNG dppe)] precipitated. This precipitate was sep-
arated by filtration and identified by 31P NMR (161.9 MHz, CDCl3): d=
55.9 (56.7) ppm[22]). The free ketoimine 5e’ was characterized in solution
by NMR spectroscopy.
There are disordered solvents present in structures 5c and 7c. Attempts
were made to model these but were unsuccessful since there were no ob-
vious site occupations for the solvent molecules. PLATON/SQUEEZE[28]
was used to correct the data. Potential solvent volumes of 558 (5c) or
Compound 5e’: Yield: 50%; 1H NMR (400 MHz, CDCl3): d=1.29 (s,
6H, two CH3), 1.42 (s, 6H, two CH3), 1.89 (t, JHH =7.2 Hz, 4H, two
CH2), 2.84 (t, JHH =7.2 Hz, 4H, two CH2), 7.55 ppm (s, br, 2H, NH); 13C
NMR (100.6, CDCl3): d=25.3 (CH3), 28.0 (CH3), 34.0 (CH2), 35.3 (CH2),
73.4 (C(Me)2), 139.8, 141.5 (Caromatic), 145.1 (Caromatic), 169.1 (C=N),
3
324 (7c) Š were found and 64 (5c) or 158 (7c) electrons per unit cell
worth of scattering were located in the voids. The electron counts sug-
gested the presence of ca. one additional water molecule per unit cell in
5c, and one molecule of acetone and one molecule of water in 7c.
172.4 ppm (NC=O); IR: n˜ =3438 (n(NH)), 1739 (nACHTRE(UNG NC=O), conjugated),
1699 (nACHTREUNG ACHTREU(GN NC=N), conjugated); MS
(NC=O), conjugated), 1629 cmꢀ1 (n
The crystallographic details for 4c, 5a, 5c and 7c are summarized in
Table 2. CCDC-681281, CCDC-681282, CCDC-681283, and CCDC-
681284 contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge Crystal-
lographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
(ESI): m/z: 427 [M+H]+; elemental analysis calcd for C20H22F4N4O2: C
56.33, H 5.20, N 13.14; found: C 56.67, H 4.99, N 13.50.
Catalytic Suzuki–Miyaura cross coupling reactions of bromobenzene and
phenylboronic acid: A 100 mL round-bottom flaskwas charged with bro-
Table 2. Crystal data and structure refinement details for compounds 4c, 5a, 5c, and 7c.
4c
5a·CHCl3
5c·C3H6O·H2O
7c·2CHCl3
empirical formula
Mr
T [K]
l [Š]
crystal system
space group
a [Š]
b [Š]
c [Š]
C14H13N3OCl2
310.17
150(2)
0.71069
monoclinic
P21/c
16.753(2)
6.3621(6)
14.428(3)
113.704(4)
1408.1(4)
4
C20H26N4O2Cl2Pd
651.14
150(2)
C20H24N4O2Cl4Pd
676.75
150(2)
C28H24Cl6N6O2Pd2·2CHCl3
1140.81
150(2)
0.71069
monoclinic
C2/c
11.6758(14)
17.012(2)
21.064(3)
100.580(5)
4112.7(9)
4
0.71069
monoclinic
P21/c
13.3550(11)
14.8346(11)
15.0941(10)
122.999(3)
2508.0 (3)
4
0.71069
monoclinic
I2/a
21.5056(13)
12.6768(8)
22.3470(18)
102.571(3)
5946.2(7)
4
b [8]
V [Š3]
Z
1calcd [Mgmꢀ3
]
1.463
0.459
1.724
1.300
1.512
1.018
1.842
1.692
m
A
]
no. of collected reflections
no. of unique reflections
R1[a] (Iꢃ2s)
7379
2385
0.0426
0.0947
2
13623
4387
0.0621
0.1438
37425
5417
0.0318
0.0700
7824
3649
0.0465
0.1171
wR2[b] (Iꢃ2s)
2
[a] R1 =ꢀjjFo jꢀjFc jj/ꢀjFo j. [b] wR2 =[ꢀ[w
A
(Fo )2]]1/2
ACHTREUNG .
Chem. Eur. J. 2008, 14, 9312 – 9322
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9321

A. J. L. Pombeiro et al.
Zalesov, N. A. Podushkina, Pharm. Chem. J. 1980, 14, 99; c) J.-J. Lu,
H. L. Wehrmeister, US-A 4694016, 1987; d) A. Guidi, F. Pasqui, M.
Almatura, C. A. Maggi, WO/2002/020437, 2002; e) K. Sakata, M.
Morimoto, H. Kodama, T. Nishimatsu, WO/2002/087334, 2002.
[14] a) D. Dallinger, C. O. Kappe, Chem. Rev. 2007, 107, 2563;
b) E. A. B. Kantchev, C. J. OꢁBrien, M. G. Organ, Angew. Chem.
2007, 119, 2824; Angew. Chem. Int. Ed. 2007, 46, 2768; c) J. Hassan,
M. Se’vignon, C. Gozzi, E. Schulz, M. Lemaire, Chem. Rev. 2002,
102, 1359; d) S. Kotha, K. Lahiri, D. Kashinath, Tetrahedron 2002,
58, 9633; e) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457.
[15] K. B. G. Torssell, Nitrile Oxides, Nitrones, and Nitronates in Organic
Synthesis, Wiley, 1988.
Acknowledgements
This workhas been partially supported by the Fundażo para a CiÞncia e
a Tecnologia (FCT) and its POCI 2010 program (FEDER funded) (Por-
tugal). J. L. and M. N. K. express gratitude to FCT for their post-doc fel-
lowships (grants SFRH/BPD/20927/2004 and SFRH/BPD/14465/2003),
and to the FCT and the Instituto Superior TØcnico (IST) for a research
contracts (CiÞncia 2007 program). Thanks are also due to Dr. M. C. Vaz
(microanalytic service), Dr. C. Oliveira and Dr. K. Koci (ESI MS) and
Mr. I. Marques (FAB MS) for the analytical services.
[16] K. V. Luzyanin, V. Yu. Kukushkin, M. N. Kopylovich, A. A. Naza-
rov, M. Galanski, A. J. L. Pombeiro, Adv. Synth. Catal. 2008, 350,
135.
[17] a) E. S. H. El Ashry, Y. El Kilany, N. Rashed, H. Assafir, Adv. Heter-
ocycl. Chem. 2000, 75, 79; b) J. Liebscher, A. Hassoun, H. van der
Plas, C. Stam, J. Heterocycl. Chem. 1990, 27, 1441.
[1] a) G. Desimoni, G. Faita, K. A. Jorgensen, Chem. Rev. 2006, 106,
3561; b) H. A. McManus, P. J. Guiry, Chem. Rev. 2004, 104, 4151;
c) A. J. Phillips, A. D. Abell, Aldrichimica Acta 1999, 32, 75.
[2] a) D. Lednicer, New Drug Discovery and Development, Wiley, 2007;
b) Drug Discovery and Development, (Ed.: M. S. Chorghade), Wiley,
2006.
[18] a) L. Eberson, J. J. McCullough, C. M. Hartshorn, M. P. Hartshorn,
J. Chem. Soc. Perkin Trans. 2 1998, 1, 41; b) L. Eberson, C. M.
Hartshorn, M. P. Hartshorn, J. J. McCullough, Synth. Commun.
1997, 27, 3779; c) L. A. G. M. Van den Broek, Tetrahedron 1996, 52,
4467; d) H. Sang, E. G. Janzen, L. Poyer, J. Chem. Soc. Perkin Trans.
2 1996, 6, 1183; e) Y. Yu, N. Watanabe, M. Ohno, S. Eguchi, J.
Chem. Soc. Perkin Trans. 1 1995, 11, 1417; f) Y. Yu, H. Fujita, M.
Ohno, S. Eguchi, Synthesis 1995, 498; g) Y. Yu, M. Ohno, S. Eguchi,
J. Chem. Soc. Chem. Commun. 1994, 331; h) P. H. H. Hermkens,
J. H. van Maarseveen, C. G. Kruse, H. W. Scheeren, Tetrahedron
1988, 44, 6491; i) R. Plate, P. H. H. Hermkens, J. M. M. Smits, R. J. F.
Nivard, H. C. J. Ottenheijm, J. Org. Chem. 1987, 52, 1047.
[19] F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G. Orpen, J.
Chem. Soc. Perkin Trans. 2, 1987, S1-S19.
[20] a) M. N. Kopylovich, M. Haukka, A. M. Kirillov, V. Yu. Kukushkin,
A. J. L. Pombeiro, Chem. Eur. J. 2007, 13, 786; b) M. N. Kopylovich,
V. Yu. Kukushkin, M. Haukka, K. V. Luzyanin, A. J. L. Pombeiro, J.
Am. Chem. Soc. 2004, 126, 15040.
[21] a) B. Desai, T. N. Danks, G. Wagner, Dalton Trans. 2003, 2544;
b) G. A. Anderson, M. Lin, Inorg. Synth. 1990, 28, 60; c) M. A. An-
drews, T. C. T. Chang, C. W. F. Cheng, T. J. Emge, K. P. Kelly, T. F.
Koetzle, J. Am. Chem. Soc. 1984, 106, 5913.
[22] a) N. A. Bokach, V. Yu. Kukushkin, M. Haukka, A. J. L. Pombeiro,
Eur. J. Inorg. Chem. 2005, 845; b) P. S. Jarrett, O. M. Ni Dhubh-
ghaill, P. J. Sadler, J. Chem. Soc. Dalton Trans. 1993, 1863.
[23] a) L. Ray, M. N. Shaikh, P. Ghosh, Organometallics 2007, 26, 958;
b) L. Braun, P. Liptau, G. Kehr, J. Ugolotti, R. Frohlich, G. Erker,
Dalton Trans. 2007, 1409; c) H. Hagiwara, K. H. Ko, T. Hoshi, T.
Suzuki, Chem. Commun. 2007, 2838; d) Q. Luo, S. Eibauer, O.
Reiser, J. Mol. Cat. A 2007, 268, 65; e) J. K. Eberhardt, R. Frçhlich,
E.-U. Wꢂrthwein, J. Org. Chem. 2003, 68, 6690.
[24] D. Dçpp, H. Dçpp, in: Houben-Weyl Methoden der Organischen
Chemie Vol. E14b, part 2, (Eds.: D. Klamann, H. Hagemann),
Thieme, Stuttgart, Germany, 1990, 1372.
[25] G. M. Sheldrick, Acta Crystallogr. Sect. A 1990, 46, 467.
[26] G. M. Sheldrick, SHELXL-97, University of Gottingen, Germany,
1997.
[3] a) The Chemistry of b-Lactams, (Ed.: M. I. Page), Chapman and
Hall, London, 1997; b) A. Chimirri, S. Grasso, A.-M. Montforte, A.
Rao, M. Zappala, Farmaco 1996, 51, 125.
[4] a) N. B. McKeown, “Phthalocyanines”, in: Comprehensive Coordina-
tion Chemistry II Vol. 1, 2nd ed. (Ed.: A. B. P. Lever), Elsevier, Am-
sterdam, 2003, Chapter 1.24.and references therein; b) Phthalocya-
nines. Properties and Applications Vols. 1–4, (Eds.: C. C. Leznoff,
A. B. P. Lever) Wiley, Weinheim 1982, 1989, 1993, 1996.
[5] P. Gregory, “Metal Complexes as Speciality Dyes and Pigments”, in
Comprehensive Coordination Chemistry II Vol. 9, 2nd ed., (Ed.
A. B. P., Lever), Elsevier, Amsterdam, 2003, Chapter 9.12. and refer-
ences therein.
[6] a) A. S. Polo, M. K. Itokazu, K. M. Frin, A. O. de Toledo Patrocínio,
N. Y. Murakami Iha, Coord. Chem. Rev. 2006, 250, 1669; b) B. Hig-
gins, B. A. DeGraff, J. N. Demas, Inorg. Chem. 2005, 44, 6662; c) J.-
M. Lehn, Supramolecular Chemistry: Concepts and Perspectives,
Wiley, Weinheim, 1995.
[7] a) L. X. Yin, J. Liebscher, Chem. Rev. 2007, 107, 133; b) Metal-cata-
lyzed Cross-coupling Reactions, (Eds.: F. Diederich, P. J. Stang),
Wiley, Weinheim, 2001; c) J. Tsuji, Palladium Reagents and Cata-
lysts-Innovations in Organic Synthesis, Wiley, Chichester, 1997.
[8] a) S. Kobayashi, K. A. Jorgensen, Cycloaddition Reactions in Organ-
ic Synthesis, Wiley, Weinheim, 2002; b) K. V. Gothelf, K. A. Jorgen-
sen, Chem. Rev. 1998, 98, 863; c) K. V. Gothelf, K. A. Jorgensen,
Chem. Commun. 2000, 1449.
[9] a) V. Yu. Kukushkin, A. J. L. Pombeiro, Chem. Rev. 2002, 102, 1771;
b) R. A. Michelin, M. Mozzon, R. Bertani, Coord. Chem. Rev. 1996,
147, 299.
[10] N. A. Bokach, A. A. Krokhin, A. A. Nazarov, V. Yu. Kukushkin, M.
Haukka, J. J. R. Frafflsto da Silva, A. J. L. Pombeiro, Eur. J. Inorg.
Chem. 2005, 3042.
[11] a) J. Lasri, M. A. Charmier Januµrio, M. F. C. Guedes da Silva,
A. J. L. Pombeiro, Dalton Trans. 2007, 3259; b) J. Lasri, M. A.
Charmier Januµrio, M. Haukka, A. J. L. Pombeiro, J. Org. Chem.
2007, 72, 750; c) M. A. Charmier Januµrio, V. Yu. Kukushkin,
A. J. L. Pombeiro, Dalton Trans. 2003, 2540; d) G. Wagner, M.
Haukka, J. J. R. Frafflsto da Silva, A. J. L. Pombeiro, V. Yu. Kukush-
kin, Inorg. Chem. 2001, 40, 264; e) G. Wagner, A. J. L. Pombeiro, V.
Yu. Kukushkin, J. Am. Chem. Soc. 2000, 122, 3106.
[27] L. J. Farrugia, J. Appl. Crystallogr. 1999, 32, 837.
[28] A. L. Spek, Acta Crystallogr. Sect. A 1990, 46, C34.
[12] M. A. Charmier Januµrio, M. Haukka, A. J. L. Pombeiro, Dalton
Trans. 2004, 2741.
[13] a) I. Ando, T. Ohtsuka, N. Miki, T. Takahashi, Y. Hayase, Y. Haya-
shi, Agric. Biol. Chem. 1989, 53, 2001; b) Yu. S. Andreichikov, V. V.
Received: March 19, 2008
Published online: August 26, 2008
9322
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 9312 – 9322