N,N-Dialkyl-2-iodoanilines: A versatile source for the synthesis of Pd(ii) complexes. Synthesis of novel OCP- and CCN-pincer palladium complexes

Article abstract of DOI:10.1039/b708306h

The reactivity of a series of N,N-dimethyl-2-iodoanilines bearing different chelating "arms" at the 3-position with Pd₂(dba) ₃ has been explored. 3-[(Diphenylphosphino)methyl]-2-iodo-N,N- dimethylaniline (1) reacted with Pd₂

Full text of DOI:10.1039/b708306h

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N,N-Dialkyl-2-iodoanilines: A versatile source for the synthesis of Pd(II)
complexes. Synthesis of novel OCP- and CCN-pincer palladium complexes†
Daniel Sole´,*a Xavier Solansb and Merce´ Font-Bardiab
Received 1st June 2007, Accepted 27th July 2007
First published as an Advance Article on the web 15th August 2007
DOI: 10.1039/b708306h
The reactivity of a series of N,N-dimethyl-2-iodoanilines bearing different chelating “arms” at the
3-position with Pd2(dba)3 has been explored. 3-[(Diphenylphosphino)methyl]-2-iodo-N,N-
dimethylaniline (1) reacted with Pd2(dba)3 and PPh3 under aerobic conditions to give the OCP-pincer
complex 4, which was formed by sequential C(sp3)–H activation/oxidation at the a-position of the
aniline N atom. On the other hand, under similar reaction conditions, 3-[2-(dimethylamino)ethyl]-2-
iodo-N,N-dimethylaniline (2) afforded the CCN-pincer complex 5, after a second C–H activation
process at the formyl group of the initially formed OCN-pincer complex. In contrast, 2-iodo-3-(1H-1,2,
4-triazol-1-ylmethyl)-N,N-dimethylaniline (3a) and 2-iodo-3-(pyrazol-1-ylmethyl)-N,N-dimethylaniline
(3b) reacted with Pd2(dba)3 and PPh3, respectively, to give the 6-membered azapalladacycles 6a and 6b,
in which the aniline nitrogen is merely a spectator substituent. Finally, treatment of iodide complex 6a
with Tl(TfO) afforded the CN-bidentate cationic complex 8. Solid-state structures of palladium
complexes 4, 5, and 8·CH2Cl2·3CH3OH·5H2O were determined by X-ray analysis.
strain around the metal centre, which could be responsible for
the intramolecular alkylamino C–H activation and subsequent
aerobic oxidation leading to B. Hoping to gain more information
about this process, we decided to synthesize some N,N-dimethyl-2-
Introduction
Pincer complexes containing tridentate monoanionic ligands
(LCLꢀ), which are connected to the metal via an anionic aryl
carbon atom and two mutually trans-chelating donor sites at the
2,6-positions of the aromatic ring, have attracted considerable
iodoanilines bearing different chelating “arms” at the 3-position,
and study their reaction with Pd2(dba)3. In this context, in order to
attention since their first appearance in the late 1970s.1 The
evaluate if the different electron-donor properties of the phosphine
majority of investigations have been carried out with symmetrical
and the amine ligands could modify the course of the oxidation
pincer-type complexes bearing two equivalent chelate rings (usu-
process, iodoaniline 1 bearing a P donor instead of the N donor
ally five-membered or less commonly six-membered). In contrast,
has been studied. On the other hand, we considered that it
asymmetrical pincer complexes with mixed donor atoms or ring
sizes have been scarcely studied.2
In the context of our studies about the introduction of four-
membered azapalladacycles into tridentate palladium complexes,3
would also be interesting to attempt the synthesis of less strained
pincer complexes. To this end, we have focused on the reactions
of substrates 2 and 3a,b, which would afford palladium pincer
complexes bearing a six-membered metallacycle instead of the
we have recently reported the synthesis of palladium OCN-pincer
five-membered chelate. We report here that the reactivity of the
complexes (i.e., B) derived from N,N-dialkyl-3-[(dialkylamino)-
N,N-dimethyl-2-iodoanilines bearing chelating “arms” at the 3-
methyl]-2-iodoanilines by means of an unprecedented oxidation
position with Pd2(dba)3 is strongly dependent on the nature of the
process (Scheme 1).4 During this work, we realized that the
“arm”, which obliges the aniline nitrogen atom to act as a spectator
initially formed NCNꢀ-pincer complex A, having simultaneously a
4- and a 5-membered chelate ring, would have severe bond angle
substituent or as a participant in metal-centred reactions such as
the previously reported C–H activation/oxidation sequence.
Scheme 1 Synthesis of OCN-pincer complexes.
aLaboratori de Qu´ımica Orga`nica, Facultat de Farma`cia, Universitat
Results
de Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain. E-mail:
dsole@ub.edu; Fax: +34 93 402 45 39; Tel: +34 93 402 45 40
bDepartament de Cristal·lografia, Mineralogia i Dipo`sits Minerals, Univer-
Synthesis of iodoanilines 1, 2, and 3a,b
sitat de Barcelona, Mart´ı i Franque`s s/n, 08028, Barcelona, Spain
The new iodoanilines were prepared from 3-(dimethylamino)-2-
iodobenzyl chloride (Scheme 2). Phosphine 1 was prepared from
† CCDC reference numbers 649320–649322. For crystallographic data in
CIF or other electronic format see DOI: 10.1039/b708306h
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Scheme 4
Scheme 2 Synthesis of 2-iodoanilines 1, 2, and 3a,b.
the latter following the protocol developed by Zhang et al.,5 which
involves a nucleophilic attack with LiPPh2(BH3) and subsequent
removal of the BH3 group. On the other hand, iodoaniline
2 was synthesized from the benzyl chloride by a sequence of
reactions involving treatment with sodium cyanide, reduction of
the nitrile with the BH3·THF complex, and finally methylation
of the resulting primary amine. Finally, reaction of the benzyl
chloride with 1,2,4-triazole sodium salt and with pyrazole afforded
iodoanilines 3a and 3b, respectively.
conditions and in the presence of PPh3 (1 equiv.), iodoaniline
3a afforded palladium complex 6a7 in 31% yield (Scheme 5).
When the reaction was carried out under an argon atmosphere
a cleaner mixture was obtained and the yield of 6a increased to
67%. A similar reaction was observed starting from iodoaniline
3b, which on treatment with Pd2(dba)3 and PPh3 (0.6 : 1 molar
ratio) under argon afforded palladium complex 6b8 in 75% yield.
Palladium complexes 6a,b are robust compounds that can be
purified by flash chromatography without decomposition and
1
were characterized by elemental analysis and H, 13C, and 31P
NMR spectra. It is noteworthy that pincer complexes could not be
obtained either from anilines 3a,b or palladium complexes 6a,b.
Thus, treatment of 3a with Pd2(dba)3 in the absence of PPh3 under
an argon atmosphere afforded aniline 7 (47%), resulting from the
hydrodehalogenation and demethylation of the starting material.4
On the other hand, when palladium complex 6a was treated with
Tl(TfO) to remove the iodo ligand and facilitate the coordination
of the dimethylamino group, the vacant coordination site was
occupied by the N-4 of a different triazole unit and cationic
azapalladacycle 8 was obtained instead (60%).
Synthesis and characterization of palladium complexes
The studies were begun with iodoaniline 1 bearing a P donor
connected to the aromatic ring by a methylene unit. Treatment
of 1 with Pd2(dba)3 and PPh3 (0.6 : 1 molar ratio) in open
air afforded OCP-pincer complex 4 (47%), resulting from the
sequential C(sp3)–H activation6 and aerobic oxidation at the a-
position of the aniline N atom (Scheme 3).4
Scheme 3
Iodoaniline 2 bearing a dimethylene unit as the connector
of the aromatic ring and the amine chelating site behaved very
differently from the previously studied systems. We expected that
both the flexibility of the aliphatic chain and the increased size of
one of the rings would decrease the strain around the palladium
atom and allow the [4,6]-NCNꢀ-pincer complex C to be isolated.
However, all the attempts to prepare this target were unsuccessful.
Thus, the reaction of 2 with Pd2(dba)3 (benzene, rt) under an
argon atmosphere resulted in the formation of a complex reaction
mixture and the deposition of the Pd metal. On the other hand,
under aerobic reaction conditions [Pd2(dba)3 and PPh3 (0.6 :
1 molar ratio), benzene, rt, open air] iodoaniline 2 afforded binu-
clear palladium(II) complex 5 (85% yield) instead of the expected
palladium OCN-pincer complex D (Scheme 4). The structure of
complex 5 was confirmed by X-ray crystallography (Fig. 2).
Finally, we studied iodoanilines 3a,b, bearing a nitrogen
heterocycle as the pendant ligand. Under aerobic reaction
Scheme 5 Synthesis of palladium complexes 6a,b and 8.
The molecular structures of complexes 4, 5, and 8·CH2Cl2·
3CH3OH·5H2O have been determined by X-ray diffraction studies
and are shown in Fig. 1–3, respectively.
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Fig. 1 Thermal ellipsoid representation (50%) of the molecular structure
˚
of 4. Hydrogen atoms are omitted for clarity. Selected distances (A)
and angles (◦): Pd–I = 2.6858(10), Pd–P = 2.1908(8), Pd–O = 2.039(2),
Pd–C19 = 2.009(3); C19–Pd–O = 91.15(10), C19–Pd–P = 84.96(8),
O–Pd–I = 89.71(6), P–Pd–I = 94.19(3).
Fig. 3 View of tetrameric cation from crystal structure of 8·CH2Cl2·
3CH3OH·5H2O. Hydrogen atoms and the phenyl groups of PPh3 lig-
◦
˚
ands are omitted for clarity. Selected distances (A) and angles ( ):
Pd1–P1 = 2.2678(12), Pd1–N1 = 2.087(3), Pd1–N9 = 2.178(4), Pd1–C9 =
1.995(4), P1–Pd1–N9 = 92.07(11), N1–Pd1–N9 = 92.61(15), N1–Pd1–
C9
=
85.82(17), P1–Pd1–C9
=
90.26(13), Pd2–P2
=
2.2671(13),
Pd2–N5 = 2.101(4), Pd2–N3 = 2.155(4), Pd2–C40 = 2.019(5), P2–Pd2–
N3 = 93.72(11), N3–Pd2–N5 = 92.26(16), N5–Pd2–C40 = 85.61(18),
P2–Pd2–C40 = 89.76(14), Pd3–P3 = 2.2749(14), Pd3–N10 = 2.103(4),
Pd3–N7 = 2.136(3), Pd3–C67 = 1.985(4), P3–Pd3–N7 = 93.08(10), N7–
Pd3–N10 = 91.14(14), N10–Pd3–C67 = 85.64(19), P3–Pd3–C67 =
91.37(16), Pd4–P4 = 2.2836(13), Pd4–N14 = 2.103(4), Pd4–N12 =
2.157(4), Pd4–C96 = 2.011(5), P4–Pd4–N12 = 91.97(12), N12–Pd4–N14 =
93.16(16), N14–Pd4–C96 = 84.76(19), P4–Pd4–C96 = 91.58(15).
The structure of complex 8·CH2Cl2·3CH3OH·5H2O consists
of a tetranuclear cluster of palladium atoms where each 1,2,4-
triazole “arm” acts as a bidentate ligand bridging two palladium
centres. This arrangement of the tetrameric cation results in a
“four-membered ring” with a palladium atom in each vertex,
which adopts a CR form and has a pseudo twofold axis.
The four trifluoromethanesulfonate ions are non-equivalent by
crystallographic symmetry and play different roles in the crystal
structure. Thus, while two trifluoromethanesulfonate ions make
p-ring interactions with two vicinal triazole rings [distance of
S(1)–O(103) to the aromatic centroid of N(5)–N(7) triazole ring =
Fig. 2 Thermal ellipsoid representation (50%) of the molecular structure
˚
of 5. Hydrogen atoms are omitted for clarity. Selected distances (A)
and angles (◦): Pd–O = 2.171(3), Pd–N = 2.184(4), Pd–C7 = 1.865(5),
Pd–C12 = 2.002(4); C7–Pd–C12 = 80.87(19), C12–Pd–O = 96.70(14),
C7–Pd–N = 97.14(17), O–Pd–N = 85.41(13).
In OCN-pincer palladium complex 4 the palladium atom shows
a square-planar coordination, the largest deviation from the
˚
main plane being in the C atom [deviation 0.034(2) A]. The six-
˚
2.971(6) A and distance of S(2)–O(203) to the aromatic centroid
membered [C,O] chelate ring is planar while the five-membered
[C,P] chelate ring has an envelope form with the phosphorus being
the out-of-plane atom.
Binuclear palladium complex 5 has a crystallographic cen-
tre that relates two asymmetric units [j3N,C,C-C6H3{CH2-
CH2NMe2}-2-{N(Me)C(O)}-6] through two acyl bridges. The
oxygen atom of the acyl ligand of one palladium centre is bonded
to the second palladium atom. This arrangement results in a planar
form for the six-membered ring formed by the two palladium
atoms and two CO bridges, which leads to a Pd–Pd distance
˚
of N(1)–N(3) triazole ring = 3.025(5) A] and are hydrogen bonded
to the solvate molecules, the other two trifluoromethanesulfonate
ions are only hydrogen bonded to the solvates. The palladium
atoms show a tetrahedral distorted square-planar coordination,
the largest deviation from the main plane being in the C atom of
˚
˚
the aromatic ring [deviation of 0.151(4) A for Pd(1), 0.193(5) A
˚
˚
for Pd(2), 0.179(5) A for Pd(3), and 0.195(5) A for Pd(4)]. The
six-membered chelate ring has a boat form and the plane of the
aromatic ring is twisted out of the coordination plane [58.4(2)◦
for Pd(1), 59.7(2)◦ for Pd(2), 58.1(2)◦ for Pd(3), and 56.8(2)◦ for
Pd(4)].
˚
of 3.923(3) A, significantly greater than those found in related
compounds.9 The six-membered [C,N] chelate ring has a screw-
boat form and the five-membered [C,C] chelate ring has an
envelope form with the palladium atom being the out-of-plane
atom. The palladium atom shows a square-planar coordination,
the largest deviation from the main plane being in the C atom
Discussion
Among the different iodoanilines explored in this work, only
˚
[deviation 0.084(4) A].
the NCP-based system 1 showed a similar behaviour to those
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previously studied by us4 and afforded the expected OCL-pincer
complex (4). Thus, it becomes clear that the robust coordina-
tion of the phosphine “arm” with the palladium atom in the
initially formed NCP-pincer complex can not overcome the high
strain associated with the simultaneous presence of a 4- and
5-membered chelate ring, which is the origin of the C(sp3)–H
activation/oxidation process leading to 4.
On the other hand, the formation of palladium complex 5 in the
reaction of “long arm” iodoaniline 2 with Pd2(dba)3 is expected to
proceed via intramolecular C–H activation of the formyl group10 in
the initially formed OCN-pincer complex D. It is worth noting that
this activation reaction was not observed either in the OCN-pincer
complexes previously reported by us (i.e., B) or in the OCP-pincer
complex 4, both bearing a methylene unit as a connector of the
aromatic ring and donor group. Although the precise mechanism
of this C–H activation has not been established, the different
behaviour could be understood taking into account that the longer
amine “arm” provides additional reactivity possibilities, since its
labile coordination could assist the facile generation of the vacant
site required for the C–H activation process in palladium complex
D.11 On the other hand, although not incorporated in the final
products, PPh3 has an active role in the oxidation reactions leading
to OCP-pincer complex 4 and CCN-pincer complex 5 (Schemes 3
and 4), as we have demonstrated in our reported synthesis of the
OCN-pincer complex B.4
and dichloromethane. The organic layer was washed with brine,
dried, and concentrated. The residue was purified by chromatog-
raphy (SiO2, from hexanes to 8 : 2 hexanes–EtOAc) to give 3-
1
(dimethylamino)-2-iodobenzyl alcohol (0.76 g, 80%). H NMR
(CDCl3, 200 MHz): d 2.75 (s, 6H), 4.73 (s, 2H), 7.06 (dd, J =
7.8 and 1.8 Hz, 1H), 7.18 (dd, J = 7.8 and 1.8 Hz, 1H), 7.32 (t,
J = 7.8 Hz, 1H). 13C NMR (CDCl3, 50 MHz): d 45.3 (CH3), 70.4
(CH2), 101.8 (C), 119.9 (CH), 123.8 (CH), 128.9 (CH), 144.4 (C),
155.2 (C). Anal. calc. for C9H12INO: C, 39.01; H, 4.36; N, 5.05%.
Found: C, 38.67; H, 4.36; N, 5.00%.
3-(Dimethylamino)-2-iodobenzyl chloride. A solution of 3-
(dimethylamino)-2-iodobenzyl alcohol (0.57 g, 2.06 mmol) and
triethylamine (1.6 mL, 11.3 mmol) in dichloromethane (15 mL)
was cooled to 0 ◦C under argon, and methanesulfonyl chloride
(0.8 mL, 10.3 mmol) was added dropwise. The solution was
stirred at room temperature for 3 d. The mixture was poured
into saturated aqueous NaHCO3 solution and extracted with
dichloromethane. The organic layer was dried and concentrated
to give 3-(dimethylamino)-2-iodobenzyl chloride (0.6 g, quanti-
1
tative), which was used in the next step without purification. H
NMR (CDCl3, 200 MHz): d 2.75 (s, 6H), 4.78 (s, 2H), 7.08 (dd,
J = 7.8 and 1.5 Hz, 1H), 7.20 (dd, J = 7.8 and 1.5 Hz, 1H), 7.30
(t, J = 7.8 Hz, 1H). 13C NMR (CDCl3, 75.4 MHz): d 45.1 (CH3),
52.6 (CH2), 103.9 (C), 120.6 (CH), 125.3 (CH), 128.9 (CH), 141.4
(C), 155.9 (C).
Finally, the different behaviour of anilines 3a,b is probably a
consequence of the chelate stability of six-membered metallacycles
with coordination of heterocyclic nitrogens being higher than
that of the “long arm” aliphatic amine. Moreover, although we
failed to obtain single crystals of 6a and 6b suitable for X-ray
analysis, it is expected that, as in the case of cationic complex 8
and as is usual for this kind of complex,7a,8a the six-membered
metallacycle adopts a boat conformation, in which the plane of
coordination is twisted out of the plane of the benzene ring.
For instance, in cationic complex 8 the planes of coordination
of the Pd atoms are twisted 56.8(2)–59.7(2)◦ out of the planes of
the arene rings. In complexes 6a,b this twisting, which is much
greater than that observed in similar six-membered palladacycles
lacking the dimethylamino substituent,7a,8a avoids the severe steric
interactions with the dimethylamino group and allows the PPh3
ligand to occupy the fourth coordination site.
It should be noted, however, that in the absence of PPh3,
the C(sp3)–H activation process at the N-methyl group of
3a did take place, as evidenced by the isolation of aniline
7 (vide supra). We have previously observed the formation
of such hydrodehalogenation-dealkylation products in the re-
actions of N,N-dialkyl-3-[(dialkylamino)methyl]-2-iodoanilines
with Pd2(dba)3 in the absence of PPh3, in a process in which the
alkyl group is removed as the respective aldehyde.4
[3-(Dimethylamino)-2-iodobenzyl]diphenylphosphino-borane.
A
solution of HPPh2(BH3) (220 mg, 1.1 mmol) in THF (3 mL) was
cooled to −78 ◦C, and a 1.6 M solution of n-BuLi in hexane
(0.63 mL, 1 mmol) was added dropwise. The resulting solution
was brought slowly to room temperature and then added dropwise
to a cooled (−20 ◦C) solution of 3-(dimethylamino)-2-iodobenzyl
chloride (270 mg, 0.9 mmol) in THF (3 mL). The reaction
was maintained at −20 ◦C for 20 h and then warmed to room
temperature. The mixture was poured into water and extracted
with Et2O. The organic layer was dried and concentrated.
The residue was purified by chromatography (SiO2, from
hexanes to 1 : 1 hexanes–EtOAc) to give [3-(dimethylamino)-2-
iodobenzyl]diphenylphosphino-borane (334 mg, 81%). 1H NMR
(CDCl3, 300 MHz): d 2.59 (s, 6H), 4.03 (d, J = 11.7 Hz, 2H), 6.98
(dt, J = 7.5 and 1.5 Hz, 1H), 7.11 (dt, J = 7.5 and 1.5 Hz, 1H),
7.21 (t, J = 7.5 Hz, 1H), 7.38–7.72 (m, 10H). 13C NMR (CDCl3,
75.4 MHz): d 39.5 (d, J = 31.1 Hz, CH2), 45.0 (s, CH3), 107.7 (d,
J = 5.7 Hz, C), 119.1 (d, J = 2.9 Hz, CH), 126.1 (d, J = 4.0 Hz,
CH), 127.7 (d, J = 56.5 Hz, C), 128.3 (d, J = 9.8 Hz, CH), 128.6
(d, J = 4.0 Hz, CH), 131.1 (d, J = 2.3 Hz, CH), 132.8 (d, J =
8.7 Hz, CH), 137.3 (d, J = 4.6 Hz, C), 155.5 (d, J = 2.3 Hz, C).
31P NMR (CDCl3, 121.5 MHz): d 36.5. HRMS (ESI-TOF): m/z
460.0843 (M + H)+.
3-[(Diphenylphosphino)methyl]-2-iodo-N,N -dimethylaniline
(1). To a solution of [3-(dimethylamino)-2-iodobenzyl]diphenyl-
phosphino-borane (325 mg, 0.7 mmol) in dichloromethane (5 mL)
at −5 ◦C was added HBF4·OMe2 (0.17 mL, 1.4 mmol). The reac-
tion was warmed slowly to room temperature and stirred for 18 h.
Dichloromethane (5 mL) was added and the resulting solution was
transferred into a degassed saturated aqueous NaHCO3 solution
via cannula. The resulting mixture was stirred and the organic layer
was removed via cannula. The NaHCO3 phase was extracted twice
Experimental
Procedures for the synthesis of the starting iodoanilines
3-(Dimethylamino)-2-iodobenzyl alcohol. A mixture of 3-
amino-2-iodobenzyl alcohol12 (0.85 g, 3.43 mmol), K2CO3 (0.97 g,
6.99 mmol), and CH3I (1.33 mL, 21 mmol) in CH3CN (15 mL)
was stirred at 50 ◦C in a sealed tube for 24 h. The solvent
was evaporated and the residue was partitioned between water
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with dichloromethane. The combined organic layers were washed
with brine, dried, and concentrated to give [3-(dimethylamino)-2-
iodobenzyl]diphenylphosphine (280 mg, 90%), which was used in
the next step without purification. 1H NMR (CDCl3, 300 MHz):
d 2.69 (s, 6H), 3.68 (s, 2H), 6.51 (dt, J = 7.5 and 1.5 Hz, 1H), 6.85
(dt, J = 7.5 and 1.5 Hz, 1H), 6.97 (t, J = 7.5 Hz, 1H), 7.26–7.32
(m, 6H), 7.38–7.50 (m, 6H). 13C NMR (CDCl3, 75.4 MHz): d 42.6
(d, J = 16.7 Hz, CH2), 45.3 (s, CH3), 106.3 (d, J = 5.2 Hz, C),
118.1 (d, J = 2.9 Hz, CH), 125.5 (d, J = 8.0 Hz, CH), 127.9 (d, J =
1.1 Hz, CH), 128.2 (d, J = 6.9 Hz, CH), 128.6 (s, CH), 133.0 (d,
J = 18.4 Hz, CH), 137.8 (d, J = 16.1 Hz, C), 142.0 (d, J = 7.5 Hz,
C), 155.6 (d, J = 1.7 Hz, C). 31P NMR (CDCl3, 121.5 MHz): d 5.8.
HRMS (ESI-TOF): m/z 446.0529 (M + H)+.
7.5 and 1.5 Hz, 1H), 6.99 (dd, J = 7.5 and 1.5 Hz, 1H), 7.22 (t,
J = 7.5 Hz, 1H). 13C NMR (CDCl3, 75.4 MHz): d 40.2 (CH2),
45.3 (CH3), 45.4 (CH3), 59.8 (CH2), 105.3 (C), 118.4 (CH), 125.0
(CH), 128.5 (CH), 144.9 (C), 155.6 (C). Anal. calc. for C12H19IN2:
C, 45.30; H, 6.02; N, 8.80%. Found: C, 45.37; H, 5.94; N, 8.68%.
2-Iodo-3-(1H-1,2,4-triazol-1-ylmethyl)-N,N -dimethylaniline
(3a). To a solution of 3-(dimethylamino)-2-iodobenzyl chloride
(180 mg, 0.61 mmol) in acetonitrile (10 mL) was added 1,2,4-
triazole sodium salt (124 mg, 1.36 mmol). The mixture was stirred
at 50 ◦C for 5 h. The solvent was evaporated and the residue
was partitioned between saturated aqueous NaHCO3 solution and
dichloromethane. The organic layer was washed with brine, dried,
and concentrated. The residue was purified by chromatography
(SiO2, from CH2Cl2 to CH2Cl2–MeOH 1%) to give triazole 3a
(138 mg, 69%). 1H NMR (CDCl3, 300 MHz): d 2.74 (s, 6H), 5.49
(s, 2H), 6.76 (dd, J = 7.8 and 1.5 Hz, 1H), 7.09 (dd, J = 8.1 and
1.5 Hz, 1H), 7.28 (dd, J = 8.1 and 7.8 Hz, 1H), 7.99 (s, 1H), 8.18
(s, 1H). 13C NMR (CDCl3, 75.4 MHz): d 45.2 (CH3), 59.3 (CH2),
103.2 (C), 120.8 (CH), 124.7 (CH), 129.2 (CH), 138.9 (C), 143.7
(CH), 152.0 (CH), 156.1 (C). Anal. calc. for C11H13IN4: C, 40.26;
H, 3.99; N, 17.07%. Found: C, 40.33; H, 3.86; N, 16.93%.
[3-(Dimethylamino)-2-iodophenyl]acetonitrile. A mixture of 3-
(dimethylamino)-2-iodobenzyl chloride (425 mg, 1.44 mmol) and
NaCN (78 mg) in DMSO was stirred at 80 ◦C overnight. The
mixture was diluted with Et2O and washed with brine. The
organic layer was dried and concentrated. The residue was purified
by chromatography (SiO2, CH2Cl2) to give [3-(dimethylamino)-
2-iodophenyl]acetonitrile (250 mg, 61%). 1H NMR (CDCl3,
300 MHz): d 2.75 (s, 6H), 3.90 (s, 2H), 7.08 (dd, J = 7.5 and
1.5 Hz, 1H), 7.26 (dd, J = 7.5 and 1.5 Hz, 1H), 7.34 (t, J = 7.5 Hz,
1H). 13C NMR (CDCl3, 75.4 MHz): d 31.6 (CH2), 45.1 (CH3),
103.6 (C), 117.5 (C), 120.3 (CH), 124.2 (CH), 129.3 (CH), 135.0
(C), 156.3 (C).
2-Iodo-3-(pyrazol-1-ylmethyl)-N,N-dimethylaniline (3b).
A
mixture of 3-(dimethylamino)-2-iodobenzyl chloride (250 mg,
0.86 mmol), pyrazole (88 mg, 1.3 mmol), and NaI (142 mg,
0.95 mmol) in acetone (10 mL) was stirred at reflux for 5 h. The
solvent was evaporated and the residue was partitioned between
saturated aqueous NaHCO3 solution and dichloromethane. The
organic layer was washed with brine, dried, and concentrated.
The residue was purified by chromatography (SiO2, from CH2Cl2
2-[3-(Dimethylamino)-2-iodophenyl]ethylamine. To
a
solu-
tion of [3-(dimethylamino)-2-iodophenyl]acetonitrile (250 mg,
0.87 mmol) in THF (6 mL) at 0 ◦C was added dropwise a
1 M solution of BH3·THF in THF (4.37 mL, 4.37 mmol), and
was stirred ◦at room temperature for 24 h. The mixture was
cooled to 0 C, and 6 M HCl (0.5 mL) was added. The mixture
was then made basic with 1 M NaOH solution and extracted
with dichloromethane. The organic layer was washed with water,
dried, and then concentrated to give 2-[3-(dimethylamino)-2-
iodophenyl]ethylamine (255 mg, quantitative), which was used in
the next step without purification. 1H NMR (CDCl3, 300 MHz): d
1
to CH2Cl2–MeOH 1%) to give pyrazole 3b (190 mg, 68%). H
NMR (CDCl3, 300 MHz): d 2.74 (s, 6H), 5.45 (s, 2H), 6.31 (t, J =
2.1 Hz, 1H), 6.47 (dm, J = 7.5 Hz, 1H), 7.04 (dd, J = 7.8 and
1.5 Hz, 1H), 7.21 (dd, J = 7.8 and 7.5 Hz, 1H), 7.48 (dd, J = 2.1
and 0.6 Hz, 1H), 7.59 (dd, J = 2.1 and 0.6 Hz, 1H). 13C NMR
(CDCl3, 75.4 MHz): d 45.2 (CH3), 61.6 (CH2), 102.3 (C), 105.8
(CH), 120.1 (CH), 123.8 (CH), 129.0 (CH), 129.9 (CH), 139.6
(CH), 141.1 (C), 155.6 (C). Anal. calc. for C12H14IN3: C, 44.05; H,
4.31; N, 12.84%. Found: C, 43.71; H, 4.47; N, 12.39%.
2.73 (s, 8H), 2.98 (s, 2H), 6.98 (m, 2H), 7.21 (t, J = 7.5 Hz, 1H). 13
C
NMR (CDCl3, 75.4 MHz): d 42.1 (CH2), 45.4 (CH3), 45.6 (CH2),
105.4 (C), 118.7 (CH), 125.3 (CH), 128.5 (CH), 144.0 (C), 155.7
(C).
Synthesis of palladium complexes
3-[2-(Dimethylamino)ethyl]-2-iodo-N,N-dimethylaniline
(2).
[OCP]PdI complex 4. To a solution of iodoaniline 1 (25 mg,
0.056 mmol) in dry benzene (5 mL) were added PPh3 (15 mg,
0.056 mmol) and Pd2(dba)3 (31 mg, 0.034 mmol). The solution
was stirred at room temperature under an open atmosphere for
22 h. The reaction mixture was filtered through Celite, washing
carefully with benzene. The filtrate was evaporated to dryness
to give a residue that was purified by chromatography (SiO2,
from CH2Cl2 to CH2Cl2–MeOH 4%) to give 4 as a brown solid.
Yield: 15 mg, 47%. Single crystals of complex 4 were grown by
slowly evaporating a dichloromethane solution. Mp: 210–213 ◦C.
mmax/cm−1 (KBr) 1628 (CO). 1H NMR (CD2Cl2, 300 MHz): d 3.52
(s, 3H), 3.94 (d, J = 12.6 Hz, 2H), 7.02 (m, 1H), 7.12–7.20 (m, 2H);
To a solution of 2-[3-(dimethylamino)-2-iodophenyl]ethylamine
(255 mg, 0.87 mmol) in acetonitrile (5 mL) were added a 37%
aqueous solution of formaldehyde (1.43 mL), NaBH3CN (273 mg,
4.35 mmol), and acetic acid (0.22 mL, 3.92 mmol). The mixture
was stirred at room temperature for 2 h, then acetic acid (0.22 mL,
3.92 mmol) was added, and the stirring was maintained for
30 min. The reaction mixture was diluted with dichloromethane
and water, and was made basic with 2 M NaOH. The organic
layer was concentrated; the residue was dissolved in a mixture
of MeOH (5 mL) and 2 M NaOH (5 mL), and was refluxed
overnight. The solvent was removed in vacuo, the residue was
dissolved in dichloromethane and washed with water. The organic
layer was dried and concentrated. The residue was purified by
chromatography (SiO2, from CH2Cl2 to CH2Cl2–MeOH 10%) to
give amine 2 (165 mg, 60%). 1H NMR (CDCl3, 300 MHz): d 2.37
(s, 6H), 2.55 (m, 2H), 2.73 (s, 6H), 3.03 (m, 2H), 6.95 (dd, J =
7.32–7.46 (m, 6H), 7.73–7.82 (m, 4H), 8.24 (d, J = 12 Hz, 1H). 13
C
NMR (CD2Cl2, 75.4 MHz): d 39.2 (CH3), 46.0 (d, J = 35.7 Hz,
CH2), 113.8 (CH), 122.2 (d, J = 23.1 Hz, CH), 126.5 (CH), 128.7
(d, J = 11.5 Hz, CH), 131.4 (d, J = 2.9 Hz, CH), 131.4 (d, J =
54.7 Hz, C), 133.5 (d, J = 10.9 Hz, CH), 136.9 (C), 148.7 (d,
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J = 15.5 Hz, C), 159.6 (CH). One C was not observed. 31P NMR
(CDCl3, 121.5 MHz): d 56.7. Anal. calc. for C21H19INOPPd: C,
44.59; H, 3.39; N, 2.48%. Found: C, 44.45; H, 3.54; N, 2.36%.
7.16–7.52 (m, 15H), 8.28 (s, 1H), 8.66 (s, 1H). 13C NMR (CDCl3,
75.4 MHz): d 46.9 (broad, CH3), 57.8 (CH2), 118.5 (CH), 120.2
(CH), 125.1 (CH), 127.4 (d, J = 10.9 Hz, CH), 129.8 (d, J =
2.3 Hz, CH), 132.6 (d, J = 52.4 Hz, C), 134.5 (d, J = 10.9 Hz,
CH), 135.8 (C), 143.0 (CH), 151.3 (d, J = 5.7 Hz, C), 155.8 (CH),
157.3 (d, J = 4.6 Hz, C). 31P NMR (CDCl3, 121.5 MHz): d 32.8.
Anal. calc. for C29H28IN4PPd: C, 49.98; H, 4.05; N, 8.04%. Found:
C, 50.19; H, 4.08; N, 7.63%.
[CCN]-Palladium pincer complex 5. To a solution of iodoani-
line 2 (20 mg, 0.063 mmol) in dry benzene (5 mL) were added
PPh3 (16 mg, 0.06 mmol) and Pd2(dba)3 (35 mg, 0.038 mmol).
The solution was stirred at room temperature under an open
atmosphere for 24 h. The solvent was removed in vacuo and the
residue was triturated with diethyl ether. The mixture was filtered
through Celite, washing carefully with diethyl ether. The ether
filtrate was discarded, and then the washing was continued with
dichloromethane. The dichloromethane filtrate was evaporated to
dryness to give a residue that was purified by chromatography
(SiO2, CH2Cl2) to give 5 as a yellow solid. Yield: 17 mg, 85%.
Single crystals of complex 5 were grown by slowly evaporating a
dichloromethane–diethyl ether solution. Mp: 146 ◦C (decomp.).
mmax/cm−1 (KBr) 1543 (CO). 1H NMR (CDCl3, 300 MHz): d 2.67
(s, 6H), 2.72 (dd, J = 5.7 and 5.4 Hz, 2H), 2.95 (dd, J = 5.7 and
5.4 Hz, 2H), 3.03 (s, 3H), 6.49 (dd, J = 7.5 and 1 Hz, 1H), 6.54
(d, J = 7.5 Hz, 1H), 6.97 (t, J = 7.5 Hz, 1H). 13C NMR (CDCl3,
75.4 MHz): d 26.9 (CH3), 33.9 (CH2), 47.9 (CH3), 63.2 (CH2),
106.8 (CH), 120.1 (CH), 124.6 (CH), 141.9 (C), 153.4 (C), 207.7
(C). One C was not observed. Anal. calc. for C24H32N4O2Pd2: C,
46.39; H, 5.19; N, 9.02%. Found: C, 46.34; H, 5.19; N, 8.88%.
Azapalladacycle 6b. Using the same procedure as for the syn-
thesis of 6a and starting from iodoaniline 3b (25 mg, 0.076 mmol),
palladium complex 6b was obtained as a white solid after
purification by chromatography (SiO2, from hexane to hexane–
EtOAc 40%). Yield: 40 mg, 75%. 1H NMR (CDCl3, 400 MHz): d
2.66 (broad s, 6H), 5.03 (d, J = 13.6 Hz, 1H), 5.93 (d, J = 13.6 Hz,
1H), 6.06 (dt, J = 7.6 and 1.6 Hz, 1H), 6.24 (m, 1H), 6.70 (dd, J =
7.6 and 1.2 Hz, 1H), 6.77 (t, J = 7.6 Hz, 1H), 7.15–7.35 (m, 9H),
7.45 (broad, 6H), 7.56 (d, J = 2.4 Hz. 1H), 8.25 (d, J = 1.6 Hz,
1H). 13C NMR (CDCl3, 75.4 MHz): d 46.6 (broad, CH3), 60.5
(CH2), 106.3 (d, J = 3.5 Hz, CH), 117.9 (CH), 119.8 (CH), 124.6
(CH), 127.3 (d, J = 10.3 Hz, CH), 129.6 (CH), 130.5 (CH), 133.0
(d, J = 51.8 Hz, C), 134.5 (d, J = 10.3 Hz, CH), 137.3 (C), 144.6
(CH), 151.6 (d, J = 5.2 Hz, C), 157.1 (d, J = 4.6 Hz, C). 31P NMR
(CDCl3, 121.5 MHz): d 31.7. Anal. calc. for C30H29IN3PPd·EtOAc:
C, 52.13; H, 4.76; N, 5.36%. Found: C, 52.59; H, 4.72; N, 5.57%.
1-[3-(Methylamino)benzyl]-1,2,4-triazole (7). Using the same
procedure as for the synthesis of 6a, but without the addition
of PPh3, aniline 7 was obtained as an oil after purification by
chromatography (SiO2, from CH2Cl2 to CH2Cl2–MeOH 10%).
Azapalladacycle 6a. To a solution of iodoaniline 3a (21 mg,
0.064 mmol) in dry benzene (5 mL) were added PPh3 (17 mg,
0.064 mmol) and Pd2(dba)3 (35 mg, 0.038 mmol). The solution
was stirred at room temperature under an argon atmosphere for
20 h. The reaction mixture was filtered through Celite, washing
carefully with benzene. The filtrate was evaporated to dryness to
give a residue that was purified by chromatography (SiO2, from
CH2Cl2 to CH2Cl2–MeOH 1%) to give 6a as a white solid. Yield:
30 mg, 67%. 1H NMR (CDCl3, 200 MHz): d 2.66 (s, 6H), 5.22 (d,
J = 13.4 Hz, 1H), 5.88 (d, J = 13.4 Hz, 1H), 6.12 (broad d, J =
7.8 Hz, 1H), 6.73 (d, J = 7.8 Hz, 1H), 6.81 (t, J = 7.8 Hz, 1H),
1
Yield: 7 mg, 47%. H NMR (CDCl3, 300 MHz): d 2.81 (s, 3H),
3.80 (broad, 1H), 5.26 (s, 2H), 6.46 (broad s, 1H), 6.55–6.61 (m,
2H), 7.18 (t, J = 7.8 Hz, 1H), 7.96 (s, 1H), 8.04 (s, 1H). HRMS
(ESI-TOF): m/z 189.1126 (M + H)+.
Azapalladacycle 8. To a solution of palladium complex 6a
(34 mg, 0.049 mmol) in dry THF (10 mL) was added Tl(TfO)
(19 mg, 0.054 mmol). The mixture was stirred at room temperature
Table 1 Selected crystallographic data for complexes 4, 5, and 8·CH2Cl2·3CH3OH·5H2O
4
5
8·CH2Cl2·3CH3OH·5H2O
Formula
Mr
C21H19INOPPd
565.64
Monoclinic
C24H32N4O2Pd2
621.34
Orthorhombic
C124H136Cl2F12N16O20P4Pd4S4
3147.22
Triclinic
¯
P1
Crystal system
Space group
P21/c
Pbca
˚
a/A
10.477(4)
10.940(3)
18.559(3)
90
106.32(2)
90
2041.5(10)
4
1.840
7.688(5)
11.928(7)
25.540(8)
90
90
90
2342(2)
4
1.762
14.493(4)
14.905(2)
33.266(7)
90.80(2)
96.83(2)
91.37(2)
7132(3)
2
1.464
3198
0.21 × 0.15 × 0.1
2.58–32.34
72516
37777 (0.0437)
0.0777
˚
b/A
˚
c/A
a/◦
b/◦
c /◦
3
˚
V/A
Z
Dc/Mg m−3
F(000)
1096
1248
Crystal size/mm
0.2 × 0.1 × 0.1
3.46–30.00
19826
5467 (0.0324)
0.0338
0.0882
1.239
0.2 × 0.1 × 0.1
3.09–28.51
1741
1741 (0.0570)
0.0539
0.1261
1.219
h range/◦
Reflections collected
Independent reflections (Rint
R1 [I>2r(I)]
)
wR2 [I>2r(I)]
0.2372
1.028
Goodness-of-fit on F2
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for 24 h. A pale yellow precipitate formed that was collected by
filtration and then triturated with MeOH. The resulting solid was
filtered off and dried to give 8 as a yellow solid. Yield: 21 mg, 60%.
Single crystals of complex 8 were grown by slowly evaporating
a dichloromethane–diethyl ether–MeOH solution under an open
conducted to establish the mechanisms of the activation/oxidation
sequences observed.
Acknowledgements
1
This work was supported by MEC (Spain)-FEDER (Project
atmosphere. Mp: decomposition of the crystal when heating. H
CTQ2004-04701/BQU)
2005SGR-00442). D. S. thanks the DURSI for “Distincio´
per a la Promocio´ de la Recerca Universita`ria”.
and
DURSI-Catalonia
(Grant
NMR (CDCl3, 400 MHz): d 2.45 (broad, 6H), 5.21 (d, J = 14.4 Hz,
1H), 6.15 (d, J = 14.4 Hz, 1H), 6.17 (d, J = 6 Hz, 1H), 6.89 (d, J =
7.2 Hz, 1H), 6.95–7.10 (m, 10H), 7.26–7.32 (m, 6H), 7.76 (s, 1H),
8.41 (s, 1H). 13C NMR (CDCl3, 100 MHz): d 41.0 (broad, CH3),
58.8 (CH2), 119.2 (CH), 122.8 (CH), 125.3 (CH), 128.7 (d, J =
10.1 Hz, CH), 128.9 (d, J = 55.0 Hz, C), 131.0 (CH), 132.8 (d, J =
10.9 Hz, CH), 136.3 (C), 140.6 (C), 144.5 (CH), 150.7 (C), 157.4
(CH). 31P NMR (CDCl3, 121.5 MHz): d 28.6. HRMS (ESI-TOF):
m/z 569.1090 (M)+.
Notes and references
1 M. Albrecht and G. van Koten, Angew. Chem., Int. Ed., 2001, 40, 3751–
3781; J. T. Singleton, Tetrahedron, 2003, 59, 1837–1857; J. Dupont, C. S.
Consorti and J. Spencer, Chem. Rev., 2005, 105, 2527–2572.
2 See, for example: B. Rybtchinski, S. Oevers, M. Montag, A. Vigalok,
H. Rozenberg, J. M. L. Martin and D. Milstein, J. Am. Chem. Soc.,
2001, 123, 9064–9077; E. Poverenov, M. Gandelman, L. J. W. Shimon,
H. Rozenberg, Y. Ben-David and D. Milstein, Chem.–Eur. J., 2004,
10, 4673–4684; E. Poverenov, M. Gandelman, L. J. W. Shimon, H.
Rozenberg, Y. Ben-David and D. Milstein, Organometallics, 2005, 24,
1082–1090; E. Poverenov, G. Leitus, L. J. W. Shimon and D. Milstein,
Organometallics, 2005, 24, 5937–5944; J. Fischer, M. Schu¨rmann, M.
Mehring, U. Zachwieja and K. Jurkschat, Organometallics, 2006, 25,
2886–2893 and references therein.
3 D. Sole´, S. D´ıaz, X. Solans and M. Font-Bardia, Organometallics, 2006,
25, 1995–2001.
4 D. Sole´, L. Vallverdu´, X. Solans and M. Font-Bardia, Chem. Commun.,
2005, 2738–2740.
5 J. M. Longmire, X. Zhang and M. Shang, Organometallics, 1998, 17,
4374–4379.
X-Ray crystallography
Intensities for complexes 4, 5, and 8·CH2Cl2·3CH3OH·5H2O
were collected with a MAR345 diffractometer. The structures
were solved by direct methods, using the SHELXS97 computer
program. All the structures were refined by full-matrix least-
squares methods with the SHELXL97 computer program.13
A
summary of the crystallographic data and refinement parameters
for 4, 5, and 8·CH2Cl2·3CH3OH·5H2O is given in Table 1.
ORTEP14 plots for complexes 4, 5, and the cation of 8 are shown
in Fig. 1–3, respectively.
6 For a related C–H activation process, see: J. A. M. Brandts, E.
Kruiswijk, J. Boersma, A. L. Spek and G. van Koten, J. Organomet.
Chem., 1999, 585, 93–99.
Conclusions
7 For 1,2,4-triazole-based pincer complexes, see: (a) E. D´ıez-Barra, J.
Guerra, I. Lo´pez-Solera, S. Merino, J. Rodr´ıguez-Lo´pez, P. Sa´nchez-
Verdu´ and J. Tejeda, Organometallics, 2003, 22, 541–547; (b) E. D´ıez-
Barra, J. Guerra, V. Hornillos, S. Merino and J. Tejeda, Organometallics,
2003, 22, 4610–4612.
8 For pyrazole-based pincer complexes, see: (a) C. M. Hartshorn and P. J.
Steel, Organometallics, 1998, 17, 3487–3496; (b) H. P. Dijkstra, M. D.
Meijer, J. Patel, R. Kreiter, G. P. M. van Klink, M. Lutz, A. L. Spek,
A. J. Canty and G. van Koten, Organometallics, 2001, 20, 3159–3168;
(c) F. Churruca, R. SanMart´ın, I. Tellitu and E. Dom´ınguez, Synlett,
2005, 3116–3120.
The N,N-dimethyl-2-iodoanilines with chelating “arms” at the 3-
position have proved to be a versatile source of Pd(II) complexes
when reacting with Pd2(dba)3. The nature of the complex obtained
strongly depends on the type of chelating “arm”. Thus, from
iodoanilines bearing –CH2PR2 and –CH2NR2 units, [OCL]PdI
complexes (L = P, N respectively) were obtained by means of a
sequential C(sp3)–H activation/oxidation process at the a-position
of the aniline N atom. On the other hand, the iodoaniline with
the long “arm” –CH2CH2NR2 afforded a [CCN]Pd complex,
resulting from a multistep process in which a new C–H activation
reaction takes place after the initial C(sp3)–H activation/oxidation
sequence. Finally, the iodoanilines based on triazole and pyrazole
“arms” afforded simple 6-membered azapalladacycles in which
the aniline N is merely a spectator. From the results obtained
in this work and in previous studies we can conclude that
the four-membered cyclopalladated framework cannot fit into
stable [NCL]PdI pincer complexes. Further investigation will be
9 J. Dupont, M. Pfeffer, J. C. Daran and Y. Jeannin, Organometallics,
1987, 6, 899–901 and references therein.
10 K. Hosoi, K. Nozaki and T. Hiyama, Org. Lett., 2002, 4, 2849–2851.
11 The C–H activation reaction probably involves the formation of an
organopalladium(IV) complex intermediate. A. J. Canty, Acc. Chem.
Res., 1992, 25, 83–90.
12 K. Koerber-Ple´ and G. Massiot, Synlett, 1994, 759–760.
13 G. M. Sheldrick, SHELXS97 and SHELXL97, University of
Go¨ttingen, Go¨ttingen, Germany, 1997.
14 ORTEP drawings were generated by ORTEP-3 1.074.L. J. Farrugia,
J. Appl. Crystallogr., 1997, 30, 565.
4292 | Dalton Trans., 2007, 4286–4292
This journal is
The Royal Society of Chemistry 2007
©