Nucleophilic additions of methanol to the dichloropalladium(II) complex with C-(2-pyridyl)-N-methylnitrone

Article abstract of DOI:10.1515/znb-2006-1108

The additions of methanol to the dichloropalladium(II) complex with C-(2-pyridyl)-N-methylnitrone led to the formation of the Pd(II)-coordinated α-methoxy-α-(2-pyridyl)-N,N-dimethylhydroxylamine. It has been demonstrated that the Pd(II) complexation is es

Full text of DOI:10.1515/znb-2006-1108

Nucleophilic Additions of Methanol to the Dichloropalladium(II) Complex
with C-(2-Pyridyl)-N-methylnitrone
Roman O. Doroschuka, Elena G. Petkovaa, Rostislav D. Lampekaa,
Konstantin V. Domasevitcha, and Marian V. Gorichkob
a Department of Inorganic Chemistry, Kiev University, Volodimirska St. 64, Kiev 01033, Ukraine
b Department of Organic Chemistry, Kiev University, Volodimirska St. 64, Kiev 01033, Ukraine
Reprint requests to Dr. R. D. Lampeka. E-mail: r.lampeka@clariant.com.ua
Z. Naturforsch. 61b, 1361 – 1364 (2006); received March 22, 2006
The additions of methanol to the dichloropalladium(II) complex with C-(2-pyridyl)-N-
methylnitrone led to the formation of the Pd(II)-coordinated α-methoxy-α-(2-pyridyl)-N,N-
dimethylhydroxylamine. It has been demonstrated that the Pd(II) complexation is essential for the
stabilization of α-alkoxyhydroxylamines.
Key words: Nitrones, Palladium, α-Alkoxyhydroxylamine Complexes
Introduction
Nitrones are important starting compounds in nu-
merous organic syntheses, in particular for 1,3-
dipolar cycloadditions with unsaturated compounds
and for nucleophilic additions to the azomethine-N-
oxide group [1]. Both reactions can be performed
in asymmetric variants and provide synthetic access
to structurally diverse natural products [2]. Thus, the
catalytic asymmetric 1,3-dipolar cycloadditions of ni-
trones and alkenes afford the enantio- or diastereomers
of isoxazolidines which can be readily reduced to γ-
aminoalcohols [3]. This approach was used in syn-
theses of 4-hydroxypyroglutamic acid and its alde-
hyde, which involves N-O bond reduction followed
by intramolecular cyclization [4]. Nucleophilic addi-
tions of Grignard reagents to nitrones were employed
in asymmetric syntheses of N-hydroxy-α-aminoacids,
protected N-hydroxy-α-aminoaldehydes [5] as well
as α-hydroxy-β-amino acids [6]. The nitrone oxygen
atom can coordinate to a metal ion or another Lewis
acid, which results in a lowering of the LUMOnitrone
energy that alleviates the 1,3-dipolar cycloadditions
with electron-rich alkenes [7] and lowers the reactiv-
ity of nitrones in cycloadditions with electron-deficient
alkenes [8]. Polarization of the azomethine-N-oxide
group by coordination of nitrones leads to the activa-
tion of nitrones for nucleophilic additions. In spite of
Scheme 1.
until recently little effort has been devoted to investiga-
tions of nitrone complexes [9].
Results and Discussion
Following our studies on heteroaromatic nitrone
ligands [10] we have prepared a PdCl2 complex
with C-(2-pyridyl)-N-methylnitrone (L). Reaction of
the ligand and Na2PdCl4 in acetonitrile solution im-
mediately yields a yellow microcrystalline precip-
itate of Pd(L)Cl2 (1), the composition of which
was established by elemental analysis and IR spec-
troscopy. Complex 1 is insoluble in common or-
ganic solvents, while it slowly reacts with alco-
hols. It was found that by treatment with methanol
the compound 1 undergoes nucleophilic addition
of methanol to give the α-methoxy-α-(2-pyridyl)-
N,N-dimethylhydroxylamine complex 2, as shown in
Scheme 1.
The X-ray crystal structure of 2 is shown in Fig. 1.
the apparent connection between coordinative proper- The complex 2 adopts a molecular structure with the
ties of nitrones and their reactivity in organic reactions, expected planar four-fold coordination of the palla-
0932–0776 / 06 / 1100–1361 $ 06.00 © 2006 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com
Unauthenticated
Download Date | 3/3/17 1:02 PM

1362
R. O. Doroschuk et al. · Nucleophilic Additions of Methanol to the Dichloropalladium(II) Complex
Scheme 2.
and methanol have been released. The authors of pre-
vious work [11] proposed to explain the rapid Z-E
isomerization of C-aryl-N-alkylnitrones proceeding in
CD3OD solution in the presence of CD3ONa in terms
of reversible addition-elimination reactions of MeOH
at/from the C=N double bond (Scheme 2).
The thermodynamic equilibrium of this reaction is
substantially shifted to the nitrone forms, which was
1
proved by H NMR and UV spectroscopy data [11].
Therefore, it can be concluded, that the complexation
with Pd(II) cation changes the equilibrium in favor of
hydroxylamines.
1
The H NMR spectrum of 2 in CD3CN shows res-
onances of methoxy and hydroxy groups. There is a
large upfield shift (1.6 ppm) of the signal of the pro-
ton Ha bound to the chiral carbon atom, and a down-
1
field shift of the 3-pyridine proton signal. The H NMR
spectra of the adducts with EtOH and PrOH exhibit
two different signals for the O-CH2 diastereotopic pro-
tons.
Fig. 1. Molecular structure of the palladium complex 2 with
the displacement ellipsoids drawn at 50% probability level.
Selected bond lengths and angles: Pd(1)-N(1) 2.016(2),
Pd(1)-N(2) 2.043(2), Pd(1)-Cl(1) 2.2914(8), Pd(1)-Cl(2)
˚
2.2964(7), N(2)-O(2) 1.438(2) A; Cl(1)-Pd(1)-Cl(2)
92.43(3), N(1)-Pd(1)-N(2) 81.01(7)◦.
The nitrogen atom of the hydroxylamino group co-
ordinated to the palladium atom becomes the second
chiral center in molecule 2. Therefore, the molecule 2
and other adducts with alcohols may exist as two di-
astereomers having the hydroxy and alkoxy groups ei-
ther in cis or in trans position. The 1H NMR spec-
trum reveals that in the reaction outlined in Scheme 1
only a single diastereomer is formed, and the trans-
position of oxygen containing groups can be assigned
from X-ray structure data. The structure investigation
of 2 in CD3CN solution by NOE-experiments unfortu-
nately did not give unambiguous results.
dium ion. The environment of the metal centre com-
prises two nitrogen donors of the organic chelate
˚
(Pd(1)–N(1) 2.016(2), Pd(1)-N(2) 2.043(2) A) and
two cis-situated chloride ions (Pd-Cl 2.2914(8) and
˚
2.2964(7) A). The chelate cycle is not planar and has
an envelope conformation as the hydroxylamine nitro-
˚
gen atom deviates from the mean plane by 0.70 A.
Weaker intramolecular interactions are important for
stabilization of the ligand conformation. Thus, the hy-
droxy group forms a hydrogen bond to the cis-chloride
◦
˚
ligand (O(2)---Cl(2) 3.01 A, ∠ O(2)H(1)Cl(2) 152 ).
Palladium complexes with oxygen donors are not
very stable, although there is a number of complexes
with bidentate ligands containing along with oxygen
binding group also soft donor atoms such as N, P, S,
Se [12]. Since oxygen has a much lower affinity to pal-
ladium in comparison with nitrogen, we believe that
the change of coordination mode from N,O-chelation
in 1 to N,N-chelation in 2 is one of the driving forces
that brings about the alcohol addition. The consider-
able increase of reactivity of the azomethine group in 1
toward the nucleophilic reagents can be explained by
Analogous addition reactions proceed in high yield
by refluxing 1 not only in methanol, but also in EtOH,
PrOH, i-PrOH. Complex 1 dissolves within 3 h, and
after evaporation of the alcohols the corresponding
α-alkoxyhydroxylamine complexes remain as red or-
ange solids. All the resultant compounds are stable in
solid state in air and also in solutions. Our attempts to
obtain adducts of this type with phenols and amines
failed, and only unchanged starting materials were re-
covered.
By treatment of complex 2 with ethylenediamine the electron withdrawing effect of the PdCl2 moiety.
in acetonitrile solution only the starting nitrone L Moreover, the palladium atom coordinates the nitrogen
Unauthenticated
Download Date | 3/3/17 1:02 PM

R. O. Doroschuk et al. · Nucleophilic Additions of Methanol to the Dichloropalladium(II) Complex
1363
Table 1. Crystal and refinement data for palladium com-
plex 2.
Formula
C8H12Cl2N2O2Pd
345.50
Formula weight
Crystal system
Space group, Z
Unit cell dimensions (A, ◦) a,α
b,β
triclinic
¯
P1,2
˚
7.9624(9), 111.70(2)
9.0266(8), 110.30(2)
9.611(2), 94.753(8)
584.0(1)
c,γ
3
˚
V, A
Dcalc (g cm−3
)
1.965
F(000)
340
20.27
53.4
2560
2412 (0.015)
184
1.114
0.019, 0.052
0.021, 0.052
0.64, −0.73
µ(MoKα ) cm−1
Scheme 3.
2θmax (deg)
of the hydroxylamino group in 2, thereby stabilizing
the α-methoxyhydroxylamine.
In order to explain the formation of the trans-
diastereomer 2 we propose the mechanism outlined in
Scheme 3: 1) Nucleophilic addition of methanol to the
double bond of compound 1 requires the antiperiplanar
alignment of the methoxy group and the lone pair of
Reflections measured
Unique reflections (Rint
Parameters refined
GOF on F2
)
R1,wR2 [I ≥ 2σ(I)]
R1,wR2 [all data]
−3
˚
Max. peak and hole, e A
nitrogen atom, and the intermediate A forms initially. 3J5−4 = 7.6 Hz, 3J5−6 = 4.8 Hz, 4J5−3 = 0.8 Hz, 1 H, 5-H),
7.76 (s, 1 H, nitrone CH), 7.82 (td, 3J4−3 =3 J4−5 = 7.6 Hz,
2) Owing to the low inversion barrier at the tetrahedral
nitrogen atom, the configuration inversion of the nitro-
gen atom should proceed with formation of the inter-
mediate B. 3) Because of the steric repulsion between
the methyl and methoxy groups, which are the most
bulky substituents in the chelate ring, the intermedi-
ate B should be more stable than A. 4) Final step is
4J4−6 = 1.2 Hz, 1 H, 4-H), 8.62 (dd, J6−5 = 4.8 Hz,
3
4J6−4 = 1.2 Hz, 1 H, 6-H), 9.04 (dd, J3−4 = 7.6 Hz,
3
4J3−5 = 0.8 Hz, 1 H, 3-H). – 13C{ H} NMR (100.70 MHz,
1
CD3CN): δ = 54.8, 123.2, 124.7, 136.4, 137.3, 150.2, 150.4.
– C7H8N2O (136.2): calcd. C 61.75, H 5.92, N 20.57; found
C 61.81, H 5.93, N 20.52.
the rotation around the C-N bond with the simultane-
ous recoordination in the N,N- (instead of the N,O-)
Pd(L)Cl2 (1)
chelation mode.
Hot acetonitrile solutions of Na2PdCl4 (0.294 g, 1 mmol)
and C-(2-pyridyl)-N-methylnitrone (0.136 g, 1 mmol) were
combined. Yellow crystals of the product were formed
Experimental Section
Syntheses
immediately. The precipitate was filtered off and dried.
Yield 0.245 g (78%). – IR (KBr): ν = 1645, 1600
(C=N), 1170 (N-O) cm−1. – C7H8Cl2N2OPd (313.5): calcd.
C 26.82, H 2.57, N 8.94; found C 26.80, H 2.63, N 8.90.
All chemicals were commercial products of reagent grade,
used without further purification. The 1H and 13C NMR
spectra were recorded on a “Mercury 400” Varian (400 MHz)
spectrometer, and IR spectra were recorded on a Carl Zeiss
(Jena) UR-10 spectrometer (KBr pellets, 400 – 4000 cm−1).
Compound 2 [Pd(L)Cl2+CH3OH]
A mixture of 1 (0.157 g, 0.5 mmol) and 20 mL of
methanol was refluxed for 3 h. During this period the starting
C-(2-Pyridyl)-N-methylnitrone (L)
N-Methylhydroxylamine hydrochloride (8.770 g, compound dissolves slowly. After cooling, orange crystals
0.105 mol) was added in one portion to a stirred mixture of were formed (0.126 g, 78%). – IR (KBr): ν = 1610 (C=N),
Na2CO3 (21.198 g, 0.2 mol) and pyridine-2-carbaldehyde 1130 (N-O) cm−1. – 1H NMR (400.45 MHz, CD3CN): δ =
(10.711 g, 0.1 mol) in 250 mL of CH2Cl2. The resulting 2.90 (s, 3 H, NCH3), 3.95 (s, 3 H, OCH3), 6.13 (s, 1 H),
3
suspension was refluxed for 3 h, cooled and filtered, 7.56 – 7.64 (m, 2 H, 3-H, 5-H), 8.16 (td, J4−3 =3 J4−5
=
and the precipitate washed twice with CH2Cl2. The 8 Hz, 4J4−6 = 1.2 Hz, 1 H, 4-H), 8.70 (s, 1 H, OH), 8.85 (dd,
combined filtrates were evaporated at reduced pressure. 3J6−5 = 5.6 Hz, 4J6−4 = 1.2 Hz, 1 H, 6-H). – 13C{ H} NMR
1
After recrystallization from cyclohexane the product was (100.70 MHz, CD3CN): δ = 46.9, 63.2, 103.2, 125.6, 127.2,
obtained as white crystals (11.16 g, 82%). – 1H NMR 142.1, 150.0, 156.5. – C8H12Cl2N2O2Pd (345.5): calcd.
(400.45 MHz, CD3CN): δ = 3.85 (s, 3 H, CH3), 7.32 (ddd, C 27.81, H 3.50, N 8.11; found C 27.74, H 3.52, N 8.08.
Unauthenticated
Download Date | 3/3/17 1:02 PM

1364
R. O. Doroschuk et al. · Nucleophilic Additions of Methanol to the Dichloropalladium(II) Complex
Crystallography
ble 1). All hydrogen atoms were located and refined iso-
tropically.
Crystallographic data for the structure have been de-
posited with the Cambridge Crystallographic Data Centre,
CCDC-602325. Copies of the data can be obtained free of
charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data request/cif.
For complex 2, the unit cell dimensions and the intensi-
ties of the reflections were measured at r. t. using a CAD-
4 Enraf Nonius diffractometer. The structure was solved
by direct methods and refined in anisotropic approxima-
tion for all non-hydrogen atoms using SHELX-97 [13] (Ta-
[8] a) J. Tanaka, S. Kanemasa, Tetrahedron 57, 899 (2001);
b) S. Kanemasa, N. Ueno, M. Shirahase, Tetrahedron
Lett. 43, 657 (2002).
[1] K. B. G. Torssell, Nitrile Oxides, Nitrones, and Ni-
tronates in Organic Synthesis, p. 75 – 89, 129 – 255,
VCH, Weinheim (1988).
[9] a) F. A. Villamena, M. H. Dickman, De L. R. Crist, In-
org. Chem. 37, 1446 (1998); b) P. Merino, S. Anoro,
E. Cerrada, M. Laguna, A. Moreno, T. Tejero,
Molecules 6, 208 (2001).
[10] a) E. G. Petkova, K. V. Domasevitch, M. V. Gorichko,
R. D. Lampeka, V. Ya. Zub, Z. Naturforsch. 56b,
1264 (2001); b) E. G. Petkova, R. D. Lampeka, M. V.
Gorichko, K. V. Domasevitch, Polyhedron 20, 747
(2001).
[2] a) M. Frederickson, Tetrahedron 53, 403 (1997);
b) R. Pulz, S. Cicchi, A. Brandi, H. U. Reissig, Eur. J.
Org. Chem, 1153 (2003); c) P. Merino, S. Franco, D. La-
fuente, F. Merchan, J. Revuelta, T. Tejero, Eur. J. Org.
Chem. 2877 (2003).
[3] a) D. Basso, G. Broggini, D. Passarella, T. Pilati, A. Ter-
raneo, G. Zecchi, Tetrahedron 58, 4445 (2002); b) M. C.
Whisler, P. Beak, J. Org. Chem. 68, 1207 (2003);
c) A. Arnone, G. Broggini, D. Passarella, A. Terraneo,
G. Zecchi, J. Org. Chem. 63, 9279 (1998).
[4] a) P. Merino, S. Anoro, S. Franco, F. L. Merhan,
T. Tejero, V. Tunon J. Org. Chem. 65, 1590 (2000);
b) T. Tejero, A. Dondoni, I. Rojo, F. L. Merhan,
P. Merino, Tetrahedron 53, 3301 (1997).
[5] P. Merino, E. Castillo, S. Franco, F. L. Merhan,
T. Tejero, J. Org. Chem. 63, 2371 (1998).
[11] M. A. Voinov, B. A. Grigorjev, Izv. Akad. Nauk, Ser.
Khim. 283 (2002).
[12] a) C. A. Otter, D. A. Bardwell, S. M. Couchman, J. C.
Jeffery, J. P. Maher, M. D. Ward, Polyhedron 17, 211
(1998); b) J. Andrieu, P. Braunstein, F. Naud, R. D.
Adams, J. Organomet. Chem. 601, 43 (2000); c) M. V.
Esterhuysen, R. Brull, H. G. Raubenheimer, C. Ester-
huysen, G. J. Kruger, J. Organomet. Chem. 619, 164
(2001).
[6] P. Merino, E. Castillo, S. Franco, F. L. Merhan,
T. Tejero, Tetrahedron 54, 12301 (1998).
[13] G. M. Sheldrick, SHELXS97 and SHELXL97, The
programs for crystal structure solution and refinement.
University of Go¨ttingen, Germany (1997).
[7] a) J. P. G. Seerden, M. M. M. Boeren, H. W. Scheeren,
Tetrahedron 53, 11843 (1997); b) J. P. G. Seerden,
A. W. A. Scholte op Reimer, H. W. Scheeren, Tetrahe-
dron Lett. 35, 4419 (1994).
Unauthenticated
Download Date | 3/3/17 1:02 PM