PtII-mediated 1,3-dipolar cycloaddition of oxazoline N-oxides to nitriles as a key step to dihydrooxazolo-1,2,4-oxadiazoles

Article abstract of DOI:10.1021/ic701133b

A novel type of heterocycle, viz., 2,3a-disubstituted 5,6-dihydro-3aH-[1,3] oxazolo[3,2-b][1,2,4]oxadiazoles, was generated by an intermolecular Remediated 1,3-dipolar cycloaddition (1,3-DCA) between the oxazoline N-oxide C(Me) ₂CH₂OC(R)=N⁺(O^-) (R = Me, Et) and coordinated nitriles in the complexes trans/cis-[PtCl₂(R′CN) ₂] [R′ = Me, Et, CH₂Ph, Ph, N(C₅H ₁₀)]. The reaction is unknown for free RCN and oxazoline N-oxides, but under Remediated conditions, it proceeds smoothly (CH₂Cl ₂, 20-25°C, 18-20 h) and gives pure complexes [PtCl ₂{N=C(R′)ONC(R)OCH₂CMe₂}₂] [R/R′ = Me/Me, 1; Me/Et, 2; Me/CH₂Ph, 3; Me/Ph, 4; Me/N(C ₅H₁₀), 5; Et/Me, 6; Et/Et, 7; Et/CH₂Ph, 8; Et/Ph, 9; Et/N(C₅H₁₀), 10] in 42-84% yields after column chromatography. Compounds 1-10 were characterized by elemental analyses (C, H, N), FAB⁺-MS, IR, and ¹H and ¹³C{¹H} NMR spectroscopies, and X-ray diffraction (for 1, 2, 5, and 9). With the exception of benzonitrile complexes, 1,3-DCA of oxazoline N-oxides to the Pt^II-ligated nitriles occurred diastereoselectively and afforded mixtures of enantiomers. Depending on the substituents on nitriles, asymmetric atoms in both of the formed heterocyclic ligands have the same (SS/ RR) or different (SR/RS) configurations. The heterocyclic ligands were liberated from 1-4 and 6-9 by treatment with excess ethane-1,2-diamine (en) in CH ₂Cl₂ for 1 day at 20-25°C (for R′ = Me, Et, CH₂Ph) and at 50°C (for R′ = Ph) to achieve the free organic species and the well-known [Pt(en)₂](Cl)₂; the products were separated, and 2,3a-disubstituted 5,6-dihydro-3aH-[1,3]oxazolo[3, 2-b][1,2,4]oxadiazoles (11-18) were characterized by ESI⁺-MS and ¹H and ¹³C{¹H} NMR spectroscopies.

Full text of DOI:10.1021/ic701133b

Inorg. Chem. 2007, 46, 8323−8331
PtII-Mediated 1,3-Dipolar Cycloaddition of Oxazoline N-Oxides to Nitriles
as a Key Step to Dihydrooxazolo-1,2,4-oxadiazoles
Anastassiya V. Makarycheva-Mikhailova,‡ Julia A. Golenetskaya,‡ Nadezhda A. Bokach,‡
Irina A. Balova,‡ Matti Haukka,† and Vadim Yu. Kukushkin*,‡
Department of Chemistry, St. Petersburg State UniVersity, 198504 Stary Petergof,
Russian Federation, and Department of Chemistry, UniVersity of Joensuu, P.O. Box 111,
FI-80101 Joensuu, Finland
Received June 9, 2007
A novel type of heterocycle, viz., 2,3a-disubstituted 5,6-dihydro-3aH-[1,3]oxazolo[3,2-b][1,2,4]oxadiazoles, was
generated by an intermolecular PtII-mediated 1,3-dipolar cycloaddition (1,3-DCA) between the oxazoline N-oxide
+
C(Me)2CH2OC(R)
d
N (O-) (R
)
Me, Et) and coordinated nitriles in the complexes trans/cis-[PtCl2(R
′
CN)2] [R′ )
Me, Et, CH2Ph, Ph, N(C5H10)]. The reaction is unknown for free RCN and oxazoline N-oxides, but under
PtII-mediated conditions, it proceeds smoothly (CH2Cl2, 20
−
25 C, 18 20 h) and gives pure complexes
°
−
[PtCl2
Me, 6; Et/Et, 7; Et/CH2Ph, 8; Et/Ph, 9; Et/N(C5H10), 10] in 42
10 were characterized by elemental analyses (C, H, N), FAB+-MS, IR, and 1H and 13
C{ }
{N
d
C(R
′
)ONC(R)OCH2CMe2
}
2] [R/R′ ) Me/Me, 1; Me/Et, 2; Me/CH2Ph, 3; Me/Ph, 4; Me/N(C5H10), 5; Et/
84% yields after column chromatography. Compounds
1H
NMR spectroscopies,
−
1−
and X-ray diffraction (for 1, 2, 5, and 9). With the exception of benzonitrile complexes, 1,3-DCA of oxazoline
N-oxides to the PtII-ligated nitriles occurred diastereoselectively and afforded mixtures of enantiomers. Depending
on the substituents on nitriles, asymmetric atoms in both of the formed heterocyclic ligands have the same (SS/
RR) or different (SR/RS) configurations. The heterocyclic ligands were liberated from 1
with excess ethane-1,2-diamine (en) in CH2Cl2 for 1 day at 20 25 C (for R′ ) Me, Et, CH2Ph) and at 50
′ ) Ph) to achieve the free organic species and the well-known [Pt(en)2](Cl)2; the products were separated, and
2,3a-disubstituted 5,6-dihydro-3aH-[1,3]oxazolo[3,2-b][1,2,4]oxadiazoles (11
18) were characterized by ESI+-MS
and 1H and 13C 1H
NMR spectroscopies.
−4 and 6−9 by treatment
−
°
°
C (for
R
−
{
}
Introduction
Among various methods for the activation of nitriles, their
coordination to a metal center has become a widespread
synthetic technique and it allows the performance of such
reactions that are uncommon or even not feasible for the
corresponding noncoordinated species.2 In this context, the
activation of nitriles toward nucleophilic attack received
much attention3,4 and various metal centers proved to be
useful for this kind of transformation. However, the transi-
tion-metal-mediated activation of the CtN bond toward CA
has been paid incomparably less attention from the stand-
In contrast to the wide utility of nitriles as synthons in
organic synthesis, their use in cycloaddition (CA) chemistry
is rather limited. Nitriles are involved in some Diels-Alder
processes or react with dipoles in 1,3-dipolar cycloadditions
(1,3-DCAs) but at elevated temperatures, unless reactions
are intramolecular1 or a nitrile bears a strong electron-
withdrawing group.1 The development of new methods for
accelerating the CA to nitriles and the performance of these
reactions under mild conditions is an important area of
chemical research.
(2) (a) Pombeiro, A. J. L.; Kukushkin, V. Yu. Reactions of coordinated
ligands: General introduction. ComprehensiVe Coordination Chem-
istry, 2nd ed.; Elsevier: New York, 2004; Vol. 1, Chapter 1.29, pp
585-594. (b) Davies, J. A.; Hockensmith, C. M.; Kukushkin, V. Yu.;
Kukushkin, Yu. N. Synthetic Coordination Chemistry: Principles and
Practice; World Scientific: Singapore, 1996; p 492. (c) Constable,
E. C. Metals and Ligand ReactiVity. An Introduction to the Organic
Chemistry of Metal Complexes; VCH: Weinheim, Germany, 1995.
* To whom correspondence should be addressed. E-mail: kukushkin@
vk2100.spb.edu.
‡ St. Petersburg State University.
† University of Joensuu.
(1) Kuznetsov, M. L. Usp. Khim. (Russ. Chem. ReV.) 2002, 71, 307.
10.1021/ic701133b CCC: $37.00
Published on Web 08/29/2007
© 2007 American Chemical Society
Inorganic Chemistry, Vol. 46, No. 20, 2007 8323

Makarycheva-Mikhailova et al.
points of synthetic coordination and organic chemistry,
although the first reviews on the subject have been pub-
lished.5,6
The latter, a rather uncommon mode of nitrile activation
in 1,3-DCAs, was investigated mostly for azides by Purcell
et al.,7 Hay and McLaren,8 and recently by Sharpless et al.9
and also, by some of us, for metal-mediated reactions of RCN
with nitrones10-13 and nitrile oxides.14 Our experimental10,14
and theoretical15,16 results demonstrate that the coordination
of RCN to Pt centers dramatically enhances the reactivity
of the nitriles toward dipoles of both allyl- and propargyl/
allenyl anion types in comparison with CA to uncomplexed
RCN species. In particular, nitriles coordinated to a PtIV
center undergo CA with aromatic and aliphatic nitrones under
very mild conditions.10 The nitriles in the corresponding PtII
complexes exhibit a slightly lower reactivity,11 while at PdII
centers the CA demonstrates lower selectivity12 owing to the
ability of PdII to coordinate O atoms of dipoles along with
coordination of the dipolarophile RCN. All of these indicate
that the Lewis acidity and hard/soft properties of the metal
play important roles in the reaction control.6
Figure 1.
the CA and found that the coordination of RCN to a Pt center
ought to provide even a higher activation effect upon CA in
comparison with the introduction of such a powerful electron-
acceptor group R as CF3.15,16 Furthermore, the calculations
show that the reactivity of oxazoline N-oxides (IUPAC:17
4,5-dihydrooxazole-3-oxides A; Figure 1) toward metal-
mediated 1,3-DCA to RCN is expected to be higher in
comparison with the previously investigated acyclic nitrones
(B1 and B2). It is worthwhile mentioning that oxazoline
N-oxides have efficiently been employed for 1,3-DCAs to
diverse CdC double and CtC triple bonds (including those
functionalized with the nitrile group, which remains intact
after the CA), giving a significant number of ring systems
with useful properties.18,19 In contrast, the reaction of
oxazoline N-oxides with the nitrile CtN moiety has never
been observed in the past. This is probably because of, on
the one hand, the low reactivity of the nitrile group toward
dipoles2,6 and, on the other hand, the substantial instability
of the known oxazoline N-oxides.19-21
Bearing in mind the theoretical results outlined in the
previous paragraph, we were not surprised to find that ligated
nitriles attached to a PtII center are highly competent partners
for CA reactions with oxazoline N-oxides, and all of these
results are described in the Article. To our knowledge, this
report covers the first example of the direct synthesis of a
novel type heterocycle, viz., IUPAC:17 2,3a-disubstituted 5,6-
dihydro-3aH-[1,3]oxazolo[3,2-b][1,2,4]oxadiazoles; gener-
ated by an intermolecular PtII-mediated 1,3-DCA between
an oxazoline N-oxide and coordinated nitrile.
Being interested in amplification of the Pt-mediated 1,3-
DCA reactions to other dipoles, we launched a project aimed
to verify, by theoretical methods, various factors affecting
(3) (a) Kukushkin, V. Yu.; Pombeiro, A. J. L. Chem. ReV. 2002, 102,
1771. (b) Pombeiro, A. J. L.; Kukushkin, V. Yu. Reactions of
Coordinated Nitriles. ComprehensiVe Coordination Chemistry, 2nd ed.;
Elsevier: New York, 2004; Chapter 1.34, Vol. 1, pp 639-660. (c)
Kukushkin, V. Yu.; Pombeiro, A. J. L. Inorg. Chim. Acta 2005, 358,
1. (d) Bokach, N. A.; Kukushkin, V. Yu. Usp. Khim. (Russ. Chem.
ReV.) 2005, 74, 164.
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147, 299. (b) Eglin, J. Comments Inorg. Chem. 2002, 23, 23. (c)
Murahashi, S. I.; Takaya, H. Acc. Chem. Res. 2000, 33, 225. (d)
Kukushkin, Yu. N. Russ. J. Coord. Chem. 1998, 24, 173. (e) Parkins,
A. W. Platinum Met. ReV. 1996, 40, 169. (f) da Rocha, Z. N.;
Chiericato, G., Jr.; Tfouni, E. AdV. Chem. Ser. 1997, 297. (g) Corain,
B.; Basato, M.; Veronese, A. C. J. Mol. Catal. 1993, 81, 133. (h)
Chin, J. Acc. Chem. Res. 1991, 24, 145.
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59, 823.
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(7) (a) Ellis, W. R.; Purcell, W. L. Inorg. Chem. 1982, 21, 834. (b) Hall,
J. H.; De La Vega, R. L.; Purcell, W. L. Inorg. Chim. Acta 1985,
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Chem. Soc. 2003, 125, 9983. (b) Himo, F.; Demko, Z. P.; Noodleman,
L.; Sharpless, K. B. J. Am. Chem. Soc. 2002, 124, 12210. (c) Demko,
Z. P.; Sharpless, K. B. Org. Lett. 2001, 3, 4091. (d) Demko, Z. P.;
Sharpless, K. B. J. Org. Chem. 2001, 66, 7945.
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L.; Kukushkin, V. Yu. Inorg. Chem. 2001, 40, 264.
Experimental Section
Instrumentation and Materials. C, H, and N elemental analyses
were carried out by the Department of Organic Chemistry of the
St.Petersburg State University. Positive-ion electrospray ionization
time-of-flight (ESI-TOF) mass spectra of 11-18 were obtained on
a MX-5310 mass spectrometer, using 1:1 (v/v) H2O/CH3CN as the
solvent stream; the probe concentration was ca. 10-5 M. Spectra
were recorded in a m/z range comprised between 10 and 3000 Da:
flow rate 10 µL/min, spray tip potential 3.3 kV, nozzle potential
50.00 V, skimmer voltage 18.00 V, nozzle temperature 40 °C.
Positive-ion fast atom bombardment (FAB) mass spectra of the PtII
(12) Bokach, N. A.; Krokhin, A. V.; Nazarov, A. A.; Kukushkin, V. Yu.;
Haukka, M.; Frau´sto da Silva, J. J. R.; Pombeiro, A. J. L. Eur. J.
Inorg. Chem. 2005, 3042.
(13) Charmier, M. A. J.; Kukushkin, V. Yu.; Pombeiro, A. J. L. Dalton
Trans. 2003, 2540.
(14) (a) Bokach, N. A.; Khripoun, A. V.; Kukushkin, V. Yu.; Haukka, M.;
Pombeiro, A. J. L. Inorg. Chem. 2003, 42, 896. (b) Bokach, N. A.;
Kukushkin, V. Y.; Haukka, M.; Pombeiro, A. J. L. Eur. J. Inorg. Chem.
2005, 845.
(15) Kuznetsov, M. L.; Kukushkin, V. Yu. J. Org. Chem. 2006, 71, 582.
(16) (a) Kuznetsov, M. L.; Nazarov, A. A.; Kozlova, L. V.; Kukushkin,
V. Yu. J. Org. Chem. 2007, 72, 4475. (b) Kuznetsov, M. L.;
Kukushkin, V. Yu.; Dement’ev, A. I.; Pombeiro, A. J. L. J. Phys.
Chem. A 2003, 107, 6108. (c) Kuznetsov, M. L.; Kukushkin, V. Yu.;
Haukka, M.; Pombeiro, A. J. L. Inorg. Chim. Acta (Special Volume
dedicated to J. J. R. Frau´sto da SilVa) 2003, 356, 85.
(17) http://www.iupac.org/nomenclature/index.html.
(18) For a review, see: Dirat, O.; Kouklovsky, C.; Mauduit, M.; Langlois,
Y. Pure Appl. Chem. 2000, 72, 1721.
(19) (a) Amado, A. F.; Kouklovsky, C.; Langlois, Y. Synlett 2005, 1, 103.
(b) Voituriez, A.; Moulinas, J.; Kouklovsky, C.; Langlois, Y. Synthesis
2003, 9, 1419. (c) Collon, S.; Kouklovsky, C.; Langlois, Y. Eur. J.
Org. Chem. 2002, 21, 3566. (d) Dirat, O.; Kouklovsky, C.; Mauduit,
M.; Langlois, Y. Pure Appl. Chem. 2000, 72, 1721. (e) Mauduit, M.;
Kouklovsky, C.; Langlois, Y. Eur. J. Org. Chem. 2000, 8, 1595. (f)
Mauduit, M.; Kouklovsky, C.; Langlois, Y.; Riche, C. Org. Lett. 2000,
2, 1053.
(20) Ashburn, S. P.; Coates, R. M. J. Org. Chem. 1985, 50, 3076.
(21) Ashburn, S. P.; Coates, R. M. J. Org. Chem. 1984, 49, 3127.
8324 Inorganic Chemistry, Vol. 46, No. 20, 2007

Cycloaddition of Oxazoline N-Oxides to Nitriles
metrically and were also constrained to ride on their parent atoms
with C-H ) 0.95-0.99 Å and Uiso ) 1.2-1.5Uiso (parent atom).
The crystallographic details for 1, 2, 5, and 9 are summarized in
Table 1 and the selected bond lengths and angles in Table 2.
PtII-Mediated 1,3-DCA (a General Procedure). (i) In Situ
Synthesis of Oxazoline N-Oxides. A suspension of 2-(hydroxyl-
amino)-2-methyl-1-propanol (50 mg, 0.36 mmol) in dichlo-
romethane (1 mL) was added to triethyl orthoacetate (70 mg, 0.45
mmol) for C or triethyl orthopropionate (80 mg, 0.45 mmol) for
D, and the reaction mixture was stirred at room temperature for 1
h, whereupon triethylamine (0.05 mL, 0.36 mmol) was added and
the solution was stirred at room temperature for 15 min.
Figure 2. Oxazoline N-oxides employed for the 1,3-DCAs: R ) Me (C);
Et (D).
complexes were obtained on a MS-50C (Kratos) instrument by
bombarding 3-nitrobenzyl alcohol matrices of the samples with 8
keV (ca. 1.28 × 1015 J) Xe atoms. Thin-layer chromatography
(TLC) was performed on Merck on 60 F254 SiO2 plates. IR spectra
(4000-400 cm-1) were recorded on a Shimadzu FTIR-8400S
instrument in KBr pellets. 1H and 13C{1H} NMR spectra were
measured in CDCl3 on a Bruker AMX-300 spectrometer at ambient
temperature.
Solvents were obtained from commercial sources and used as
received. In the series [PtCl2(R′CN)2] [R′ ) Me, Et, CH2Ph, Ph,
N(CH2)5], the former complex was obtained as a mixture of the
cis- and trans-[PtCl2(MeCN)2] isomers in a ratio of ca. 5:1 by the
known method,22 while the other compounds were prepared as pure
trans isomers in accordance with the published procedures.23
Oxazoline N-oxides (C and D; Figure 2) were synthesized from
RC(OEt)3 (R ) Me and Et, respectively) and 2-(hydroxylamino)-
2-methyl-1-propanol by the literature method.20,21
X-ray Crystal Structure Determinations. The crystals of 1, 2,
5, and 9 were obtained by slow evaporation of the solvent from a
CHCl3 or CDCl3 solution of the corresponding complexes. The
crystals were immersed in cryo-oil, mounted in a nylon loop, and
measured at a temperature of 105-150 K. The X-ray diffraction
data were collected by means of a Nonius Kappa CCD diffracto-
meter using Mo KR radiation (λ ) 0.710 73 Å). The Denzo-
Scalepack24 or EValCCD25 program packages were used for cell
refinements and data reductions. The structures were solved by
direct methods using SHELXS-97,26 SIR-97,27a or SIR-200427b with
the WinGX28 graphical user interface. An empirical absorption
correction was applied to all of the data (XPREP in SHELXTL,
version 6.14-1,29 or SADABS, version 2.1030). Structural refinements
were carried out using SHELXL-97.31 The D atom of CDCl3 in 9
was refined isotropically. Other H atoms were positioned geo-
(ii) CA Reactions. This solution was added to a suspension of
trans-[PtCl2(R′CN)2] [0.12 mmol; R′ ) Me, Et, CH2Ph, Ph;
N(C5H10)] in CH2Cl2 (2 mL). The reaction mixture was stirred at
room temperature for 24 h to give a pale-yellow solution,
whereupon the solvent was evaporated at room temperature. The
pale-yellow oily residue formed was dissolved in CH2Cl2 (1 mL)
and purified by column chromatography (see later). Evaporation
of the solvent gave the pale-yellow crystalline residue. Yield: 65-
70%. Below we provide characterizations of the complexes
[PtCl2L2], where L is depicted in Figure 3.
1
cis/trans-1 (cis/trans Isomers in a Ratio of 2:1 Based on H
NMR Integration). Anal. Calcd for C16H28N4Cl2O4Pt: C, 31.69;
H, 4.65; N, 9.24. Found: C, 31.29; H, 4.51; N, 8.92. TLC: Rf )
0.37 [eluent: 1:10 (v/v) Me2CO/CHCl3]. FAB+-MS: m/z 629 [M
+ Na]+. IR spectrum (KBr, selected bands, cm-1): 1658 ν(CdN).
1H NMR [δ (ppm), J (Hz)]: 1.09 (trans), 1.25 (cis), 1.27 (trans),
and 1.32 (cis) (four s, 6H, CH3C6), 2.04 (trans) and 2.21 (cis) (two
s, 3H, CH3C2), 2.67 (cis) and 2.69 (trans) (two s, 3H, CH3C3a),
3.12 and 3.67 (cis, two d, J ) 8.4), 3.51 and 3.74 (trans, two d, J
) 9.3, 2H, C5H2). In the cis/trans isomeric mixture, attribution of
signals is based on the spectra of the individual trans isomer
obtained in the reaction between trans-1 and nitrone C. For trans-
1
1. H NMR [δ (ppm), J (Hz)]: 1.09, 1.27, (two s, 6H, CH3C6),
2.04 (s, 3H, CH3C2), 2.69 (s, 3H, CH3C3a), 3.51 and 3.74 (two d,
J ) 9.3, 2H, C5H2). 13C NMR [δ (ppm)]: 13.6 (CH3C2), 18.6, 19.7,
23.2, 24.8, and 27.7 (CH3C6 and CH3C3a), 68.3 (C6), 72.3 and 72.9
(C5); the resonances from C2 and C3a were not observed. Yield:
46% (33.5 mg).
2. Anal. Calcd for C18H32N4Cl2O4Pt: C, 34.07; H, 5.08; N, 8.83.
Found: C, 34.26; H, 5.08, N, 8.85. TLC: Rf ) 0.58 [eluent: 1:10
(v/v) Me2CO/CHCl3]. FAB+-MS: m/z 562 [M - 2HCl]+, 633 [M
- H]+, 657 [M + Na]+. IR spectrum (KBr, selected bands, cm-1):
1657 ν(CdN). 1H NMR [δ (ppm), J (Hz)]: 1.26 and 1.28 (two s,
6H, CH3C6), 1.44 (t, J ) 7.3, 3H, CH3CH2C2), 2.05 (s, 3H, CH3C3a),
3.08-3.15 and 3.28-3.33 (two m, 2H, CH2C2), 3.30 and 3.74 (two
d, J ) 9.2, 2H, C5H2). 13C NMR [δ (ppm)]: 10.1 (CH3CH2C2),
20.0, 22.2, and 26.3 (CH3C6, CH3C3a, and CH2C2), 69.2 (C6), 73.2
(C5), 119.9 (C3a), 176.5 (C2). Yield: 70% (53.3 mg).
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3. Anal. Calcd for C28H36N4Cl2O4Pt: C, 44.33; H, 4.78; N, 7.39.
Found: C, 44.43; H, 4.91; N, 7.22. TLC: Rf ) 0.58 [eluent: 1:10
(v/v) Me2CO/CHCl3]. FAB+-MS: m/z 711 [M - 2Cl + Na]+, 735
[M - 2Cl + 2Na]+. IR spectrum (KBr, selected bands, cm-1): 1644
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M. J. Appl. Crystallogr. 2003, 36, 220.
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Systems: Bruker AXS Inc.: Madison, WI, 2005.
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1
ν(CdN). H NMR [δ (ppm), J (Hz)]: 0.95 and 1.19 (two s, 6H,
CH3C6), 2.11 (s, 3H, CH3C3a), 3.43 and 3.69 (two d, J ) 9.2, 2H,
C5H2), 4.26 and 4.85 (two d, J ) 15.3, 2H, CH2C2), 7.36 and 7.48
(two m, 5H, PhCH2C2). 13C NMR [δ (ppm)]: 19.6, 25.6, and 26.3
(CH3C3a and CH3C6), 34.4 (CH2PhC2), 62.4 (C6), 72.7 (C5), 116.7
(C3a), 127.8, 128.6, 129.2, and 132.3 (C-Ph), 170.9 (C2). Yield:
84% (76.5 mg).
4. Anal. Calcd for C26H32N4Cl2O4Pt: C, 42.75; H, 4.42; N, 7.67.
Found: C, 42.58; H, 4.48; N, 7.58. TLC: Rf ) 0.63 [eluent: 1:10
Inorganic Chemistry, Vol. 46, No. 20, 2007 8325

Makarycheva-Mikhailova et al.
Table 1. Crystallographic Data for 1, 2, 5, and 9
1
2
5
9‚2CDCl3
empirical formula
fw
temp (K)
λ (Å)
cryst syst
space group
a (Å)
b (Å)
c (Å)
R (deg)
â (deg)
γ (deg)
V (Å3)
C16H28Cl2N4O4Pt
C18H32Cl2N4O4Pt
634.47
150(2)
0.710 73
monoclnic
C2/c
20.5932(6)
9.1472(4)
14.4093(4)
90
117.766(3)
90
2401.75(16)
4
1.755
6.094
C28H36Cl2N4O4Pt
758.60
105(2)
0.710 73
monoclinic
P21/n
9.4537(7)
10.5337(5)
15.6088(11)
90
105.088(6)
90
1500.78(17)
2
1.679
4.892
C26H42D2Cl8N6O4Pt
985.37
120(2)
0.710 73
triclinic
P1h
9.1351(9)
9.9820(4)
10.0486(6)
81.645(5)
88.340(6)
86.454(6)
904.65(11)
1
1.809
4.510
18 943
4132
0.0210
0.0131
0.0301
606.41
120(2)
0.710 73
monoclinic
C2/c
20.1567(5)
9.6656(2)
12.1219(2)
90
116.455(2)
90
2114.36(9)
4
Z
F
calc (Mg/m3)
1.905
6.918
λ(Mo Ka) (mm-1
)
no. of reflns
11 503
2421
0.0521
0.0188
0.0456
10 359
2354
0.0692
0.0415
8440
2948
0.0343
0.0217
no. of unique reflns
Rint
R1a (I g 2σ)
wR2b (I g 2 σ)
0.0949
0.0381
a R1 ) ∑||Fo| - |Fc||/∑|Fo|. b wR2 ) [∑[w(Fo - Fc )2]/∑[w(Fo )2]]1/2
.
2
2
2
28.4, and 48.8 (CH2), 67.6 (C6), 73.6 (C5), 119.8 (C3a), 157.7 (C2).
Yield: 61% (54.5 mg).
Table 2. Selected Bond Lengths (Å) and Angles (deg) for 1, 2, 5, and
9
1
cis/trans-6 (cis/trans Isomers in a Ratio of 1:2 Based on H
1
2
5
9
NMR Integration). Anal. Calcd for C18H32N4Cl2O4Pt: C, 34.07;
H, 5.08; N, 8.83. Found: C, 34.10; H, 5.19; N, 8.67. TLC: Rf )
0.49 [eluent: 1:5 (v/v) Me2CO/CHCl3]. FAB+-MS: m/z 658 [M
- 2HCl]+, 695 [M - HCl]+. IR spectrum (KBr, selected bands,
Pt1-N1
Pt1-Cl1
N1-C6
N1-C1
O1-N2
N2-C2
C6-O2
2.036(2)
2.2951(6)
1.472(3)
1.278(3)
1.480(3)
1.509(4)
1.419(3)
2.012(5)
2.305(2)
1.483(8)
1.272(9)
1.475(8)
1.502(9)
1.409(8)
2.0164(12)
2.3057(4)
1.4632(19)
1.299(2)
1.4622(16)
1.508(2)
2.011(2)
2.2930(9)
1.478(4)
1.277(4)
1.468(4)
1.503(4)
1.395(4)
1
cm-1): 1658 ν(CdN). H NMR [δ (ppm), J (Hz)]: 1.11 (trans)
and 1.12 (cis) (two t, J ) 8.0, 3H, CH3CH2C3a), 1.24, 1.26, 1.29,
and 1.32 (four s, 6H, CH3C6), 2.00, 2.20, 2.54, and 2.78 (four m,
2H, CH2C3a), 2.54 (cis) and 2.69 (trans) (two s, 3H, CH3C2), 3.08
and 3.63 (two d, J ) 8.7, cis), 3.51 and 3.74 (two d, J ) 9.2, trans,
2H, H2C5). 13C NMR [δ (ppm)]: 8.8 and 9.2 (CH3CH2C3a), 14.3,
14.5, 20.3, 20.9, 25.3, and 25.8 (CH3C2 and CH3C6), 32.7 and 33.2
(CH2C3a), 68.1 and 68.5 (C6), 73.0 and 73.8 (C5), 122.3 and 122.8
(C3a), 170.0 and 170.5 (C2). Yield: 70% (53.3 mg). In the cis/
trans isomeric mixture, attribution of signals is based on the spectra
of the pure trans isomer obtained in the reaction between trans-
[PtCl2(EtCN)2] and nitrone D. Trans isomer. 1H NMR [δ (ppm), J
(Hz)]: 1.17 (t, J 8.0, 3H, CH3CH2C3a), 1.24 and 1.25 (two s, 6H,
CH3C6), 2.21 and 2.49 (four m, 2H, CH2C3a), 2.72 (s, 3H, CH3C2),
3.70 (m, 2H, H2C5). 13C NMR [δ (ppm)]: 8.8 (CH3CH2C3a), 14.2,
20.2, 20.9, and 26.8 (CH3C2 and CH3C6), 31.6 (CH2C3a), 68.5 (C6),
73.8 (C5), 122.5 (C3a); C2 was not detected.
1.4065(19)
Cl1-Pt1-N1
N1-C6-O2
O1-N2-C2
87.94(6)
110.4(2)
107.1(2)
88.60(16)
111.8(5)
108.4(5)
89.58(4)
106.64(12)
109.13(11)
87.61(7)
111.3(3)
109.3(3)
(v/v) Me2CO/CHCl3]. FAB+-MS: m/z 634 [M - H]+. IR spectrum
(KBr, selected bands, cm-1): 1656 ν(CdN). 1H NMR [δ (ppm), J
(Hz)]: (a mixture of diastereomers in a ratio of 1:1): 1.33, 1.34,
1.36, and 1.39 (four s, 6H, CH3C6), 2.10, 2.15, 2.19, and 2.30 (four
s, 3H, CH3C3a), 3.71-3.78 (m, 2H, CH2C5), 7.43 (t, J ) 7.7, p-Ph),
7.60 (m, o- and m-Ph), 8.69 (t, J ) 7.7, p-Ph), 9.18 (two d, J )
7.2, o-Ph, 5H, H-Ph). 13C NMR [δ (ppm)]: 19.8, 26.0, 26.1, 26.2,
27.2, and 27.9 (CH3C3a and CH3C6), 69.0 (C6), 73.1, 73.2, and 73.3
(C5), 120.7, 121.0, and 121.1 (C3a), 122.3, 128.3, 128.6, 130.2,
130.5, 130.6, 133.1, and 133.6 (C-Ph), 167.2 (C2). Yield: 75%
(65.7 mg).
7. Anal. Calcd for C20H36N4Cl2O4Pt: C, 36.26; H, 5.48; N, 8.46.
Found: C, 35.06; H, 5.09; N, 8.55. TLC: Rf ) 0.67 [eluent: 1:10
(v/v) Me2CO/CHCl3]. FAB+-MS: m/z 629 [M - Cl]+. IR spectrum
(KBr, selected bands, cm-1): 1658 ν(CdN). 1H NMR [δ (ppm), J
(Hz)]: 1.15 (t, J ) 7.9, 3H, CH3CH2C3a), 1.23 and 1.25 (two s,
6H, CH3C6), 1.47 (t, J ) 9.2, 3H, CH3CH2C2), 2.20 and 2.52 (two
m, 2H, CH2C3a), 3.15 and 3.31 (two m, 2H, CH2C2), 3.50 and 3.71
(two d, J ) 8.7, 2H, H2C5). 13C NMR [δ (ppm)]: 8.3 and 9.7 (CH3-
CH2C2 and CH3CH2C3a), 19.6 and 23.5 (MeC6), 26.3 and 31.1
(CH2C3a, CH2C2), 67.9 (C6), 73.2 (C5), 121.9 (C3), 161.3 (C2).
Yield: 66% (52.5 mg).
5. Anal. Calcd for C24H42N6Cl2O4Pt‚H2O: C, 37.80; H, 5.81;
N, 11.02. Found: C, 38.85; H, 5.78; N, 10.95. TLC: Rf ) 0.64
[eluent: 1:10 (v/v) Me2CO/CHCl3]. FAB+-MS: m/z 671 [M -
Cl]+, 744 [M]+. IR spectrum (KBr, selected bands, cm-1): 1651
1
ν(CdN). H NMR [δ (ppm), J (Hz)]: 1.22 and 1.24 (two s, 6H,
CH3C6), 1.58-1.93 (m, 6H, CH2), 1.99 (s, 3H, CH3C3a), 3.61 and
4.00 (two d and d, J ) 8.7, 2H, H2C5), 4.15-4.70 (m, 4H, NCH2).
13C NMR [δ (ppm)]: 20.3, 24.3, and 25.9 (CH3C3a, MeC6), 27.4,
8. Anal. Calcd for C30H40N4Cl2O4Pt: C, 45.80; H, 5.13; N, 7.12.
Found: C, 45.87; H, 5.17; N, 7.02. TLC: Rf ) 0.67 [eluent: 1:10
(v/v) Me2CO/CHCl3]. FAB+-MS: m/z 784 [M - H]+, 808 [M +
Na]+. IR spectrum (KBr, selected bands, cm-1): 1651 ν(CdN).
1H NMR [δ (ppm), J (Hz)]: 0.93 and 1.18 (two s, 6H, CH3C6),
1.16 (t, J ) 7.8, 3H, CH3CH2C3a), 2.29 and 2.59 (two m, br, 2H,
Figure 3. 2,3a-Disubstituted 5,6-dihydro-3aH-[1,3]oxazolo[3,2-b][1,2,4]-
oxadiazoles (L) with an atom numbering scheme.
8326 Inorganic Chemistry, Vol. 46, No. 20, 2007

Cycloaddition of Oxazoline N-Oxides to Nitriles
CH2C3a), 3.63 and 3.68 (two d, J ) 9.2, 2H, C5H2), 4.33 and 4.89
(two d, J ) 15.3, 2H, CH2C2), 7.32 and 7.57 (two m, 5H, H-Ph).
13C NMR [δ (ppm)]: 8.4 (CH3CH2C3a), 19.2 and 26.4 (CH3C6),
31.3 and 34.7 (CH2C3a, CH2C2), 68.2 (C6), 73.5 (C5), 122.3 (C3a),
127.8, 128.8, 129.5, and 132.0 (C-Ph), 168.7 (C2). Yield: 79%
(74.6 mg).
9. Anal. Calcd for C28H36N4Cl2O4Pt: C, 44.33; H, 4.78; N, 7.39.
Found: C, 44.10; H, 4.80; N, 7.29. TLC: Rf ) 0.59 and 0.64
[eluent: 1:10 (v/v) Me2CO/CHCl3]. FAB+-MS: m/z 686 [M -
2HCl]+, 759 [M]+. IR spectrum (KBr, selected bands, cm-1): 1631
ν(CdN). 1H NMR [δ (ppm), J (Hz)]: (a mixture of diastereomers
in a 1:1 ratio) 1.02 (t, J ) 8.0) and 1.15 (t, J ) 8.1) (3H, CH3-
CH2C3a), 1.31, 1.33, 1.36, and 1.38 (four s, 3H, CH3C6), 2.13, 2.30,
2.62, and 2.77 (four m, 2H, CH2C3a), 3.68-4.08 (two d and m, J
) 9.5 and 8.7, 2H, H2C5), 7.44 (m, p-Ph), 7.60 (m, o- and m-Ph),
8.69 (m, p-Ph), 9.25 (m, o-Ph, 5H, H-Ph). 13C NMR [δ (ppm)]:
8.6 (CH3CH2C3a), 20.0, 26.8, and 27.0 (CH3C6), 31.1, 31.2, and
31.7 (CH2C3a), 67.7 and 68.0 (C6), 74.1 and 74.2 (C5), 122.5 and
122.8 (C3a), 123.7, 123.8, and 124.0 (Cipso), 128.4, 128.6, 128.7,
130.3, 130.5, 130.7, 130.9, 133.1, and 133.8 (C-Ph), 166.0 (C2).
Yield: 77% (70.1 mg).
10. Anal. Calcd for C26H46N6Cl2O4Pt: C, 40.42; H, 6.00; N,
10.88. Found: C, 40.20; H, 5.90; N, 10.79. TLC: Rf ) 0.63 [eluent:
1:5 (v/v) Me2CO/CHCl3]. FAB+-MS: m/z 773 [M]+. IR spectrum
(KBr, selected bands, cm-1): 1655 ν(CdN). 1H NMR [δ (ppm), J
(Hz)]: 0.96 and 0.98 (two t, J ) 6.54, 3H, CH3CH2C3a), 1.22 and
1.26 (two s, 6H, CH3C6), 1.69 and 1.85 (two m, br, 6H, CH2), 1.99
and 2.59 (two m, 2H, CH2C3a), 3.68 and 4.25 (d and two d, J )
8.7, 2H, H2C5), 4.30-4.70 (m, 4H, NCH2). 13C NMR [δ (ppm)]:
9.2 (CH3CH2C3a), 20.4, 24.4, and 25.9 (CH3C3a, MeC6), 28.1, 32.1,
and 48.9 (CH2), 67.6 (C6), 74.2 (C5), 122.1 (C3a), 158.5 (C2).
Yield: 42% (38.9 mg).
Liberation of 3a-R′-2-R-5,6-dihydro-3aH-[1,3]oxazolo[3,2-b]-
[1,2,4]oxadiazoles from Complexes 1-4 and 6-9. An excess of
neat ethane-1,2-diamine (en; 60 mg, 2.0 mmol) was added to a
solution of the corresponding [PtCl2L2] complex (0.05 mmol) in
dichloromethane (2 mL), and the reaction mixture was stirred for
1 day at 20-25 °C (R′ ) Me, Et, CH2Ph) and 1 day at 50 °C in
MeCN (R′ ) Ph). In the cases of R′ ) Me, Et, and CH2Ph, during
this time, the initially pale-yellow solution turned practically
colorless and the colorless precipitate of the known32 [Pt(en)2](Cl)2
complex was formed. The addition of water (0.5 mL) to the reaction
mixture results in dissolution of the solid and gives a pale-yellow
aqueous phase along with a colorless organic layer; the latter was
separated, washed with water, and dried with Na2SO4. In the case
of R′ ) Ph, the solvent was evaporated at room temperature and
an oily residue formed was partially dissolved upon the addition
of CH2Cl2 followed by the addition water to give two layers. The
dichloromethane layer was separated and dried with Na2SO4. In
all cases, evaporation of the solvent afforded heterocycles 11-18
as colorless oily residues in almost quantitative yields. The
heterocycles from complexes 5 and 10 were not liberated even for
1 week at 35 °C.
(two d, J ) 8.7, 2H, C5). 13C NMR [δ (ppm)]: 10.9 (CH3CH2C2),
19.3 (CH2C2), 20.1, 25.4, and 26.5 (CH3C3a, CH3C6), 69.2 (C6),
73.2 (C5), 121.2 (C3a), 168.3 (C2). Yield: 73% (13.4 mg).
13. ESI+-MS: m/z 247 [M + H]+. 1H NMR [δ (ppm), J (Hz)]:
1.09 and 1.20 (two s, 6H, CH3C6), 1.77 (s, 3H, CH2C3a), 3.03 and
3.59 (two d, J ) 8.4, 2H, H2C5), 3.61 and 3.71 (two d, J ) 14.8,
2H, CH2C2), 7.32 (m, 5H, CH2Ph). 13C NMR [δ (ppm)]: 20.0 and
25.6 (MeC6), 26.8 (CH2C3a), 32.8 (CH2C2), 67.4 (C6), 72.2 (C5),
1241.4 (C3a), 127.3, 128.7, and 128.8 (C-Ph), 134.2 (Cipso), 165.4
(C2). Yield: 86% (22.4 mg).
14. ESI+-MS: m/z 233 [M + H]+. 1H NMR [δ (ppm), J (Hz)]:
1.34, 1.39 (two s, 6H, CH3C6), 1.89 (s, 3H, CH3C3a), 3.31 and 3.74
(two d, J ) 9.3, 2H, H2C5), 7.46 (m, 2H, m-Ph), 7.56 (m, 1H,
p-Ph), 7.95 (d, J ) 7.2, 2H, o-Ph). 13C NMR [δ (ppm)]: 20.4 and
25.7 (MeC6), 26.8 (CH3C2), 67.6 (C6), 72.3 (C5), 124.6 (C3a), 128.5
(o- and m-Ph), 132.3 (p-Ph), 162.4 (C2). Yield: 15% (3.5 mg).
15. ESI+-MS: m/z 185 [M + H]+. 1H NMR [δ (ppm), J (Hz)]:
1.01 (t, 3H, J ) 7.3, CH3CH2C3a), 1.22 and 1.27 (two s, 6H,
CH3C6), 1.85 and 2.07 (two m, 2H, CH2C3a), 2.05 (s, 3H, CH3C2),
3.23 and 3.66 (two d, J ) 8.9, 2H, H2C5). 13C NMR [δ (ppm)]:
8.4 (CH3CH2C3a), 11.5 (CH3C2), 20.4 and 25.7 (CH3C6), 32.3
(CH2C3a), 66.9 (C6), 71.9 (C5), 124.0 (C3a), 163.7 (C2). Yield: 80%
(14.6 mg).
16. ESI+-MS: m/z 221 [M + Na]+. 1H NMR [δ (ppm), J (Hz)]:
1.02 (t, 3H, J ) 7.7, CH3CH2C3a), 1.23, 1.25, and 1.28 (t and two
s, 9H, CH3CH2C2 and CH3C6), 1.86 and 2.12 (two m, 2H, CH2C3a),
2.38 (q, J ) 7.7, 2H, CH2C2), 3.23 and 3.66 (two d, J ) 8.7, 2H,
H2C5). 13C NMR [δ (ppm)]: 8.9 (CH3CH2C3a), 11.7 (CH3CH2C2),
19.9 (CH2C2), 20.7 and 26.2 (MeC6), 32.7 (CH2C3a), 67.3 (C6), 72.2
(C5), 124.4 (C3a), 168.4 (C2). Yield: 84% (16.7 mg).
17. ESI+-MS: m/z 261 [M + H]+. 1H NMR [δ (ppm), J (Hz)]:
1.01 (t, 3H, J ) 7.8, CH3CH2C3a), 1.08 and 1.18 (two s, 6H,
CH3C6), 1.87 and 2.11 (two m, 2H, CH2C3a), 3.06 and 3.59 (two
d, J ) 8.8, 2H, H2C5), 3.64 and 3.73 (two d, J ) 14.8, 2H, CH2C2),
7.33 (m, 5H, CH2Ph). 13C NMR [δ (ppm)]: 8.5 (CH3CH2C3a), 20.0
and 25.8 (MeC6), 32.7 (CH2C3a), 32.9 (CH2C2), 67.1 (C6), 72.0 (C5),
124.1 (C3a), 127.3, 128.7, and 128.8 (C-Ph), 134.3 (Cipso), 165.5
(C2). Yield: 85% (22.1 mg).
18. ESI+-MS: m/z 247 [M + H]+. 1H NMR [δ (ppm), J (Hz)]:
1.08 (t, 3H, J ) 7.4, CH3CH2C3a), 1.31, 1.38 (two s, 6H, and
CH3C6), 1.98 and 2.23 (two m, 2H, CH2C3a), 3.30 and 3.73 (two
d, J ) 9.2, 2H, H2C5), 7.46 (m, 2H, m-Ph), 7.55 (m, 1H, p-Ph),
7.96 (d, J ) 7.4, 2H, o-Ph). 13C NMR [δ (ppm)]: 8.5 (CH3CH2C3a),
20.4 and 25.9 (MeC6), and 32.5 (CH2C3a), 67.3 (C6), 72.1 (C5),
124.6 (C3a), 128.5 (o- and m-Ph), 132.2 (p-Ph), 162.5 (C2). Yield:
33% (8.1 mg).
Results and Discussion
We have previously demonstrated that PtIV centers activate
nitrile substrates toward 1,3-DCA of nitrile oxides in a
significantly more effective way than PtII centers; the latter
have almost no effect on this reaction.33 In the current work,
we found that the activation of RCN by PtIV centers toward
1,3-DCA is so significant that the reaction loses its selectivity
and the formation of a broad of mixture of products was
observed. Unlikely, a PtII center provides a sufficient
activation to perform the reaction and to make it selective.
Metal-Mediated 1,3-DCA of Oxazoline N-Oxides to
(Nitrile)platinum(II) Complexes. The oxazoline N-oxides
C and D were obtained in situ by a known method,20,21 which
includes the reaction between HOCH2C(Me)2NHOH‚HCl
11. ESI+-MS: m/z 171 [M + H]+. 1H NMR [δ (ppm), J (Hz)]:
1.29 and 1.34 (two s, 6H, CH3C6), 2.22 (s, 3H, CH3C2), 2.68 (s,
3H, CH3C3a), 3.13 and 3.69 (two d, J ) 8.3, 2H, H2C5). 13C NMR
[δ (ppm)]: 11.5 (CH3C2), 20.3 and 25.5 (CH3C6), 26.6 (CH3C3a),
67.2 (C6), 72.0 (C5), 121.3 (C3a), 163.6 (C2). Yield: 55% (9.4 mg).
12. ESI+-MS: m/z 207 [M + Na]+. 1H NMR [δ (ppm), J (Hz)]:
1.26 (t, J ) 7.7, 3H, CH3CH2C2), 1.28 and 1.29 (two s, 6H, CH3C6),
1.77 (s, 3H, CH3C3a), 2.34 (q, J ) 7.7, 2H, CH2C2), 3.22 and 3.67
(32) Jo¨rgensen, S. M. J. Prakt. Chem. 1889, 39, 1.
Inorganic Chemistry, Vol. 46, No. 20, 2007 8327

Makarycheva-Mikhailova et al.
Scheme 1
and RC(OEt)3 (R ) Me, Et) in CH2Cl2 followed by the
addition of NEt3. The solution of C (or D) prepared by this
method was added to a solution [R′ ) Et, CH2Ph, Ph,
N(C5H10)] or suspension (R′ ) Me) of trans/cis-[PtCl2-
(R′CN)2] in CH2Cl2; a molar ratio of the reactants was ca.
3:1. After 18-20 h, the reaction mixture was evaporated in
a flow of N2 to ca. one-fourth of the initial volume and then
the target material was purified by column chromatography
on SiO2. Characterization of the products (see later) revealed
that the reactions of trans/cis-[PtCl2(R′CN)2] with oxazoline
N-oxides C and D afforded the dihydrooxazolo-1,2,4-
oxadiazole complexes PtII (Scheme 1, route I).
NMR data also show that the CA occurred diastereo-
selectively for compounds 1-3, 5-8, and 10. Thus, the 1H
NMR spectra of trans-1-3 and 6-8 display one set of
signals due to an enantiomeric mixture with the same (SS/
RR) configuration of both C3a and C′3a atoms, while for 5
and 10, one of the two HC5 protons gives two signals of
very close chemical shift values (the difference is less than
0.01 ppm). These two resonances belong to two bicyclic
moieties of different (R and S) configuration. In the 13C-
{1H} NMR spectra, peaks from the asymmetric C3a carbons
are also duplicate, and this fact gives an additional argument
that favors the formation of another pair of enantiomers. The
1H and 13C{1H} NMR spectra of 4 and 9 show several sets
of signals probably due to the formation of a diastereomeric
(RR/SS/RS) mixture (see later for a discussion of the
stereochemistry of the CA).
The CA described in this section is PtII-mediated. Indeed,
it was proved in a separate experiment that the most electron-
deficient nitrile of the series, i.e., PhCN, in CDCl3 in the
absence of the metal center does not react with the dipoles
at 50 °C for 20 h and only gradual degradation of the
oxazoline N-oxides was observed under those conditions.
Moreover, the coordination increases the polarization of the
CtN bond, and this make the CA highly regioselective.15,16
X-ray Structure Determinations of (Dihydrooxazolo-
1,2,4-oxadiazole)platinum(II) Complexes. In 1, the bicyclic
ligands lie in the cis position to each other, while compounds
2, 5, and 9 exhibit the trans configuration. The Pt1-N1 bond
lengths in the complexes are typical for (imine)platinum(II)
species; the Pt1-N1 bond length in 1 [2.036(2) Å] is slightly
longer than those [2.011(2)-2.0164(12) Å] in 2, 5, and 9
probably because of a higher ground-state trans influence
of the Cl ligand compared to the imine N. In 1, 2, 5, and 9,
the bond distances N1-C1 [1.272(9)-1.299(2) Å] in the
bicyclic ligands are typical for the NdC double bond,34 while
the N1-C6 bond lengths [1.4632(19)-1.483(8) Å] belong
Complexes 1-10 were isolated as yellow solids and
characterized by elemental analyses (C, H, N), FAB+-MS,
IR, and 1H and 13C{1H} NMR spectroscopies, and X-ray data
(for 1, 2, 5, and 9). Thus, the complexes gave satisfactory
microanalysis and the expected fragmentation/isotopic pattern
in FAB+-MS; the typical ions that were detected are [M]+,
[M + Na]+, and [M - HCl]+. A comparison of the IR spectra
of 1-10 with those of the starting materials shows the
absence of the ν(CtN) stretching vibrations at ca. 2300
cm-1, and the availability of strong ν(CdN) vibrations
emerged in the range between 1630 and 1660 cm-1.
1
For all complexes, signal integration in the H NMR
spectra gives evidence that the reaction between each of the
coordinated nitrile and an oxazoline N-oxide proceeds in a
1:1 ratio. 1H NMR spectra of 1-10 display the characteristic
doublets of the C5 protons in the range between 3.08 and
4.25 ppm. In the 13C{1H} NMR spectra of these complexes,
peaks due to C2dN (157.7-176.5 ppm) and C3a (116.7-
1
122.8 ppm) were recognized. Both H and 13C{1H} NMR
spectra of compounds 1 and 6 exhibit two sets of signals in
ratios of 2:1 and 1:2, respectively, derived from the cis and
trans isomers. Characteristic doublets of the C5 protons for
the trans complexes are low-field-shifted from those for the
appropriate cis forms.
(33) Bokach, N. A.; Khripoun, A. V.; Kukushkin, V. Y.; Haukka, M.;
(34) Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.; Orpen A.
Pombeiro, A. J. L. Inorg. Chem. 2003, 42, 896.
G.; Taylor, R. J. Chem. Soc., Perkin Trans. 1987, 2, S1.
8328 Inorganic Chemistry, Vol. 46, No. 20, 2007

Cycloaddition of Oxazoline N-Oxides to Nitriles
Figure 5. Thermal ellipsoid view of complex 2 with an atomic numbering
scheme. The only RR enantiomer from the RR/SS pair is shown, and thermal
ellipsoids are drawn at 50% probability.
Figure 4. Thermal ellipsoid view of complex 1 with an atomic numbering
scheme. The only RR enantiomer from the RR/SS pair is shown, and thermal
ellipsoids are drawn at 50% probability.
to the typical N-C single bonds. In 1 and 2, both asymmetric
atoms C3a in the heterocyclic ligands have the same config-
uration (RR and SS in the enantiomeric mixture of the
complexes), while in 5 and 9, two ligands exhibit different
configurations (RS). In 1, the {N1C1O1N2C6} planes of two
cyclic ligands are oriented with a 74.65(8)° angle to each
other to minimize steric repulsion. In 2, the torsion angle
between such planes is less [i.e., 24.8(3)°], and in centrosym-
metric 5 and 9, the {N1C1O1N2C6} planes are coplanar.
Stereochemistry of the 1,3-DCA. CA to the nitrile ligands
in the starting complexes, in principle, could give the
heterocyclic ligands having RR, SS, and RS configurations
of the C3a and C′3a atoms. We observed that the stereo-
selectivity of these reactions is different depending on the
R′ group in the complexed nitrile dipolarophiles. Thus, 1,3-
DCA of nitrones C and D to the nitrile ligands in cis/trans
mixtures of the [PtCl2(MeCN)2] complex proceeds diaste-
reoselectively and leads to cis/trans mixtures of 1 or 6,
respectively. The NMR spectra of the products display two
sets of peaks corresponding to enantiomeric mixtures of the
cis and trans complexes (see above and also the Experimental
Section). It was also detected that during the reactions a ratio
between cis and trans isomers has been changed from 5:1 in
the starting complex [PtCl2(MeCN)2] to 2:1 in 1 and 1:2 in
6, correspondingly. These mixtures were not separated by
chromatography because of the very close retention indexes
of the isomers, and ratios between isomers were verified by
1H NMR integration.
Figure 6. Thermal ellipsoid view of complex 5 (a mixture of RS/SR
enantiomers) with an atomic numbering scheme. Thermal ellipsoids are
drawn at 50% probability. The CDCl3 solvent has been omitted for clarity.
1,3-DCA of nitrones C and D to EtCN in trans-[PtCl2-
(EtCN)2] also occurs diastereoselectively and in the cases
of 2 and 7 brings about the formation of enantiomers showing
a sole set of signals in the NMR spectra. The X-ray
diffraction data for complex 2 (Figure 5) indicate that the
C3a atoms of both dihydrooxazolo-1,2,4-oxadiazole ligands,
similarly to 1, have the same configuration. The NMR spectra
of 3 and 7 (the latter obtained in the reaction between C
and D and pure trans-[PtCl2(PhCH2CN)2]) also favor the
diastereoselectivity of the CA. It is worthwhile mentioning
that in the case of the PtII complex with the push-pull nitrile,
i.e., trans-[PtCl2{(CH2)5NCN}2], another pair of enantiomers
is formed in 1,3-DCA. The X-ray data for 5 (Figure 7) show
that the C3a atoms of the heterocyclic ligands have the RS
configuration. In 5 and 10, a different configuration (R and
S) of two bicyclic moieties is supported by NMR data (see
above).
In CA, the change in the proportion between the cis and
trans isomers in solution occurs as a result of the thermal
cis-to-trans isomerization; the latter proceeds in accordance
with the isomerization principle1b,35 for square-planar com-
plexes. Complex cis-1 has been structurally characterized
(Figure 4), and the X-ray data show that in the mixture of
enantiomeric complexes both C3a-asymmetric atoms in the
heterocycles formed and, consequently, the dihydrooxazolo-
1,2,4-oxadiazoles have the same configuration (RR and SS).
In the case of the benzonitrile complexes, CA does not
occur diastereoselectively and the NMR spectra display a
few sets of resonances due to a mixture of diastereomers
(RR/SS/RS). An X-ray study for 9 (Figure 6) verified different
(35) Kukushkin, V. Yu. Russ. J. Inorg. Chem. (Engl. Transl.) 1988, 33,
1085 and references cited therein.
Inorganic Chemistry, Vol. 46, No. 20, 2007 8329

Makarycheva-Mikhailova et al.
dihydrooxazolo-1,2,4-oxadiazoles derived from 1,3-DCA to
the so-called push-pull nitrile (C5H10)NCtN are strongly
bound to the PtII center. They were liberated only under
prolonged heating (5 days at 50 °C) of their MeCN solutions
with en or with NH2CH2CH2NHCH2CH2NH2. However,
under these conditions the heterocycles are not stable, and
they were decomposed right after liberation to give a mixture
of yet unidentified products.
In the liberation reactions, the known32 complex [Pt(en)2]-
(Cl)2 is formed as the other product along with the free
ligand. The hydrophilic complex [Pt(en)2](Cl)2 and the excess
of en were separated from the hydrophobic heterocycle upon
washing of the residue (R ) Ph) or the reaction mixture (R
) Me, Et, CH2Ph) with water.
After the separation, the dihydrooxazolo-1,2,4-oxadiazoles
were subject to 1H and 13C{1H} NMR monitoring in CDCl3
and the same sample was additionally analyzed by ESI-MS.
These data are given in the Experimental Section, and they
unequivocally confirm the decoordination of the heterocycles
and support their formulation. Thus, ESI+-MS spectra display
peaks that can be attributed to [M + H]+ or [M + Na]+. 1H
and 13C{1H} NMR spectra contain one set of signals; in 1H
NMR, C5 protons emerge as two doublets in the ranges of
3.22-3.64 and 3.66-3.73 ppm. In 11-18, 13C{1H} NMR
spectra show peaks from C2dN (162.5-168.4 ppm) and C3a
(121.2-124.6 ppm) atoms.
Figure 7. Thermal ellipsoid view of complex 9 (a mixture of RS/SR
enantiomers) with an atomic numbering scheme. Thermal ellipsoids are
drawn at 50% probability. The solvent molecule CDCl3 has been omitted
for clarity.
enantiomers (R and S) of the dihydrooxazolo-1,2,4-oxadia-
zole ligands. The absence of stereoselectivity for [PtCl2-
(PhCN)2] is probably due to intra/intermolecular interactions
of the phenyl ring, or it can be rationalized by the least steric
hindrance of Ph36 among other R′ groups of the series.
Ligand Liberation and Characterization of the Free
Heterocycles. In the past few years, several methods for
liberation of imines from their PtII complexes have been
developed, and they are based on displacement with an
excess of diphosphines37 or thiourea.38 We observed that the
newly formed heterocyclic ligands in 1-10 are so strongly
bound to the PtII center that liberation cannot be achieved
even with 1,2-bis-(diphenylphosphino)ethane. However, we
succeeded in releasing the ligands for all complexes besides
Final Remarks
The reaction described in this Article is the first example
of the CA between oxazoline N-oxides and nitriles, and it
can be applied to the direct synthesis performed under mild
conditions and using easily prepared PtII compounds of the
previously inaccessible families of 2,3a-disubstituted 5,6-
dihydro-3aH-[1,3]oxazolo[3,2-b][1,2,4]oxadiazoles and their
metal complexes. The reaction has a general character, and
it was successfully employed to various activated (with
acceptor groups, e.g., Ph) and nonactivated (with donor
groups, e.g., Me) nitriles RCN and even to the so-called push-
pull species [R ) N(CH2)5].
two (i.e., 5 and 10), and the free C3a
enantiomeric
R/S
dihydrooxazolo-1,2,4-oxadiazoles were liberated by treatment
with excess en in CH2Cl2 for 1 day at 20-25 °C (for R′ )
Me, Et, CH2Ph) and at 50 °C (for R′ ) Ph) (Scheme 1, route
II). In the latter case, the heterocyclic ligands are strongly
bound in complexes 4 and 9, and their liberation should be
performed at the higher temperature. Under these conditions,
the free dihydrooxazolo-1,2,4-oxadiazoles are not stable, and
therefore they were isolated only in moderate yields (15%
for 14 and 33% for 18). In the other cases, the ligands were
obtained in 55-86% yields. In complexes 5 and 10, the
The presence of the PtII center at the nitrile group was
found to be essential for the reactivity. Indeed, even the rather
electron-deficient nitrile PhCN in the uncomplexed form does
not react with the oxazoline N-oxides, while endeavors to
conduct this reaction under more drastic conditions failed
because of the well-known18,20,21 thermal instability of
oxazoline N-oxides, resulting in their degradation in advance
of the attempted CA.
In accordance with our previous theoretical calculations,
the role of the PtII center in the normal electron-demand CA
reaction15,16 comes to selectiVe coordination of the dipolaro-
phile RCN to a Pt center, and this complexation significantly
lowers the HOMOdipole-LUMOdipolarophile gap between the
reactants, thus facilitating the interplay. Hence, involvement
of a soft and kinetically inert Pt metal center, which reacts
selectively with the dipolarophile and does not affect the
dipole, is crucial for these CAs. The skeptical reader,
however, may feel some dissatisfaction with the use of the
Pt starting material, which makes the suggested synthesis
(36) Tolman, C. A. Chem. ReV. 1977, 77, 313.
(37) (a) Gushchin, P. V.; Bokach, N. A.; Luzyanin, K. V.; Nazarov, A.
A.; Haukka, M.; Kukushkin, V. Yu. Inorg. Chem. 2007, 46, 1684. (b)
Bokach, N. A.; Kukushkin, V. Yu.; Haukka, M.; Frau´sta da Silva, J.
J. R.; Pombeiro, A. J. L. Inorg. Chem. 2003, 42, 3602. (c) Michelin,
R. A.; Mozzon, M.; Berin, P.; Bertani, R.; Benetollo, F.; Bombieri,
G.; Angelici, R. J. Organometallics 1994, 13, 1341. (d) Michelin, R.
A.; Belluco, U.; Mozzon, M.; Berin, P.; Bertani, R.; Benetollo, F.;
Bombieri, G.; Angelici, R. J. Inorg. Chim. Acta 1994, 220, 21. (e)
Michelin, R. A.; Mozzon, M.; Bertani, R.; Benetollo, F.; Bombieri,
G.; Angelici, R. J. Inorg. Chim. Acta 1994, 222, 327.
(38) Kaplan, S. F.; Kukushkin, V. Yu.; Pombeiro A. J. L. J. Chem. Soc.,
Dalton Trans. 2001, 3279.
8330 Inorganic Chemistry, Vol. 46, No. 20, 2007

Cycloaddition of Oxazoline N-Oxides to Nitriles
of 2,3a-disubstituted 5,6-dihydro-3aH-[1,3]oxazolo[3,2-b]-
[1,2,4]oxadiazoles rather expensive. We still believe that the
PtII-mediated CA is so far the only route to these types of
heterocycles, and for a while, we should be satisfied just
with achieving these compounds by any means. In addition,
the conventional recycling39 of Pt might strongly reduce all
expenses associated with this two-step synthetic transforma-
tion.
05-03-32140, and 06-03-32065). V.Yu.K. additionally thanks
the Scientific Council of the President of the Russian
Federation (Grant MK-1040.2005.3), the Government of St.
Petersburg (Grant 46/06), and the Academy of Finland for
support of the cooperation with the University of Joensuu
(Grant 112392). The authors are grateful to E. Podolskaya
for experimental assistance.
Supporting Information Available: Crystallographic data in
CIF format. This material is available free of charge Via the Internet
at http://pubs.acs.org.
Acknowledgment. The authors are very much obliged
to the Russian Fund for Basic Research (Grants 05-03-32504,
(39) For a review, see: Nakahiro, Y. Trans. Mater. Res. Soc. Jpn. 1994,
18A, 167; Chem. Abs. 1995, 123, 89761.
IC701133B
Inorganic Chemistry, Vol. 46, No. 20, 2007 8331