E. Villemin et al. / Tetrahedron Letters 52 (2011) 5140–5144
5143
divalent cations or two nitrate anions for the trivalent lanthanides.
Species with a residual solvent molecule were observed for the
L1:M complexes. This solvent molecule is certainly present to fulfill
the coordination sphere of the metallic cation. Upon increasing the
tube lens voltage we observed the disappearance of these species in
favor of the corresponding L1:M complexes. Interestingly, the pre-
dominant species for all tested cations is a monochelated complex
(i.e., L1:M) except for the trivalent cations La3+ and Ce3+ for which a
bischelated complex is observed (i.e., L2:M). Although a detailed
structural investigation would be required to explain this observa-
tion, it is likely that the size of the metallic core plays an important
role. Indeed, the ionic radius for La3+ and Ce3+ is somewhat larger
(ꢀ120 pm) than that of the other metals (ꢀ110 pm). The same
observation is made when comparing complexes with Ca2+
(ꢀ110 pm) to the other divalent complexes (ꢀ90 pm). The larger
the metal cation, the easier it is to add a second ligand to the coor-
dination sphere. The nature of the ligand should also play a role,
since globally, the percentages of L2:M complexes versus L1:M are
systematically higher for 5 as compared to 8.
8, and computational details) associated with this article can be
References and notes
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BocaRaton, 2000; (b) Kukhar, V. P.; Hudson, H. R. Aminophosphonic,
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Ltd: Chichester, 2000.
2. (a) Mao, J.-G. Coord. Chem. Rev. 2007, 251, 1493–1520; (b) Kafarski, P.; Lejczak,
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Green, J. R. J. Med. Chem. 2002, 45, 3721–3738; (e) Vioux, A.; Le Bideau, J.;
Mutin, P.M.; Leclercq, D. Hybrid Organic-Inorganic Materials Based On
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Anorg. Allg. Chem. 2008, 634, 1836–1838.
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J.; Simonnin, M.-P. Can J. Chem. 1988, 66, 391–396; (c) Lis, S.; Pawlicki, G. J.
Lumin. 2010, 130, 832–838.
We have performed competition experiments considering
either two ligands versus one given cation or two cations versus
5. (a) Robiette, R.; Defacqz, N.; Peeters, D.; Marchand-Brynaert, J. Curr. Org. Synth.
2005, 2, 453–477; (b) Monbaliu, J.-C.; Villemin, E.; Elias, B.; Marchand-
Brynaert, J. Target in Heterocyclic Systems (THS) (Attonasi, O. A.; Spinelli, D.;
Eds), 2010, 14.; (c) Monbaliu, J.-C.; Marchand-Brynaert, J. J. Org. Chem. 2010, 75,
5478–5486; (d) Monbaliu, J.-C.; Tinant, B.; Peeters, D.; Marchand-Brynaert, J.
Tetrahedron Lett. 2010, 51, 1052–1055; (e) Monbaliu, J.-C.; Marchand-Brynaert,
J. Synthesis 2009, 1876–1880.
6. (a) Fringuelli, F.; Taticchi, A. The Diels–Alder Reaction; John Wiley & Sons, 2002;
(b) Boger, D. L.; Weinreb, S. M. In Hetero Diels–Alder Methodology in Organic
Synthesis; Academic Press, Marcourt Brace Jovanovich Publishers, 1987; Vol. 47,
7. (a) Robiette, R.; Marchand-Brynaert, J.; Peeters, D. J. Mol. Struct.—Theochem.
2002, 587, 159–169; (b) Robiette, R.; Marchand-Brynaert, J.; Peeters, D. J. Org.
Chem. 2002, 67, 6823–6826; (c) Monbaliu, J.-C.; Dive, G.; Marchand-Brynaert,
J.; Peeters, D. J. Mol. Struct.—Theochem. 2010, 959, 49–54.
one given ligand. First,
a mixture of 5 (0.25 mM) and 8
(0.25 mM) in EtOH with 5 equiv of Mn2+ or Zn2+ was analyzed as
above (see Supplementary data). The selectivity of ligands toward
each metal is measured by the ratio of respective complexes de-
tected by ESI-HRMS. We found for Mn2+ and Zn2+, a selectivity of
7.4 and 5.9, respectively, in favor of ligand 5, meaning that the cage
shape allowed better complexation properties. Ligand 5 (0.5 mM)
in EtOH with a mixture of Eu3+ (2.5 equiv) and La3+ (2.5 equiv)
was studied; the selectivity of metals toward the best ligand 5
was 27.5 in favor of Eu3+. This suggests that the hardest metal is
complexed, as expected in the case of O,O-bidentate ligands.
8. Beck, J.; Maton, L.; Habib Jiwan, J.-L.; Marchand-Brynaert, J. Amino Acids 2011,
40, 679–689. and references cited therein.
9. Griffin, C. E.; Daniewski, W. M. J. Org. Chem. 1970, 35, 1691–1693.
Conclusion
10. Protocol for the synthesis of
5 and spectroscopic characterization (see
Supplementary data for compounds 2, 3 and 4). A neat mixture of diene 1
(0.200 g, 1.052 mmol, 1 equiv) and N-phenylmaleimide (0.182 g, 1.052 mmol,
1 equiv) is stirred at 120 °C for 1 h. The reaction is followed by TLC and 31P
NMR. The oily reaction mixture is directly purified by column chromatography
(silica gel: ethyl acetate) to afford a white solid (0.216 g, 56%). Rf = 0.2 (ethyl
Using the stereoselective (H)DA strategy, we have obtained new
phosphonated ligands that are structurally related to DPIP (see
Fig. 1). Their bicyclic framework orientates adequately the P@O
motif (from diene 1) and the neighboring C@O function (from
dienophiles) to enable metal complexation.
As evidenced by ESI-HRMS, both ligands 5 and 8 are able to
make L1:M and L2:M complexes with a large variety of di- and
tri-valent cations. However 5 (bicycle with C–C junction) appeared
6- to 7-fold more powerful than 8 (bicycle with N–N junction), and
selective toward hard M+3 cations.
acetate); mp = 73.3–73.7 °C; 1H NMR (500 MHz, CDCl3):
d 7.44 (ddd,
4
3JH,H = 7.5 Hz and JH,H
=
5JH,H = 2.3 Hz, Ph, 2H), 7.37–7.35 (m, Ph, 3H), 6.16–
3 3
6.15 (m, CH@CH, 1H), 6.01 (dd, JH,H = 9.7 Hz and JH,P = 4.9 Hz, CH@CH, 1H),
4.18–4.09 (m, PO(OCH2CH3)2, 2H), 4.10–4.01 (m, PO(OCH2CH3)2, 2H), 3.35 (dtd,
3
4
3
3JH,P = 26.2 Hz, JH,H = 8.6 Hz and JH,H = 3.5 Hz, 1H), 3.27 (td, JH,H = 9.2 and
2
3
4
3.8 Hz, CH, 1H), 3.20 (dtd, JH,P = 22.0 Hz, JH,H = 6.8 Hz and JH,H = 2.7 Hz, CH,
2
1H), 2.80–2.76 (m, JH,H = 17.1 Hz, CH2, 1H), 2.55–2.51 (m, CH2, 1H), 1.24 (td,
3JH,H = 7.0 Hz and JH,P = 3.0 Hz, PO(OCH2CH3)2, 3H), 1.21 (td, JH,H = 7.0 Hz and
4
3
4JH,P = 3.1 Hz, PO(OCH2CH3)2, 3H); 13C NMR (125 MHz, CDCl3): d 178.34 (s,
3
3
C@O), 175.64 (d, JC,P = 4.8 Hz, C@O), 132.18 (s, Ph), 130.46 (d, JC,P = 11.3 Hz,
C@C), 128.99 (s, Ph), 128.43 (s, Ph), 126.55 (s, Ph), 123.23 (d, JC,P = 9.4 Hz,
C@C), 63.11 (d, JC,P = 6.5 Hz, PO(OCH2CH3)2), 62.17 (d, JC,P = 7.2 Hz,
PO(OCH2CH3)2), 40.66 (d, JC,P = 3.2 Hz, CH), 38.51 (d, JC,P = 5.8 Hz, CH), 34.06
Work is in progress for the development of N-functionalized
derivatives of 3 featuring additional chelating functions.
2
2
2
2
3
1
3
(d, JC,P = 142.2 Hz, CH), 22.10 (s, CH2), 16.23 (d, JC,P = 5.3 Hz, PO(OCH2CH3)2),
16.20 (d, 3JC,P = 4.2 Hz, PO(OCH2CH3)2); 31P NMR (121 MHz, CDCl3): d 25.50; IR:
Acknowledgments
m
3657–3327 (w), 2984 (m), 1782 (C@O, w), 1713 (C@O, s), 1597 (m), 1498 (s),
1442 (w), 1383 (s), 1244 (P@O, s), 1196 (s), 1164 (s), 1049 (s), 1020 (P–O, s),
960 (P–O, s), 750 (s), 692 (s), 659 (s) cmÀ1; HRMS: m/z calcd for C18H21NO5P:
362.1157. Found: 362.1140.
This work was supported by the ARC (Action de Recherche Con-
certée, UCL) Program no. 08/13-009, the PAI (Pôle d’Attraction
Interuniversitaire, Belgium) Program no. P06-27, the Fonds de la
Recherche Scientifique (F.R.S.-FNRS, Belgium) FRFC Grants nos.
2.4555.08 and 2.4502.05, and the Fonds Spécial de Recherche
(FSR) of the Faculty of Medecine (UCL). J.M.-B. and R.R. are senior
research associates of F.R.S.-FNRS. Sabrina Devouge is acknowl-
edged for assistance in preparing the manuscript.
11. Clement, R. A. J. Org. Chem. 1962, 27, 1115–1118.
12. Protocol for the synthesis of
Supplementary data for compounds 6 and 7). A solution of 4-phenyl-4H-
1,2,4-triazole-3,5-dione (0.46 g, 2.63 mmol, 1 equiv), diene (0.50 g,
8 and spectroscopic characterization (see
1
2.63 mmol, 1 equiv), and dichloroethane (3.5 mL) is stirred in a microwave
oven under 500 W irradiation at 120 °C for 30 min. The reaction mixture is
then concentrated under vacuum and purified by column chromatography
(silica gel: toluene, then ethyl acetate) to afford a pale yellow gummy solid
(0.794 g, 83%). Rf = 0.4 (ethyl acetate); mp = 67.5–71.0 °C; 1H NMR (500 MHz,
3
3
CDCl3): d 7.54–7.42 (m, Ph, 5H), 6.11 (dtt, JH,H = 10.3 Hz, JH,H
and JH,P
=
4JH,H = 5.2 Hz
=
4JH,H = 2.2 Hz, CH@CH, 1H), 6.09–6.03 (m, CH@CH, 1H), 4.97 (dddt,
3 4 5
4
2JH,P = 14.7 Hz, JH,H = 4.8 Hz, JH,H = 3.1 Hz and JH,H = 1.5 Hz, 1H), 4.29 (dddd,
Supplementary data
2JH,H = 16.9 Hz, JH,H = 6.7 Hz, JH,P = 3.7 Hz and JH,H = 1.7 Hz, CH2, 1H), 4.07–
3
5
4
2
3
4.16 (m, PO(OCH2CH3)2, 4H), 4.03 (ddq, JH,H = 16.8 Hz, JH,H = 6.7 Hz and
Supplementary data (synthetic protocols for the preparation of
2, 3, 4, 6 and 7 and related spectroscopic analyses, X-ray data of 8,
ESI-HRMS spectra of representative complexes of endo-5, exo-5 and
4JH,H
= =
5JH,H 5JH,P = 2.4 Hz, CH2, 1H), 1.28 (t, JH,H = 7.3 Hz, PO(OCH2CH3)2, 3H),
3
1.27 (t, 3JH,H = 7.0 Hz, PO(OCH2CH3)2, 3H); 13C NMR (125 MHz, CDCl3): d 152.21
(s, C@O), 150.17 (s, C@O), 130.73 (s, Ph), 128.28 (s, Ph), 127.30 (s, Ph), 124.75